山萘酚通过增强Treg细胞免疫抑制功能延长移植物生存时间

目的:探讨应用山萘酚增强Treg细胞免疫抑制功能,从而抑制大鼠移植物排斥反应并改善移植物生存的作用和机制。方法:以Wister大鼠和SD大鼠分别为供、受体,建立同种异体皮肤移植排斥反应动物模型。观察受体老鼠皮肤移植物的情况,记录移植物失功时间(移植物皮片80%面积发生排斥)。RT-PCR检测移植7天后脾细胞、淋巴细胞FOXP3、CTLA-4和IL-10的mRNA水平,用HE染色组织病理学观察术后7天移植皮片的淋巴细胞浸润程度。体外实验T细胞增殖抑制试验加入山萘酚作为对照,观察Treg功能情况。结果:1.山萘酚能增强移植后同种异体移植物的生存时间(DMSO组6.3±0.3天,山萘酚组13.7±0.39天,P<0.01);2.RT-PCR显示山萘酚可增强细胞CTLA-4(对照组9.24±0.17,山萘酚组12.48±0.145,P<0.05)、FOXP3(对照组0.96±0.07,山萘酚组1.41±0.07,P<0.01)和IL-10(对照组0.95±0.12,山萘酚组1.50±0.16,P<0.05)的mRNA水平;3.体外T细胞增殖抑制实验中,山萘酚可增强Treg细胞的免疫抑制功能。结论:在大鼠皮肤移植模型中,山萘酚可延长皮肤移植物的生存时间,提高Treg细胞相关IL-10、FOXP3和CTLA-4的mRNA水平;体外实验中,能抑制效应T细胞的增殖,表明山萘酚在提高移植物生存方面存在一定的价值。

Kaempferol Prolongs the Graft Survival Time by Enhancing the Immunosuppressive Function of Treg Cells

ABSTRACT Objective: To explore the effect and mechanism of kaempferol on enhancing the immunosuppressive function of Treg cells, thereby inhibiting graft rejection and improving graft survival in rats. Methods: Wister rats and SD rats were used as donors and recipients to establish an allogeneic skin transplantation rejection animal model. The skin graft of recipient rats were observed, and the graft failure time was recorded(80% graft rejection). The mRNA levels of splenocytes and lymphocytes FOXP3, CTLA-4 and IL-10 were detected by RT-PCR 7 days after transplantation. The degree of lymphocyte infiltration of the transplanted skin grafts was observed by HE staining. In vitro T cell proliferation inhibition test, added kaempferol as a control group, observed the function of Treg cell. Results:1.Kaempferol can prolong the survival time of allografts after transplantation(DMSO group 6.3±0.3 days, kaempferol group 13.7±0.39 days, P<0.01). 2.RT-PCR shows that kaempferol can enhance the intracellular mRNA level of CTLA-4 (control group 9.24±0.17, kaempferol group 12.48±0.145, P<0.05), FOXP3(control group 0.96±0.07, kaempferol group 1.41±0.07, P<0.01) and IL-10(control group 0.95±0.12, kaempferol group 1.50) ±0.16, P<0.05). 3. In vitro T cell proliferation inhibition experiment, kaempferol can enhance the immunosuppressive function of Treg cells. Conclusion: In the rat skin graft model, kaempferol can prolong the survival time of skin grafts and increase the mRNA level of IL-10, FOXP3 and CTLA-4 in Treg cells. In vitro, it can inhibit the proliferation of effector T cells. The results indicated that kaempferol had certain value in improving the survival of grafts.