大黄素对大鼠原位肝移植术后急性排斥反应的干预

Immunosuppressive effect of emodin on acute rejection after orthotopic liver transplantation in rats

目的:目前国外已有少量报道证实中药大黄素具有极强的免疫抑制效应。实验拟进一步验证大黄素对同种异体大鼠肝移植术后早期急性排斥反应的干预效果。方法:实验于2004-01/2005-02在西安交通大学第一附属医院肝胆外科实验室完成。制备SD→Wistar大鼠全血供肝移植模型(n=80),按随机数字表法分为4组,每组20只。模型对照组、大黄素组、环孢素A组及环孢素A+大黄素组分别腹腔注射给予9g/L生理盐水、1.5mg/(kg·d)大黄素、3mg/(kg·d)环孢素A及3mg/(kg·d)环孢素+1.5mg/(kg·d)大黄素。术后观察大鼠一般情况,并于第7天各组分别处死10只大鼠,取肝脏标本及血清,观察移植肝组织排斥反应强度、Fractalkine(Fkn)阳性表达情况及大鼠血清中白蛋白含量及谷丙转氨酶活性,余受体继续应用药物干预直至死亡,记录其生存时间。结果:各组受体手术成功数量分别为模型对照组17只、大黄素组18只、环孢素A组18只、环孢素A+大黄素组18只。①与模型对照组相比,各用药组大鼠术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。②与模型对照组相比,各用药组大鼠术后第7天移植肝排斥反应强度明显降低(P<0.05),血清中白蛋白含量明显升高,而谷丙转氨酶活性明显降低(P均<0.05),肝组织中Fkn表达阳性率明显降低(P<0.05),以环孢素A+大黄素组表现最为显著。结论:大黄素具有抑制同种异体大鼠肝移植急性排斥反应发生、发展的作用,与环孢素A联用具有协同作用。

AIM： A few reports have shown that emodin has immunosuppressive effect. This study was aimed to verify the effect of emodin on acute rejection in the early stage after hepatic allograft operation. METHODS：The experiment was performed at the Laboratory of Hepatobiliary Surgery, First Affiliated Hospital, Xi＇an Jiaotong University from January 2004 to February 2005. SD→Wistar rats were selected to establish orthotopic liver transplantation models （n =80）. These rats were randomized into 4 groups with 20 in each group. Rats in the model control group, emodin group, ciclospodn A group and ciclosporin A plus emodin group were intrapedtoneally treated with 9 g/L saline, 1.5 mg/kg per day emodin, 3 mg/kg per day ciclosporin A and 3 mg/kg ciclosporin A plus 1.5 mg/kg emodin per day respectively. General conditions of rats were observed after operation. Ten rats in each group were killed 7 days after transplantation. Hepatic samples and serum were collected to observe the intensity of acute rejection in liver tissue, expression of Fractalkine（Fkn）, levels of albumin （ALB） and alanine aminotransferase （ALT） in serum. The rest rats in each group were fed and continued to give different drugs or vehicle buffer until they were died and the mean of survival time were recorded. RESULTS： Seventeen rats in the model control group, 18 in the emodin group, 18 in the ciclosporin A group and 18 in the ciclosporin A plus emodin group. ①Compared with the model control group, the mean survival time was significantly longer in other groups （P 〈 0.05）, and the mean survival time was the longest in the ciclosporin A plus emodin group. Compared with the model control group, on the 7^th day after transplantation, the severity of acute rejection was remarkably lower in the other groups （P 〈 0.05）, but ALB level was obviously increased and ALT level was markedly decreased （P 〈 0.05）. The expression of Fkn in liver tissue was significantly decreased （P 〈 0.05）, especially in the ciclosporin A plus emodin group. CONCLUSION：Emodin can inhibit the severity of rat hepatic allograft acute rejection, and has synergistic effect with ciclospodn A.