经胆道灌注化疗方案建立可行性的实验研究

目的 探讨经胆道灌注化疗对正常个体的肝脏、胆管上皮及胰腺的损伤和耐受情况,验证经胆道灌注化疗方案建立可行性.方法 选择正常SD大鼠为实验对象,采用开腹胆管插管方法灌注化疗药物,观察灌注后即刻肝细胞和胆管上皮的超微结构变化以明确损伤的机制并在不同时间段之后观察动物肝功能、血胰淀粉酶及胆管上皮、胰腺形态学变化.结果 胆管化疗药物灌注可造成谷草、谷丙转氨酶和总胆红素明显升高(P<0.05);胆管上皮微绒毛锐减乃至消失,肝细胞炎性改变、胆管上皮细胞的凋亡;虽然出现了短时间的胰腺组织中炎性细胞浸润的形态学变化,但血胰淀粉酶前后在统计学上无显著意义(P>0.05);随着时间的延长,这些损伤可以得到部分的修复,一些可以回到正常状态.结论 经胆管灌注并保留化疗药物会造成个体肝脏和胆管上皮的损伤,其机制为肝细胞和胆管上皮细胞亚细胞器出现破坏和凋亡.这种损伤在短期内就能可逆性的修复,动物是能够耐受的.

Experimental research on the feasibility of transbiliary chemotherapeutic infusion in normal rats

Objective To appraise the situation of damage and tolerance of liver,epithelium of bile duct and pancreas after transbiliary chemotherapeutic infusion in normal rats,to verificate the feasibility of establishment of a new adjuvant chemotherapy.Methods Normal SD rats were undergone with transbiliary infusion by explorative tansbiliary intubation,the chemotherapeutics sustained in bile duct for 30 minutes,then,transmission electron microscope was used to observe the ultrastructure of hepatocytes and biliary epithelial cells,whereas,changes of liver function,hemodiastase,biliary epithelial cells and pancreatic pathologic appearance were observed after different duration.Results Transbiliary chemotherpeutic infusion resulted in hepatocytes necrosis immediately,including severe increase of GPT,GOT.Microscopy showed microvilli of bile duct epithelial cells shortened or even disappeared,hepatocytes appeared inflammatory changes,some apoptosis of bile duct epithelial cells were also observed.The hemodiastase rised after chemotherapeutic infusion but had no statistical significance.Conclusion Transbiliary chemotherpeutic infusion will induce trauma in hepatocytes,bile duct epithelium and pancreas,but these trauma can be recovered in two weeks,the rats can be tolerant.