青藤碱对大鼠肾移植排斥反应时细胞间黏附分子-1表达的抑制作用

Immunosuppressive effect of Sinomenine on ICAM-1 expression in rat renal allograft rejection

目的 研究青藤碱 (SIN)的免疫抑制作用及其与环孢菌素A(CsA)的协同效应 ,并探讨SIN免疫抑制作用的机制。方法 建立 48个大鼠同种原位肾移植急性排斥反应模型(WistarSD) ,将其分为对照组、SIN组、CsA组、S +C组 ,每组 12例 ,每组随机抽取 6例观察大鼠移植肾受者存活时间 ,另 6例于术后第 6天处死 ,取移植肾组织标本行病理观察及免疫组织化学方法检测ICAM - 1表达并进行量化统计。分析SIN协同CsA对大鼠肾移植受者存活时间及对急性排斥反应时的肾组织细胞间黏附分子 - 1(ICAM - 1)表达水平的影响。结果 对照组受体大鼠均在术后 9d内死亡 ,生存 ( 7.83± 0 .75 )d ,SIN组为 ( 9.67± 0 .5 2 )d ,S +C组为( 2 5 .0 0± 4.65 )d ;移植肾组织ICAM - 1表达平均阳性面积单位在对照组为 ( 3 7.63±4.47) % ,SIN组为 ( 2 3 .48± 2 .88) %(P <0 .0 1) ,CsA组为 ( 2 5 .5 9± 2 .44 ) % (P <0 .0 1) ,S +C组为 ( 3 8± 2 .3 5 ) % (P <0 .0 5 )。结论 SIN可能通过下调ICAM - 1表达的机制对大鼠肾移植的急性排斥反应起到一定的抑制作用 ,并与CsA产生显著的协同作用 ,可减少CsA的用量 。

Objective It is to study the immunosuppressive efficacy of Sinomenine (SIN) and its synergetic effect with Cyclosporin A (CsA) and explore its immunosuppressive mechanism. Methods Allograft acute rejection model were established in 48 SD rats. They were divided into control group, SIN group, CsA group, S+C group at random. Allograft of six recipients from each group sacrificed at sixth day after operation and the transplanted allograft were studied with histological observation and histochemistry determination of ICAM-1 expression, while survival time of other six recipients in each group were recorded. The synergistic effects of SIN combined with CsA on survival time of recipients and expression of ICAM-1 during acute rejection were analyzed. Results All recipients in control group died within nine days after operation. Their mean survival time was (7.83±0.75) days. That of SIN group and S+C group respectively were (9.67±0.52) days and (25.00±4.65) days. Mean positive proportion unite of ICAM-1 expression in control group was(37.63±4.47)%, that of SIN group, CsA group and S+C group respectively were(23.48±2.88)%(P<0.05), (25.59±2.44)%(P<0.01), (38±2.35)%(P<0.05). Conclusion SIN has inhibitive effects on acute rejection of kidney allograft and combination of that with CsA has synergistic effects. The immunosuppressive mechanism of SIN probably induced by decreasing ICAM-1 expression. SIN can reduce the CsA dosage and then relieve the side effect of CsA on transplanted kidney.