HTK液逆行灌注可减轻肝脏隔离化疗对大鼠的损伤

目的:建立大鼠肝脏隔离灌注化疗模型;探讨在大剂量化疗药物肝脏隔离灌注过程中,HTK液经肝静脉逆行灌注对肝脏的保护及减少全身泄漏作用。方法:将75只体重300～350g的雄性SD大鼠随机分为3组,每组25只;手术建立大鼠隔离灌注化疗模型。A组经肝动脉灌注含30mg/L三氧化二砷的林格液,门静脉灌注林格液,肝静脉为流出道。B组经肝静脉灌注林格液,门静脉为流出道,余同A组。C组经肝静脉灌注4℃组氨酸-色氨酸-酮戊二酸(Histidine-Tryptophan-Ketoglutarat,HTK)液,余同B组。各组于术后1、2、3、7d各随机处死大鼠5只,进行血清肝功能及肝组织病理学检查。A组和B组大鼠术中检测体循环和肝循环中的血药浓度。结果:各组动物血清ALT和AST峰值均出现在术后第1天,其后开始下降,至术后7d恢复正常。术后第1、2、3d,3组间的血清ALT、AST均数均有显著性差异(P0.05);光镜下观察肝组织,进一步证实了上述结果。A组与B组间体循环血药浓度差异有统计学意义(P0.05),而两组间的肝循环血药浓度相类似;表明逆行隔离灌注的体循环泄漏率较顺行隔离灌注组为低。结论:低温HTK液逆行灌注可显著减轻肝脏隔离化疗对大鼠的损伤,提高手术的安全性。

Retrograde perfusion with HTK solution to diminish the degree of rat liver injury during isolated hepatic chemotheapy

Objective To investigate the protective effect and drug leakage by retrograde perfusion with HTK solution in the rat isolated hepatic perfusion model. Methods A total of 75 male Sprague-Dawley rats weighing between 300 and 350 g served to build the isolated hepatic perfusion model. and were randomly divided into 3 groups, each group had 25 rats. Group A： the hepatic artery was perfused with arsenite at a dose of 30 mg/L, the portal vein was perfused with Ringer′s Lactate, and the hepatic vein served as the outflow path. Group B： the hepatic vein was perfused with Ringer′s Lactate, and the portal vein served as the outflow path, the rest was similar to group A. Group C： the hepatic vein was perfused with 4 ℃ HTK solution, the rest was similar to group B. Five rats of each group were randomly killed on day1, day2, day3 and day7 after operation. Hepatic enzymes were examined and liver biopsies performed in all rats. The blood drug level of the systemic circulation and the liver circulation were measured in groups A and B during the operation. Results In all the groups, the levels of ALT and AST were highest on the first day, but declined to normal within 7 days. There were significant differences among groups A, B and C in hepatic enzymes （P0.05）, and hepatic tissue pathology confirmed the results. There existed significant differences between groups A and B in systemic circulation drug level （P 0.05）, while their drug level in the hepatic circulation was similar. Conclusions Retrograde perfusion with HTK solution could diminish the degree of liver injury during isolated hepatic perfusion.