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背景:抑制急性排斥反应的高效免疫抑制剂为器官移植所必需,较多的中药成分具有免疫调节作用。课题组在前期实验成功建立全血供大鼠肝移植模型基础上,初步发现大黄素对大鼠肝移植后急性排斥反应具有抑制作用,而且这种抑制作用可以通过多途径达到。目的:观察大黄素对同种异体大鼠肝移植后早期急性排斥反应过程中肝细胞凋亡的影响。设计、时间及地点:随机对照动物实验,于2005-04/09在西安交通大学第一附属医院肝胆外科实验室完成。材料:供体选用SD大鼠80只,雌雄不限;受体选用雄性Wistar大鼠80只,制备SD→Wistar大鼠全血供肝移植模型。方法:将制备的80只大鼠模型按随机数字表法分为4组,每组20只。于移植后第1天开始按分组设计行腹腔内药物注射,模型对照组仅给予生理盐水,大黄素组给予大黄素1.5mg/(kg·d),环孢素A组给予环孢素A3mg/(kg·d),环孢素A+大黄素组给予环孢素A3mg/(kg·d)+大黄素1.5mg/(kg·d)。主要观察指标:移植后第7天各组处死10只大鼠,取肝脏标本,观察移植肝组织急性排斥反应强度、肝细胞凋亡指数、Bcl-2蛋白的表达。余受体继续应用药物干预直至死亡,记录其生存时间。结果:与模型对照组相比,大黄素组、环孢素A组、环孢素A+大黄素组大鼠移植后存活时间明显延长(P<0.05),以环孢素A+大黄素组存活时间最长。移植后第7天,与模型对照组相比,大黄素组、环孢素A组、环孢素A+大黄素组大鼠移植肝排斥反应强度、肝细胞凋亡指数显著降低(P<0.05),Bcl-2蛋白表达水平显著升高(P<0.05);大黄素+环孢素A组大鼠的移植肝排斥反应强度、肝细胞凋亡指数显著低于其他3组(P<0.05),Bcl-2蛋白表达水平显著高于其他3组(P<0.05)。结论:大黄素具有抑制同种异体大鼠肝移植急性排斥过程中肝细胞凋亡程度,改善肝功能的作用,与环孢素A具有一定的协同作用,同时又能减轻环孢素A引起的肝功能损害。
BACKGROUND: Highly effective immunosuppressants that inhibit acute rejection are required for organ transplantation, and more Chinese herbal components have immunoregulatory effects. Based on the successful establishment of a model of whole blood donor rat liver transplantation, the research group initially found that emodin has an inhibitory effect on acute rejection after liver transplantation in rats, and this inhibition can be achieved through multiple approaches. OBJECTIVE: To observe the effect of emodin on hepatocyte apoptosis during acute rejection following liver transplantation in allogenic rats. DESIGN, TIME AND SETTING: A randomized controlled animal experiment was performed at the Department of Hepatobiliary Surgery, First Affiliated Hospital of Xi’an Jiaotong University from April 2005 to September 2009. MATERIALS: A total of 80 SD rats were selected for the donor, male or female; 80 male Wistar rats were used as recipients to prepare SD-Wistar rat models of donor liver transplantation. Methods: The prepared 80 rat models were divided into 4 groups according to the random number table method, 20 in each group. On the 1st day after transplantation, intraperitoneal injections were started according to the group design. The model control group was given only saline, the emodin group was given emodin 1.5 mg/(kg·d), and the cyclosporine group A was given cyclosporine A 3 mg/ (kg·d), cyclosporine A + emorin group was given cyclosporine A 3 mg/(kg·d) + emodin 1.5 mg/(kg·d). MAIN OUTCOME MEASURES: On the 7th day after transplantation, 10 rats were sacrificed in each group. Liver specimens were taken to observe the acute rejection reaction, liver cell apoptosis index, and Bcl-2 protein expression in the transplanted liver tissue. The remaining receptors continued to use drug intervention until death, and their survival time was recorded. Results: Compared with the model control group, the survival time of emodin group, cyclosporine A group, and cyclosporine A + emodin group rats was significantly prolonged (P<0.05), and the survival time of cyclosporine A + emodin group longest. On the 7th day after transplantation, compared with the model control group, liver transplantation rejection and hepatocyte apoptosis index were significantly decreased in emodin group, cyclosporine A group, and cyclosporine A+emodine group (P<0.05). The expression of Bcl-2 protein was significantly increased (P<0.05). The liver transplantation rejection and hepatocyte apoptosis were significantly lower in emodin + cyclosporine A rats than in the other three groups (P<0.05). The expression of Bcl-2 protein was significantly higher than that of the other three groups (P<0.05). Conclusion: Emodin can inhibit the degree of hepatocyte apoptosis and improve hepatic function during allograft rat acute rejection of liver transplantation. It has a certain synergistic effect with cyclosporine A and can reduce cyclosporine A induced Liver damage.