【最新2014-2015】补肾抗衰汤对氧化应激所致的秀丽隐杆线虫生育缺陷的影响-医学论文

【最新2014-2015】补肾抗衰汤对氧化应激所致的秀丽隐杆线虫生育缺陷的影响-医学论文 补肾抗衰汤对氧化应激所致的秀丽隐杆线虫生育缺 陷的影响 作者:曹新国, 侯莉莉, 陈军霞, 陆勤 【摘要】 目的:探讨补肾抗衰汤对秀丽隐杆线虫因氧化应激诱导所致生育缺陷的作用。方法:将终浓度为0.33 g/mL的补肾抗衰汤按25%、50%、75%和100%梯度稀释后对L4期线虫培养。应激方式采用紫外线照射,20 J/(m2〃min),、热休克,36 ?, 2 h,和 百草枯(2 mmol/L, 2 h)处理。通过子宫内卵数、卵的大小和传代时间来评价秀丽隐杆线虫的生育能力。结果:野生型N2线虫经过紫外线照射、热休克和百草枯处理后，子宫内卵数、卵的大小均显著减少，传代时间明显增加,过氧化氢酶和过氧化物歧化酶活性被抑制。补肾抗衰汤对野生型线虫没有毒性或其他副作用。高浓度补肾抗衰汤不仅能够减轻由紫外线照射、热休克和百草枯所导致的生育缺陷，而且可以增加过氧化氢酶和超氧化物歧化酶被各种应激抑制的活性。此外，高浓度补肾抗衰汤可以明显恢复突变体线虫受损的生育能力。 结论:氧化应激对生育能力有负面影响，高浓度补肾抗衰汤可明显逆转氧化应激所致的线虫生育缺陷。 【关键词】 补肾抗衰汤; 氧化应激; 生育; 线虫 更多精品文档,欢迎来我主页查询 The reproductive successes of animals and humans depend on a series of careful neuroendocrine events, and the reproduction failure will occur if the timing for any one of these events is disrupted,1,. Under such conditions, animal reproduction will be at risk due to the effects of stress, and the reproductive process controlled by the neuroendocrine 1,. For example, system appears to be the most vulnerable, when dairy cattle are subjected to heat stress, reproductive efficiency declines. Cows under heat stress have reduced development, and impaired embryonic development,2,. Stress can be defined as an event (physical, environmental, psychological, etc.) which significantly challenges the homeostasis of the animals. In mammals, stress impacts on the reproductive axis at the hypothalamus and the pituitary gland,3,. Various stressful conditions have adverse effects on reproduction of animals, and the stress conditions include environmental factors (i.e., temperature, humidity, metals and irradiation), physical factors (i.e., transport, shearing, restraint and strenuous exercise), metabolic factors (i.e., 更多精品文档,欢迎来我主页查询 infection and endotoxins administration), and psychological factors (i.e., isolation, social interactions and mental ,. arithmetic tasks), Caenorhabditis elegans, a classical model organism, is a free living nematode with a nervous system, specialized muscles, and digestive and reproductive systems,6,. The reproductive process has been investigated extensively in C.elegans,, and their reproductive process is modulated by diverse environmental cues,,. Among these environmental cues, environmental stress can affect the reproductive process of nematodes significantly. The data from Coohill et al,10, showed the effects of ultraviolet (UV) irradiation on larval development and fertility. The reproductive process can also be altered by heat stress in nematodes,11,. Electromagnetic nanopulse exposure will be resulted in the decreased fertility of C. elegans by interfering with the fertilization or development,12,. In addition, exposure to heavy metals of lead, silver, nickel and zinc will cause severe defects of brood 更多精品文档,欢迎来我主页查询 size and generation time in exposed nematodes,,. Bushen Kangshuai Tang (BKT), a compound traditional Chinese herbal medicine, has been widely used for clinical treatment of premature ovarian failure (POF). This medicine can alleviate the inhibitory action of excessive androgen on ovarian granulosa cells and regulate the ovarian function by promoting follicular development, increasing the levels of estrogen and progestogen, and improving the ratio of estrogen/androgen. In present study, we provided evidences for the retrieval effect of this medicine on oxidative model. Three parameters had been selected to evaluate the reproductive process, which were eggs in uterus, brood size, and generation time. 1 Materials and methods 1.1 Materials 更多精品文档,欢迎来我主页查询 1.1.1 Preparation of BKT and chemicals BKT consists of nine medicinal herbs: Semen Cuscutae (Tusizi) 15 g, Rhizoma Polygonati Sibirici (Huangjing) 15 g, prepared Radix Rehmanniae (Shudihuang) 15 g, Herba Cynomorii Songarici (Roucongrong) 10 g, Radix Morindae Officinalis (Bajitian) 10 g, Radix Angelicae Sinensis (Danggui) 10 g, Rhizoma Chuanxiong (Chuanxiong) 6 g, Fluoritum (Zishiying) 15 g, and Fructus Schisandrae Chinensis (Wuweizi) 6 g, which were purchased from Pharmacy of Nanjing Maternity and Child Health Care Hospital. The herbs were soaked in 2 000 mL distilled water (DW) for 2 h, and then boiled for 60 min for the first decoction; the second and third decoctions were obtained by adding DW to 1 000 mL each and then boiled for 1 h. After being mixed, the decoction was condensed with water bath to crude drug content 0.33 g/mL and stored at 4 ? until use. All other chemicals were obtained from 1.1.2 C.elegans model All experiments were performed on 更多精品文档,欢迎来我主页查询 hermaphrodite C. elegans. The strains used in the current originally obtained from the Caenorhabditis Genetics Center (Minneapolis, MN, USA). They were maintained on nematode growth medium (NGM) plates and seeded with Escherichia coli OP50 at 20 ? as described by Brenner,17,. nematodes were obtained by collection as described,18,. The modified K medium once (50 mmol/L NaCl, 30 mmol/L KCl, 10 mmol/L NaOAc, pH 5.5),19,. Exposures were performed nematodes with 25%, 50%, 75%, and 100% of examined BKT diluted with M9 buffer. Experiments of all concentrations were repeated 3 times respectively. Approximately 100 nematodes were transferred in 100 μL to each exposure solution in the micropipetter. All exposures were carried out in 20 ? incubator for 2 h in the absent of food. All the administration. 更多精品文档,欢迎来我主页查询 1.2 Methods 1.2.1 Brood size assay The procedure was performed as previously described,15,. Briefly, brood size was assayed by placing exposed or control nematodes onto individual culture plates. The examined nematodes were transferred four times to a new well every 1.5 days, and the total number of eggs released on the plates was scored. At least 20 replicates were performed for statistical purposes. 1.2.2 Eggs in uterus To score the number of eggs in the uterus, the treated or control adult nematodes were individually transferred to a drop of solution containing commercial bleach and 1 mol/L NaOH on a glass slide covered with an agar pad. The bleach solution dissolved the body of the adult nematodes, and eggs were scored immediately under digit optics with a Zeiss microscope. 更多精品文档,欢迎来我主页查询 1.2.3 Generation time assay The experiment was performed as previously described,15,. The generation time refers to the time from day of birth (P0) egg to the first filial generation (F1) egg. At least 20 replicates were performed for statistical purposes. 1.2.4 UV irradiation experiments Approximately 30 at 20 J/(m2〃min) by using a germicidal bulb (254 nm) for 2 hours as described by Murakami et al,20,. All UV irradiation assays were performed at 20 ?, and afterwards further maintained at 20 ?. All assays were replicated more than three times. 36 ? and afterwards further maintained at 20 ?. All assays were replicated more than three times. 更多精品文档,欢迎来我主页查询 larvae were treated with 2 mmol/L paraquat solution for 2 h at 20 ?. All assays were replicated more than three times. 1.2.7 Superoxide dismutase and catalase activities The treated or control adult nematodes were used for the assay of superoxide dismutase (SOD) and catalase (CAT) activities as previously described,21,. The CAT activity was estimated following the method of Abei,22,. The decrease in absorption was measured spectrophotometrically at 240 nm. An extinction coefficient of 43.6/(mol〃cm) was used to determine the enzyme activity. The SOD activity was measured by using the kit from Randox Laboratories following the manufacturer’s protocol. The data were the summary of three trials. 1.3 Statistical analysis All data in this article were followed by a Dunnett’s t test was used to determine the significant differences between the groups. P value ,0.05 更多精品文档,欢迎来我主页查询 was considered statistical difference, P value ,0.01 was considered statistical significant difference. 2 Results 2.1 Administration of BKT did not affect the reproduction of wild of BKT administration on the reproductive process of size, and generation time were examined after 2 h administration of 25%, 50%, 75%, and 100% BKT on decreases of egg number in uterus, brood size, and generation time could be observed in nematodes after exposed to different concentrations of BKT as compared with the control. Usually, egg number in uterus and brood size reflect the reproductive capacity, whereas a longer generation time indicates a low reproductive speed. Therefore, administration of BKT did not enhance or suppress the 更多精品文档,欢迎来我主页查询 elegans. That is, our data suggest that administration of BKT did not cause toxic or altered effects on animals’ reproduction. 2.2 Effects of administration of BKT on reproductive defects induced by UV irradiation in C. elegans In C. elegans, UV irradi cause oxidative stress,,. Considering the possibility that the oxidative stress may negatively regulate the reproductive process, we next examined whether the administration of BKT could retrieve the reproductive defects induced by UV irradiation. As shown in Figure 2, after UV irradiation at 20 J/(m2〃min), the egg number in uterus and brood size of exposed nematodes were significantly decreased as compared with the control (P 0.01), while the generation time was significantly increased as compared with the control (P 0.01). Again, administration of 75% and 100% of BKT would markedly increase the egg number in uterus (75%, P 0.05; 100%, P 0.01) and brood size (P 0.01), and reduce the generation time (75%, P 0.05; 100%, P 0.01) as compared with UV irradiation. However, administration of BKT at 25% 更多精品文档,欢迎来我主页查询 and 50% could only moderately alter the reproductive of egg number in uterus, brood size and generation time induced by UV irradiation could be effectively alleviated by administration of 75% of BKT. The defects of egg number in uterus, brood size, and generation time induced by UV irradiation could be effectively alleviated by administration of 100% of BKT. Therefore, administration of BKT at higher concentrations could largely retrieve the reproductive defects induced by UV irradiation in C. elegans. 2.3 Effects of administration of BKT in reproductive defects ther investigated whether the administration of BKT could also largely retrieve brood size, and increased generation time as compared with administration of high concentrations (75% and 100%) of BKT to C. elegans resulted in significant decreases of egg 更多精品文档,欢迎来我主页查询 number in uterus and brood size, and increase of generation 0.05; 100%, P 0.01). In contrast to this, administration of 25% and 50% of BKT would not significantly alter the egg number, brood size, and generation time of nematodes. Therefore, administration of 75% and 100% of BKT could also largely recover the nematodes. 2.4 Effects of administration of BKT on reproductive defects induced by paraquat treatment in C. elegans Paraquat treatment causes oxidative stress through a metabolically catalyzed reaction to result in depletion of (NADPH) and production of ROS, primarily superoxide anions,27,. As shown in Figure 4, treatment with 2 mmol/L paraquat solution caused obvious reduction of egg number and brood size and elongation of generation time as compared with the control (P 0.01). Following paraquat treatment, administration of 75% and 100% of BKT could 更多精品文档,欢迎来我主页查询 significantly alleviate the defects of egg number in uterus (75%, P 0.05; 100%, P 0.01), brood size (P 0.01), and generation time (P 0.01) induced by paraquat exposure, whereas administration of 25% and 50% of BKT would not have obvious effects on the reproductive process in par number in uterus, brood size, and generation time induced by paraquat treatment could be effectively alleviated by administration of 75% of BKT by approximately 65.2%, 55.4%, and 62.5%, respectively. In addition, the defects of egg number in uterus, brood size, and generation time induced by paraquat treatment could be effectively alleviated by administration of 100% of BKT by approximately 83.5%, 77.2%, and 81.6%, respectively. Therefore, administration of high concentrations of BKT would largely retrieve the 2.5 Administration of BKT after stress exposure altered the CAT and SOD activities in C. elegans CAT, acting in concert with SOD, belongs to the major defense enzymes against superoxide radicals, and activities of CAT and SOD are 更多精品文档,欢迎来我主页查询 directly linked to oxidative stress,28, 29,. To examine whether the retrieval effects of BKT on reproductive defects paraquat treatment are through alleviating the damage from oxidative stress, we further investigated the activity changes of CAT nematodes. As shown in Figure 5, UV irradiation, ment all caused significant decreases of CAT and SOD activities as compared with the control, suggesting the occurrence of severe damage from oxidative stress. Moreover, administration of 50%, 75%, and 100% of BKT could significantly increase the CAT and SOD 0.01. SOD: 50%, P 0.05; 75% and 100%, P 0.01), and ed nematodes without BKT administration. Furthermore, the decreases of CAT by administration of 50% BKT by approximately 27.1%, 41.5%, and 38.2%, respectively, and the decreases of SOD 更多精品文档,欢迎来我主页查询 by administration of 50% BKT by approximately 44.6%, 39.3%, and 42.6%, respectively. The decreases of CAT ac by administration of 75% of BKT by approximately 47.9%, 56.9%, and 58.3%, respectively, and the decreases of SOD ed, and by administration of 75% BKT by approximately 64.6%, 66.4%, and 65.9%, respectively. In addition, the decreases of atodes could be effectively alleviated by administration of 100% of BKT by approximately 63.5%, 71.3%, and 79.4%, respectively, and the decreases of SOD vered by administration of 100% of BKT by approximately 83.6%, 84.2%, and 82.2%, respectively. Therefore, administration of high concentrations of BKT could largely recover the 更多精品文档,欢迎来我主页查询 and paraquat treatment by alleviating the damage from the oxidative stress. 2.6 Administration of BKT largely rescued the reproductive complex ? of the electron transport chain, and mutation of this gene will cause elevated levels of superoxide and short lifespan,30, phenotypes consistent with elevated oxidative stress such as sensitivity to the superoxide generator paraquat or high oxygen, which provides a useful tool for testing compounds or medicines for antioxidant properties,31, 32,. As shown in defects with significant reduction of egg number in uterus and brood size, and elongation of generation time as the important role of elevated levels of superoxide in inducing reproductive defects. In addition, we observed that administration of 50%, 75%, and 100% of BKT all would noticeably increase the egg number in uterus and brood size 更多精品文档,欢迎来我主页查询 without BKT administration (P 0.01), whereas administration of 25% of BKT would not obviously affect the reproductive recovered by 41.2%, 70.1%, and 89.3%, respectively, after administration of 50% BKT, and the brood size of mmutant nematodes could be alleviated by 38.4%, 69.4%, and 90.7%, respectively, after administration of 75% BKT, and retrieved by 52.4%, 72.1%, and 85.7%, respectively, after administration of 100% nematodes. Therefore, administration of high concentrations of BKT largely rescued the reproductive defects formed in Figure 1 Effects of BKT administration on egg number in nematodes 更多精品文档,欢迎来我主页查询 nematodes with 25%, 50%, 75%, and 100% of examined BKT diluted with M9 buffer. At least 20 replicates were performed for assay of egg number in uterus, brood size and generation Dunnett’s t test was used to determine the significance of the differences between the groups. Data are expressed as x〒s, n=30. Figure 2 Retrieval effects of BKT administration on egg number in uterus, brood size and generation time in NGM plates without food at 20 J/(m2〃min). All UV irradiation assays were performed at 20 ?, and afterwards 更多精品文档,欢迎来我主页查询 further maintained at 20 ?. Exposures were performed for 2 100% of examined BKT diluted with M9 buffer. All assays were replicated more than three times. Data are expressed as x〒s, n=30. *P 0.05, **P 0.01, vs control group; ?P 0.05, ??P 0.01, vs UV group. Figure 3 Retrieval effects of BKT administration on egg number in uterus, brood size and generation time matodes grown on 20 ? were heat stressed for 2 h at 36 ? and afterwards further maintained at 20 ?. Exposures were 50%, 75%, and 100% of examined BKT. All assays were replicated more than three times. Data are expressed as x〒s, n=30. *P 0.05, **P 0.01, vs control group; ?P 0.05, ??P 更多精品文档,欢迎来我主页查询 0.01, vs HS group. Figure 4 Retrieval effects of BKT administration on egg number in uterus, Approxima mmol/L paraquat solution for 2 h and survival at 20 ?. nematodes with 25%, 50%, 75%, and 100% of examined BKT diluted with M9 buffer. All assays were replicated more than three times. Data are expressed as x〒s, n=30. *P 0.05, **P 0.01, vs control group; ?P 0.05, ??P 0.01, vs paraquat group. Figure 5 Effects of BKT administration on CAT and SOD 更多精品文档,欢迎来我主页查询 nematodes irradiated on NGM plates without food at 20 J/(m2〃min) at 20 ?, or heat stressed for 2 h at 36 ?, or treated with 2 mmol/L paraquat solution for 2 h and survival at 20 ?. Ex nematodes with 25%, 50%, 75%, and 100% of examined BKT diluted with M9 buffer. All assays were replicated more than three times. Data are expressed as x〒s, n=30. *P 0.05, **P 0.01, vs control group; ?P 0.05, ??P 0.01, vs UV group; ?P 0.05, ??P 0.01, vs HS group; ?P 0.05, ??P 0.01, vs paraquat group. Figure 6 Administration of BKT could retrieve the defects of egg number 更多精品文档,欢迎来我主页查询 mutant nematodes N2, wil and 100% of examined BKT diluted with M9 buffer. All assays were replicated more than three times. Data are expressed as x〒s, n=30. *P 0.05, **P 0.01, vs control group; ?P 0.05, 3 Discussion 3.1 Occurrence of oxidative stress is one of the important reasons to induce reproductive defects in C. elegans Previous studies have suggested that stress exposure will induce severe reproductive defects in exposed animals. For example, 更多精品文档,欢迎来我主页查询 ovarian follicles in animal models, and exposure to this toxin at the work place is linked closely to an increase in the incidence of early menopause and infertility in female 33,. Exposure to polycyclic aromatic hydrocarbons, workers, major toxic components of cigarette smoke, will cause follicle destruction in experimental animals,34,. Among the investigated stresses capable of inducing reproductive defects, oxidative stress may play an important role in negatively regulating the reproductive process. Oxidative stress has been supposed to be one of the possible mechanisms of ovarian damage,35,. In the present study, we provide evidence to support the important role of oxidative stress in negatively regulating treatment can cause oxidative stress in nematode C. elegans,,. In addition, paraquat was explored to further investigate the role of oxidative stress in reproduction control as it is known to generate superoxide anions in vivo, and to be toxic to C. elegans,26,. As indicated by the data from Figure 2 to Figure 4, UV irradiation ,20 J/(m2〃min),, 更多精品文档,欢迎来我主页查询 aquat treatment (2 mmol/L, 2 h) all significantly reduced the egg number in uterus and brood size, and increased the generation time of treatment, and paraquat treatment significantly decreased markedly decrease the egg number in uterus and brood size, and prolong the generation time a reduced the activities of CAT and SOD in mutant nematodes (data not shown). Therefore, our data suggest that the oxidative stress can negatively regulate the reproductive process in exposed nematodes. In C. elegans, some other evidence can further support our conclusion to different degrees. Exposure to heavy metal of barium would cause severe defects of brood size and generation time, as well as obvious decrease of CAT and SOD activities,21,. Knockdown of K10C2.4, which encodes a 更多精品文档,欢迎来我主页查询 homolog of fumarylacetoacetate hydrolase, produces the phenotypes of impaired fertility and activation of oxidative stress,36, germ cell apoptosis throu pathway in nematodes,37,. Moreover, mutation of the Saccharomyces cerevisiae NDI 1 gene will increase the production of damaging reactive oxygen species, and expression of this gene in C. elegans can produce marked improvements in animal reproduction,38,. 上一页1 2下一页 3.2 Administration of BKT can largely retrieve the reproductive defects induced by oxidative stress POF may be caused by any process which can reduce the number of oocytes within the ovary,39,. Environmental factors, together with autoimmune genetic aberrations, ovarian damage, and iatrogenic admage following interventions as in malignancies, induce the POF in human beings,40,. Especially, the important role of oxidative stress in regulating POF has been already suggested by some studies,41, 42,. Loss of Nrf2 function may block the detoxification of 更多精品文档,欢迎来我主页查询 increase the oxidative stress,41,. In addition, progressive external ophthalmoplegia patients with the mutation of POLG, which encodes the DNA polymerase γ, can develop POF, and mouse and yeast models with this mutation show enhanced amounts of oxidative lesions and increased mtDNA damage,42,. BKT is a compound traditional Chinese herbal medicine nourishing qi, blood, yin of kidney for clinical alleviation of POF. This medicine may play a regulatory action on ovarian function by activating endocrine and autocrine pathways. Some useful components may be contained in this medicine, and these components may be further identified and explored for the future clinical treatment. The antioxidative activity of flavonoids from Semen Cuscutae was confirmed by adopting spectrometer determining the scavenging action of flavonoids on the free radicals,43,. Prepared Radix Rehmanniae can increase activities of SOD and nitric oxide synthase (NOS) in brain tissue against oxidation and delay senescence process,44,. Phenylethanoid glycosides (PEG) extracted from Cistanche salsa exhibit stronger antioxidant capacity as 更多精品文档,欢迎来我主页查询 compared with the positive control vitamin E,45,. Morinda officinalis How water extract had antioxidant activity in vegetable oil, and as the addition increases, antioxidant activity becomes better,46,. Radix Angelicae Sinensis, Rhizoma Ligustici Chuanxiong and Schisandra sphenanthera Rehd. et Wils extracts all showed significant antioxidative effects,47, 48,. We will further study the single herb extracts from Semen Cuscutae, Rhizoma Polygonati Sibirici, prepared Radix Rehmanniae, etc. to try to find out the more useful active components. In the current work, we provide several lines of evidence to indicate the important function of BKT in alleviating oxidative organism C. elegans. Firstly, administration of BKT could effectively alleviate the reproductive defects induced by UV administration of BKT could significantly increase the CAT and SOD activities suppressed by UV irradiation, aquat treatment as compared with the control; thirdly, administration of BKT could largely recover 更多精品文档,欢迎来我主页查询 nematodes. Therefore, administration of BKT can largely fects in C. elegans. These observations are useful for our understanding the effective function of BKT in alleviating the POF. In the clinical treatment, the combination of 1 000 U of the POF treatment,49, cataract and retinopathy in other animal models,35,. Therefore, besides the efforts to produce enzyme activators sphate uridyltransferase activity or enhance alternative pathways, or gene therapy, the combination of BKT administration or preventions will provide us a new clue for clinical POF retrieval. 更多精品文档,欢迎来我主页查询 4 Acknowledgements Strains used in this work were provided by the Caenorhabdits Genetics Center (funded by the NIH, National Center for Foundation from Research Resource, USA). This work was supported by the grant from the Nanjing Scientific and Technical Plan 【参考文献】 1 Moberg GP. How behavioral stress disrupts the endocrine control of reproduction in domestic animals. J 2 Jordan ER. Effects of heat stress on reproduction. J Dairy 3 Tilbrook AJ, Turner AI, Clarke IJ. Effects of stress on glucocorticoids and sex differences. Rev Reprod. 2000; 5(2): 更多精品文档,欢迎来我主页查询 4 Dobson H, Ghuman S, Prabhakar S, Smith R. A conceptual model of the influence of stress on female 5 Maeda K, Tsukamura H. The impact of stress on reproduction: Are glucocorticoids inhibitory or protective to gonadotropin secretion? Endocrinology. 2006; 147(3): 6 Wang Y, Xie W, Wang DY. Transferable properties of Caenorhabditis elegans. Environ Toxicol Chem. 2007; 26(11): 7 Desai C, Garriga G, McIntire SL, Horvitz HR. A genetic pathway for the development of the Caenorhabditis elegans 8 Crittenden SL, Bernstein DS, Bachorik JL, Thompson BE, Gallegos M, Petcherski AG, Moulder G, Barstead R, Wickens rols 更多精品文档,欢迎来我主页查询 germline stem cells in Caenorhabditis elegans. Nature. 2002; 9 Kimble JE, White JG. On the control of germ cell development in Caenorhabditis elegans. Dev Biol. 1981; 81(2): 10 Coohill T, Marshall T, Schubert W, Nelson G. Ultraviolet nematode Caenorhabditis elegans. Mutat Res. 1988; 11 Lithgow GJ, White TM, Hinerfeld DA, Johnson TE. ele 12 Bojjawar T, Jalari M, Aamodt E, Ware MF, Haynie DT. Effect of electromagnetic nanopulses on C. elegans fertility. caused by lead exposure exhibit transferable properties from 更多精品文档,欢迎来我主页查询 exposed parents to their progeny in Caenorhabditis elegans. 14 Wang DY, Yang P. Silver exposure causes transferable defects of phenotypes and behaviors in nematode 15 Wang D, Wang Y. Nickel sulfate induces numerous defects in Caenorhabditis elegans that can also be transferred to progeny. Environ Pollut. 2008; 151(3): 16 Wang DY, Shen LL, Wang Y. The phenotypic and behavioral defects can be transferred from zinc exposed nematodes to their progeny. Environ Toxicol Pharmacol. 17 Brenner S. The genetics of Caenorhabditis elegans. 18 Donkin SG, Williams PL. Influence of developmental stage, salts and food presence on various end points using 更多精品文档,欢迎来我主页查询 Caenorhabditis elegans for aquatic toxicity testing. Environ 19 Williams PL, Dusenbery DB. Aquatic toxicity testing using the nematode Caenorhabditis elegans. Environ Toxicol 20 Murakami S, Johnson TE. A genetic pathway conferring life extension and resistance to UV stress in Caenorhabditis elegans. Genetics. 1996; 143( 21 Wang DY, Wang Y. Phenotypic and behavioral defects caused by barium exposure in nematode Caenorhabditis elegans. Arch Environ Contam Toxicol. 2008; 54(3): 22 Abei H. Catalase in vitro. Meth Enzymol. 1984; 105(2): life and increased stress resistance. Neurobiol Aging. 1999; 更多精品文档,欢迎来我主页查询 24 Ye H, Ye B, Wang D. Trace administration of vitamin E duced memory deficits in nematode Caenorhabditis elegans. Neurobiol Learn Mem. 2008; 90(1): 25 Springer W, Hoppe T, Schmidt E, Baumeister R. A Caenorhabditis elegans Parkin mutant with altered solubility teotoxic stress. 26 Sampayo JN, Olsen A, Lithgow GJ. Oxidative stress in Caenorhabditis elegans: protective effects of superoxide dismutase/catalase mimetics. Aging Cell. 2003; 2(6): 27 Halliwell B, Gutteridge JMC. Free radicals in biology and medicine. 3rd ed. Oxford: Oxford University Press. 1999. 28 Duong TT, Antao S, Ellis NA, Myers SJ, Witting PK. Supplementation with a synthetic polyphenol limits oxidative 更多精品文档,欢迎来我主页查询 stress and enhances neuronal cell viability in response to 29 Ansari MA, Roberts KN, Scheff SW. Oxidative stress and modification of synaptic proteins in hippocampus after traumatic brain injury. Free Radic Biol Med. 2008; 45(4): 4 30 Lin YT, Hoang H, Hsieh SI, Rangel N, Foster AL, Sampayo JN, Lithgow GJ, Srinivasan C. Manganousion supplementation accelerates wild type development, enhances stress resistance, and rescues the life span of a mutant. Free Radic Biol 31 Ishii N. Oxidative stress and aging in Caenorhabditis 32 Melov S, Ravenscroft J, Malik S, Gill MS, Walker DW, Clayton PE, Wallace DC, Malfroy B, Doctrow SR, Lithgow GJ. 更多精品文档,欢迎来我主页查询 33 Yu X, Kamijima M, Ichihara G, Li W, Kitoh J, Xie Z, causes ovarian dysfunction by damaging primordial follicles and their oocytes in female rats. Toxicol Appl Pharmacol. 34 Mattison DR. Morphology of oocyte and follicle destruction by polycyclic aromatic hydrocarbons in mice. Toxicol Appl Pharmacol. 1 Pathophysiology of impaired ovarian function in 36 Fisher AL, Page KE, Lithgow GL, Nash L. The Caenorhabditis elegans K10C2.4 gene encodes a member of the fumarylacetoacetate hydrolase family: a Caenorhabditis elegans model of type ? tyrosinemia. J Biol Chem. 2008; 更多精品文档,欢迎来我主页查询 germ cell apoptosis by a p53 independent pathway in Caenorhabditis elegans. Cell Death Differ. 2006; 13(12): Expression of Ndi 1p, an alternative NADH: ubiquinone oxidoreductase, increase mitochondrial membrane potential in a C. elegans model of mitochondrial disease. Biochem 39 Conway GS. Premature ovarian failure. Brit Med Bull. 40 Goswami D, Conway GS. Premature ovarian failure. Hum Reprod Update. 2005; 11(4 41 Hu XM, Roberts JR, Apopa PL, Kan YW, Ma Q. diepoxide in Nrf2 null mice. Mol Cell Biol. 2006; 26(3): 更多精品文档,欢迎来我主页查询 42 Graziewicz MA, Bienstock RJ, Copeland WC. The DNA polymerase γ Y955C disease variant associated with PEO and parkinsonism mediates the incorporation and translesion ’ 43 Chen LL, Wu C, Li W. Study on antioxidative activity of flavonoids from Semen Cuscutae. Shi Pin Gong Ye Ke Ji. English. 陈林林, 吴春, 李伟. 菟丝子黄酮的抗氧化性能研究. 食品工业科 技 44 An HM, Shi YF, Hu B, Shi XF, Zhang ZP, Xu LW, Gu MC. Prepared Radix Rehmanniae (熟地黄) delay brain senescence English. 安红梅, 史云峰, 胡兵, 史秀峰, 张占鹏, 许丽雯, 顾明昌. 熟地 更多精品文档,欢迎来我主页查询 黄对半乳糖衰老模型大鼠脑衰老的作用研究. 中药药理与临床. 0. 45 Wu HH, Xuan GD, Liu CQ, Hu QH. Study on purification and antioxidant activity of phenylethanoid glycosides from Cistanche salsa. Shi Pin Ke Xue. 2008; 29(6): 吴海虹, 玄国东, 刘春泉, 胡秋辉. 肉苁蓉苯乙醇苷的纯化及其抗 氧化活性研究. 食品科学 46 Li Y, Su QQ. Study on antioxidant and antimicrobial activity of Morinda officinalis How water extract. Shi Pin Yu Ji 李妍, 苏倩清. 巴戟天水提取物油脂抗氧化性和抗菌活性研究. 食 品与机械. 2008; 2 47 Liu W, Liu CH, Yu HQ. Effect of Chuanxiong and Danggui on Na+ and K+ currents of rat hippocampal neurons 更多精品文档,欢迎来我主页查询 刘卫, 刘传缋, 俞惠琴. 中药川芎、当归有效成分对缺氧后复氧大 鼠海马神经元钠、钾电流的作用. 中国临床康复. 2006; 10(7): 48 Huang F, Xu LJ, Du GH, Xiao PG. In vitro antioxidative and cytotoxic activities of Schisandra sphenanthera Rehd. et Wils. Tian Ran Chan Wu Yan Jiu Yu Kai Fa. 2006; 18(1): th abstract in Chinese. 黄锋, 许利嘉, 杜冠华, 肖培根. 华中五味子抗氧化和细胞毒活性 研究. 天然产物研究与开发 women with premature ovarian failure who are resistant to hormone replacement therapy. Fertil Steril. 2003; 79(2): 上一页 1 2下一页 更多精品文档,欢迎来我主页查询