舌动脉持续灌注论文：区域性动脉持续灌注5-FU局部组织及引流区淋巴结药物浓度的动态观察

舌动脉持续灌注论文：区域性动脉持续灌注5-FU局部组织及引流区淋巴结药物浓度的动态观察 舌动脉持续灌注论文:区域性动脉持续灌注5-FU局部组织及引流区淋巴结药物浓度的动态观察 【中文摘要】?建立颞浅动脉逆行插管、舌动脉持续灌注抗癌药物的犬动物模型。?比较经颞浅动脉逆行插管舌动脉灌注、外周股静脉输注5-FU,犬舌动脉供血区舌体、引流区域淋巴结组织内药物浓度差异及5-FU在犬体内的药物代谢动力学。?将16条健康家犬称重后随机分为A组(颞浅动脉逆行插管给药)和B组(股静脉给药)。分别经颞浅动脉、外周股静脉持续24小时灌注5-FU,给药剂量按体表面积计算。于不同时间点分别采集药物灌注血管对侧的颈静脉和股静脉血浆标本,进行药物浓度检测。A组分别在12h、24h用4条犬,采集置入泵侧舌体前2/3,舌体后1/3,下颌下淋巴结,置入泵对侧舌体前2/3,舌体后1/3,下颌下淋巴结组织。B组所用方法与A组相同,但舌体组织未分左右。?采用反相高效液相色谱法(RP-HPLC)检测以上采集的血浆及组织标本中5-FU含量。色谱条件为Agilent HC-C18色谱柱(150 mm×4.9 mm,5μm PN,588925-902);流动相:甲醇-水(95:5);流速1.OmL?min-1;柱温30?;检测波长265nm;进样量20.0μl。?用DAS2.0版药动学程序对血药浓度-时间数据进行拟合并计算药物代谢动力学参数;分别对血浆及组织中5-FU含量进行浓度差异比较。?正常犬在全麻状态下能经受24小时颞浅动脉逆行插管持续灌注5-FU并保持生命体征平稳。?5-FU在对侧颈静脉血浆中主要药动学参数为:A组(颞浅动脉逆行插管给药组)Tmax(14? 4.44)h,Cmax(565.35?82.62)mg?L-1;B组(股静脉给药组):Tmax(16?4.52)h,Cmax(457.29?59.74)mg?L-1;不同时间点A组血药浓度均大于B组血药浓度(P<0.05)。5-FU在对侧股静脉血浆中主要药动学参数为:A组(颞浅动脉逆行插管给药组)Tmax(16? 1.49)h,Cmax(391.52?67.14)mg?L-1;B组(股静脉给药组):Tmax(23?8.24)h,Cmax(526.36?77.44)mg?L-1;A组在给药后2小时内血药浓度高于B组,2小时后至结束,B组血药浓度均高于A组,二者相比均有明显差异(P<0.05)。?测得颞浅动脉逆行插管给药组持续灌注5-FU 24小时组织内药物浓度差异:同侧舌前2/3高于同侧舌后 Q/3(P=0.36),也高于对侧舌前2/3(P<0.01);同侧舌后1/3高于对侧舌后1/3(P=0.02);同侧下颌下淋巴结高于对侧下颌下淋巴结(P<0.01)。与股静脉给药组相比:颞浅动脉给药组同侧淋巴结药物浓度为股静脉给药组淋巴结的10-15倍(P<0.01),颞浅动脉给药组同侧舌前2/3、舌后1/3均高于股静脉给药组舌前2/3舌、舌后 1/3(P<0.01)。?杂交家犬是颞浅动脉逆行插管进行区域性动脉持续灌注抗癌药物(5-FU)的理想动物模型。?颞浅动脉逆行插管舌动脉持续灌注5-FU能使供血区舌组织内药物浓度明显高于股静脉给药。而股静脉给药进入全身循环的药量明显高于颞浅动脉给药。?颞浅动脉逆行插管持续舌动脉灌注置入泵侧舌体组织及引流区域淋巴结内5-FU药物浓度明显高于股静脉给药。 【英文摘要】[]?We investigated 5-FU concentration in tongue, the regional lymph nodes and pharmacokinetics with superficial temporal artery retrograde intubation for lingual artery continuous intraarterial and femoral vein infusion therapy in order to find a effective way for neoadjuvant chemotheapy for oral caner.[Methods]?Sixteen healthy dogs of the study, they were divided at random into two groups:A (superficial temporal artery retrograde intubation group) and B (femoral vein infusion group). Continuous infusion 5-FU through the superficial temporal artery or femoral vein for 24h. At different time points in A, B group contralateral jugular vein and femoral venous collected plasma samples. To take the dogs of the A group ipsilateral body of tongue, ipsilateral root of tongue, ipsilatera submandibular lymphatic nodes, contralateral boay of tongue,contralateral root of tongue, contralateral submandibular lymphatic nodes. To take the dogs of the B group body of tongue, root of tongue, submandibular lymphatic nodes in 12h and 24h.?The concentration of 5-FU in plasma and tissue at different times were determined by PR-HPLC. Analyses were carried out on an Agilent HC-C18C18(150 mm×4.9 mm,5μm PN,588925-902);column at 30?, eluted with a mobile phase consisting of methanol-water(95:5) and detected at 256 nm. The flow rate was 1.0 ml?min-1.?The concentration-time data were processed with DAS(2.0) pharmacokinetic procedure. Compare with 5-FU concentration levels of plasma and tissues.[Results]?The healthy dogs with anesthesia can withstand the superficial temporal artery retrograde 5-FU to continue 24h and to maintain stable vital signs.?Their pharmacokinetics parameters with collected plasma samples of contralateral jugular vein were as follows:A (superficial temporal artery retrograde intubation group) Tmax (14?4.44)h, Cmax (565.35?82.62) mg?L-1; B (femoral vein infusion group) Tmax (16?4.52)h, Cmax (457.29?59.74) mg?L-1; The plasma concentration of A group higher than the B group in different time points (P<0.05). Their pharmacokinetics parameters with collected plasma samples of contralateral femoral vein were as follows:A (superficial temporal artery retrograde intubation group) Tmax (16?1.49)h, Cmax (391.52?67.14) mg?L-1; B (femoral vein infusion group). Tmax (23?8.24)h, Cmax (526.36 ?77.44) mg?L-1; The plasma concentration of A group higher than the B group after jugular vein 5-FU 2h, The plasma concentration of the B group higher than the A group after 2h to the end (P< 0.05).?The differences in drug concentration of superficial temporal artery infusion group were as follows:ipsilateral body of tongue[(405.18?42.07)μg?g-1] higher than ipsilateral root of tongue[(290.82?73.79)μg?g-1] (P=0.36); ipsilateral body of tongue higher than contralateral body of tongue[(102.96?11.85)μg?g-1] (P<0.01); ipsilateral root of tongue higher than ipsilateral root of tongue[(85.06?23.08)μg?g-1] (P=0.02); ipsilatera submandibular lymphatic nodes[(254.00?31.04)μg?g-1] higher than contralateral submandibular lymphatic nodes[(70.09?2.36)μg?g-1] (P<0.01). Compared with the femoral vein administration:ipsilateral submandibular lymphatic nodes of the superficial temporal artery retrograde intubation group drug concentration for the femoral vein retrograde group[(0.56?0.98)μg?g-1] 10 to 15 times (P<0.01), ipsilateral body of tongue of the superficial temporal artery retrograde intubation group higher than the body of tongue [(29.31?1.43)μg?g-1] of the femoral vein infusion group(P<0.01), ipsilateral root of tongue [(5.59? 1.55)μg?g-1] of the superficial temporal artery retrograde intubation group higher than the root of tongue of the femoral vein infusion group (P<0.01)[Conclusion]?Dogs for the establishment of regional arterial retrograde continuous administration of animal models.?Through the superficial temporal artery retrograde intubation, head neck region 5-FU drug concentrations higher than femoral vein infusion; Through femoral vein infusion into the systemic circulation of the drug administration was significantly higher than of superficial temporal artery.?Ipsilateral tongue and ipsilatera submandibular lymphatic nodes of the superficial temporal artery retrograde intubation groups 5-FU drug concentrations higher than femoral vein infusion. 【关键词】舌动脉持续灌注 5-FU 引流区域淋巴结 舌体组织 药 物代谢动力学 【英文关键词】Lingual artery infusion 5-FU Draining regional lymph nodes Tongue tissue Pharmacokinetics 【备注】索购全文在线加好友:1.3.9.9.3.8848 同时提供论文写作一对一指导和论文发表委托服务 【目录】区域性动脉持续灌注5-FU局部组织及引流区淋巴结药 物浓度的动态观察 英文缩略词表 5-6 摘要 6-8 Abstract 8-10 前言 11-14 材料与方法 14-19 结果 19-31 讨论 31-34 结论 34 参 考文献 34-37 综述 37-46 参考文献 44-46 致谢 46-48 作者简介 48