小鼠皮肤移植中雷公藤内酯醇的免疫抑制作用及机制研究

Immunosuppressive effect and mechanism of Triptolide on skin allografts in mice

目的探讨雷公藤内酯醇(Triptolide,Tri)在小鼠同种异体皮肤移植中的免疫抑制作用及其可能的作用机制。方法采用BALB/c小鼠作为供体,C57BL/6小鼠作为受体,建立皮肤移植模型。随机分为3组,每组8只。移植术后前6天(0～5 d)分别予腹腔注射1%吐温80溶剂(对照组)、Tri 100μg/kg(L-Tri组)和Tri 200μg/kg(H-Tri组)。术后观察移植皮片存活情况。并于术后第7天每组随机选取3只,切取脾脏以流式细胞术检测脾淋巴细胞中CD4+CD25+Foxp3+T细胞比例。结果对照组、L-Tri组和H-Tri组移植皮片平均存活时间分别为(8.3±1.2)、(12.4±1.9)、(14.9±2.2)d;脾淋巴细胞中CD4+CD25+Foxp3+调节性T细胞比例分别为(5.6±0.8)%、(12.6±1.5)%和(16.1±2.1)%;L-Tri组及H-Tri组与对照组比较,H-Tri组与L-Tri组比较,小鼠移植皮肤平均存活时间均明显延长(P<0.05),CD4+CD25+Foxp3+T细胞数量也明显增加(P<0.05)。结论 Tri能够抑制移植后排斥反应,延长小鼠同种异体皮肤移植的存活时间,其免疫作用机制可能与上调移植受体CD4+CD25+Foxp3+T细胞的比例有关,并且其免疫抑制作用具有一定的剂量依赖性。

Objective To investigate the immunosuppressive effect and the possible mechanism of Triptolide on skin al-lografts in murine model. Methods BALB/c mice to C57BL/6 mice skin allografting models were created. The recipi-ents were divided into three groups. The mice in the treatment groups were injected intraperitoneally with Triptolide at 100μg/kg （low-dose Triptolide group, L-Tri group） or 200 μg/kg （high-dose Triptolide group, H-Tri group） daily in the first 6 days （0-5 days）;while the mice in control group were given vehicles （1% Tween 80）. The median survival time of skin allografts in each group was monitored. The proportion of CD4＋CD25＋Foxp3＋regulatory T cells in spleen tissue were tested by flow cytometry. Results The median survival time of skin allografts in the control group, L-Tri group and H-Tri group were （8.3±1.2）, （12.4±1.9） d and （14.9±2.2） d respectively. The percentage of CD4＋CD25＋Foxp3＋regulatory T cells in spleen tissues of three groups were （5.6±0.8）%, （12.6±1.5）%and （16.1±2.1）%respectively. Compared with control group, the L-Tri group and H-Tri group show significantly prolonged skin allograft survival time （P〈 0.05）, increased percentage of CD4＋CD25＋Foxp3＋regulatory T cells （P〈 0.05）. Conclusion Tri can inhibit im-mune rejection, prolong the skin allograft survival time in mice. The anti-rejection effect of Tri may be attributed to the upregulation of regulatory T cells. In addition, the immunosuppressive effect of triptolide shows dose-dependent.