辛伐他汀对大鼠移植肝胆管损伤的防治作用-第三军医大学学报.DOC

辛伐他汀对大鼠移植肝胆管损伤的防治作用探索他汀类药物对大鼠胆管损伤的建立重建肝动脉的大鼠肝移植模型，设置实验组、对照组和假手术组，应用高效液相色谱法(HPLC)免疫组化PCR方法检测胆汁胆盐的成变化；观察肝脏组织的病理学变化；探讨辛伐他汀对大鼠移植肝磷脂变化的作用机制。明显增加大鼠胆汁中磷脂，组3.8748±1.4148）mg/dl与假手术组1.9821±0.4135）mg/dl和对照组1.4285±0.5387）mg/dl相比(P＜0.05)对照组肝脏组织胆管损毁严重而组的病理学变化则较对照组轻微磷脂转运蛋白(Mdr2 P-糖蛋白)Mdr2 mRNA的表达实验组较对照组有明显增强(P＜0.05)。辛伐他汀能增加大鼠移植术后胆汁中磷脂成的分泌移植肝胆管及肝脏组织。肝移植；胆道并发症；胆汁成分改变；辛伐他汀；磷脂；多药耐药-2Simvastatin prevents and treats ischemic-type biliary lesion in rats after liver transplantation Jiang Weiwei, Wang Shuguang, Chen Geng, Zhang Yujun (Institute of Hepatobiliary Surgery, Southwest Hospital, Third Military Medical University, Chongqing,400038,China） [Abstract] Objective To explore the preventive effects of statins on . Methods Totally 90 female SD rats, 6 to 8 weeks old, weighing 200 to 250 g, wre randomly divided into 3 groups, sham-operation group (n=10), control group (n=40, including 20 donors and 20 receipts), and experimental group (n=40, including 20 donors and 20 receipts). Rat liver transplantation was established by reconstructing hepatic artery. The rats of experimental group were fed with a normal chow containing 1% simvastatin for 1 week before operation and for 2 weeks after operation. The donor liver was stored in the University of Wisconsin solution at 4 ℃ for 12 h followed by transplantation. The animals were killed in 2 weeks after operation and the bile, bile duct and liver tissue were taken. High performance liquid chromatography (HPLC) was used to detect the concentrations of bile salts. Biochemistry, histopathology, immunohistochemistry and RT-PCR were employed to measure the level of Phospholipids C, observe the pathological changes of liver, detect the protein and mRNA expressions of phospholipid transfer protein (Mdr2 P-glycoprotein) for the mechanism of simvastatin on phospholipids changes in rat liver transplantation. Results The biliary phospholipid composition of rats in the experimental group (3.8748±1.4148 mg/dl) was significantly increased,compared with th