雷公藤内酯醇在小鼠同种异体胰岛移植中的抗排斥作用

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。

Anti-Rejection Effect of Triptolide on Islet Allografts in Chemically Induced Diabetic Mice

Objective To investigate the anti-rejection effect and the mechanism of triptolide（TPT）on islet allografts in a murine model.Methods BALB/c mice were used as islet donor.C57BL/6 mice were rendered diabetic by streptozotocin（STZ）injection,and transplanted with islets under the left kidney capsule.The recipients were randomly（method of random digits table）divided into three groups（n=8）.The mice in the treatment groups were injected intraperitoneally with TPT at 50 μg/kg（low-dose TPT group,L-TPT group）or 100 μg/kg（high-dose TPT group,H-TPT group）daily in the first 5 days and then on alternate days until 14 days;while the mice in control group were given vehicles（1% tween 80）.Blood glucose after operation were monitored.The grafts were defined as rejection when two consecutive reading of blood glucose20 mmol/L.The left kidney of three recipients in each group were resected for pathological examination.The proportion of CD4 ＋ CD25 ＋ Foxp3 ＋ regulatory T cells in spleen tissues were tested by flow cytometry.Results The median survival time of islet allografts from the control group,L-TPT group,and H-TPT group were 12.6 days（9-16 days）,21.4 days（14-27 days）,and 27.6 days（19-34 days）,respectivly.The percentage of CD4 ＋ CD25 ＋ Foxp3 ＋ regulatory T cells in spleen tissues of three groups were（5.2±0.6）%,（12.0±1.3）%,and（15.7±1.8）%,respectivly.Compared with control group,the median survival time of islet transplantation in mice extended and the proportion of CD4 ＋ CD25 ＋ Foxp3 ＋ regulatory T cells in spleen tissues increased（P0.05）.Conclusions TPT could increase the percentage of CD4 ＋ CD25 ＋ Foxp3 ＋ regulatory T cells,reduce the rejection after islet transplantation,and prolong the survival time of islet transplantation in mice.The immunosuppressive effect of TPT shows a dosedependent.