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目的探讨雷公藤内酯醇(triptolide,TPT)在小鼠同种异体胰岛移植中的抗排斥作用及其机理。方法采用BALB/c小鼠作为供体,进行胰岛分离,以链脲佐菌素(streptozotocin,STZ)诱导的C57BL/6糖尿病小鼠作为受体,行左肾被膜下胰岛移植。将移植后糖尿病小鼠随机(随机数字表法)分为3组,每组8只。于胰岛移植术后前5 d分别给予腹腔注射1%吐温80溶剂(对照组)、TPT 50μg/kg(L-TPT组)和100μg/kg(H-TPT组),之后隔天注射1次,至术后第14天结束。术后监测受体血糖水平变化;并于术后第10天每组随机(随机数字表法)选取3只小鼠,切取左侧肾脏行病理学检查,流式细胞术检测脾淋巴细胞中CD4+CD25+Foxp3+调节性T细胞比例。结果对照组、L-TPT组和H-TPT组移植胰岛的中位存活时间分别为12.6 d(9～16 d)、21.4 d(14～27 d)和27.6 d(19～34 d);脾淋巴细胞中CD4+CD25+Foxp3+调节性T细胞比例分别为(5.2±0.6)%、(12.0±1.3)%和(15.7±1.8)%。与对照组相比,L-TPT组和H-TPT组小鼠移植胰岛的中位存活时间明显延长(P<0.05),CD4+CD25+Foxp3+调节性T细胞比例显著增高(P<0.05)。结论 TPT通过上调移植受体CD4+CD25+Foxp3+调节性T细胞比例,减轻了胰岛移植后的排斥反应,显著延长了移植胰岛的存活时间,其免疫抑制作用呈剂量依赖性。
Objective To investigate the anti-rejection and its mechanism of triptolide (TPT) in allogeneic islet transplantation in mice. Methods BALB / c mice were used as donors for islet isolation. C57BL / 6 diabetic mice induced by streptozotocin (STZ) were used as recipients for subrenal islet transplantation. The diabetic mice after transplantation were randomized (random number table method) into three groups of eight. The mice were injected intraperitoneally with 1% Tween 80 (TPT 50μg / kg) and 100μg / kg (H-TPT) respectively in the first 5 days after islet transplantation. , To the end of the first 14 days after surgery. The blood glucose level of recipients was monitored after operation. Three mice were randomly selected from each group (random number table) on the 10th day after operation. The left kidney was excised for pathological examination and the percentage of CD4 + CD25 + Foxp3 + regulatory T cell ratio. Results The median survival time was 12.6 d (9-16 d), 21.4 d (14-27 d) and 27.6 d (19- 34 d) respectively in the control group, L-TPT group and H-TPT group. The percentage of CD4 + CD25 + Foxp3 + regulatory T cells in lymphocytes were (5.2 ± 0.6)%, (12.0 ± 1.3)% and (15.7 ± 1.8)%, respectively. Compared with the control group, the median survival time of transplanted islets in L-TPT group and H-TPT group was significantly prolonged (P <0.05), and the proportion of CD4 + CD25 + Foxp3 + regulatory T cells was significantly increased (P <0.05). Conclusion TPT can reduce the rejection after islet transplantation by increasing the proportion of CD4 + CD25 + Foxp3 + regulatory T cells in transplant recipients, and significantly prolong the survival time of transplanted islets. The immunosuppressive effect is dose-dependent.