雷公藤甲素PG490-88联合环孢素A免疫抑制诱导肾移植急性排斥反应模型大鼠的免疫耐受

Triptolide PG490-88 combined with ciclosporin A induces immune tolerance in a rat renal allograft rejection model

背景:近年来的研究发现雷公藤甲素具有很好的抗排异、抗肿瘤作用。PG490-88是雷公藤甲素的提取物,能够预防移植物抗宿主病和诱导免疫耐受。目的:探讨雷公藤甲素PG490-88联合环孢素A在大鼠肾移植急性排斥反应中诱导免疫耐受的作用。方法:改良法建立大鼠肾移植动物模型。40只Wistar大鼠做供体、40只SD大鼠做受体,随机数字表法均分为4组:对照组给予常规饮食。雷公藤甲素组给予雷公藤甲素PG490-8820mg/(kg·d)灌胃。环孢素A组给予环孢素A15mg/(kg·d)灌胃;联合治疗组:PG490-8820mg/(kg·d)+环孢素A15mg/(kg·d)灌胃。分别检测肾移植后各组1,3,5,7,14d外周血白细胞介素2受体水平和肾移植后大鼠的脾脏淋巴细胞组织中的白细胞介素2活性蛋白表达。结果与结论:3个治疗组的白细胞介素2活性和白细胞介素2受体均明显低于对照组(P<0.05)。其中,联合治疗组低于雷公藤甲素组和环孢素A组,差异有显著性意义(P<0.05)。提示,雷公藤甲素PG490-88通过对白细胞介素2、白细胞介素2受体的影响,来达到免疫抑制作用,不但具有免疫抑制作用,而且还能够诱导一定程度的免疫耐受,联合环孢素A效果会更好。

BACKGROUND：Studies demonstrated that triptolide has good effect on anti-rejection and anti-tumor. PG490-88 is extracted from triptolide,which can prevent graft versus host disease and induce immune tolerance. OBJECTIVE：To investigate the effect of PG490-88 combined with ciclosporin A on inducing immune tolerance in a rat renal allograft rejection model. METHODS：Kidney transplantation models were constructed using improved method. Forty Wistar rats served as donors,and 40 SD rats served as recipients. All rats were randomly divided into 4 groups. Rats were regular raised in the control group. Rats were lavaged with triptolide PG490-88 [20 mg/（kg·d）],ciclosporin A [15 mg/（kg·d）] or PG490-88 [20 mg/（kg·d）]＋ ciclosporin A [15 mg/（kg·d）] in the PG490-88,ciclosporin A or the combination group. Serum levels of interleukin 2-receptor （IL-2R） and activity of IL-2 in spleen lymph cells were detected respectively at 1,3,5,7 and 14 days after transplantation. RESULTS AND CONCLUSION：Serum levels of IL-2R and activity of IL-2 were detected lower in 3 treated groups than those in the control group （P 0.05）. Among the 3 treated groups,the combination group was lower than that of the PG490-88 and ciclosporin A groups （P 0.05）. Triptolide PG490-88 performs its function of immunosuppressant on the liver transplantation through IL-2 and IL-2R. It is not only has immunosuppressive action,but also can induce immune tolerance,the effects would be better when combined with ciclosporin A.