Key Laboratory of Preclinical Study for New Drugs of Gansu Province, Department of Pharmacology, School of Basic Medical Sciences, Lanzhou University, Lanzhou, Gansu, China.
J Surg Res. 2012 Jul;176(1):267-74. doi: 10.1016/j.jss.2011.06.038. Epub 2011 Jul 21.
Organ transplantation is a life-saving procedure for patients with organ failure. However, the side effects of long-term application of classic immunosuppressant remain major obstacles for successful transplantation. Therefore, new and safe immunosuppressive drugs against acute and chronic rejection are eagerly awaited.
In the present study, we detected the effect of ginsenoside-Rd on mitogen-induced mouse spleen lymphocytes proliferation in vitro and observed the effect of ginsenoside-Rd on allograft rejection in a rat skin transplantation model. Th1/Th2 type cytokines secretion and T-cell subsets were also detected.
The results showed that ginsenoside-Rd could markedly inhibit Concanavalin A (ConA)-induced mouse spleen T lymphocytes proliferation. Also, ginsenoside-Rd could significantly prolong the mean survival time of skin allograft and improve the skin allograft pathological damage. Furthermore, ginsenoside-Rd could markedly suppress alloantigen-specific production of Th1 cytokines IL-2 and IFN-γ as well as proinflammatory cytokines TNFα and IL-12. In parallel, Th2 cytokine IL-10 production in serum of rat recipients was markedly up-regulated. Ginsenoside-Rd at a dose of 25 mg/kg could significantly reduce the percentages of CD4(+) T cells and CD8(+) T cells in peripheral blood of rat recipients.
Our results suggest that ginsenoside-Rd can effectively antagonize transplant rejection, which might qualify ginsenoside-Rd as a putative, therapeutic drug for the treatment of Th1-driven diseases, including transplant rejection.
器官移植是治疗器官衰竭患者的一种救生程序。然而，长期应用经典免疫抑制剂的副作用仍然是成功移植的主要障碍。因此，新的和安全的免疫抑制剂，以对抗急性和慢性排斥反应，正急切期待。
在本研究中，我们检测了人参皂苷-Rd 对丝裂原诱导的小鼠脾淋巴细胞体外增殖的影响，并观察了人参皂苷-Rd 在大鼠皮肤移植模型中对同种异体移植排斥的影响。还检测了 Th1/Th2 型细胞因子的分泌和 T 细胞亚群。
结果表明，人参皂苷-Rd 能明显抑制刀豆蛋白 A（ConA）诱导的小鼠脾 T 淋巴细胞增殖。此外，人参皂苷-Rd 能显著延长皮肤同种异体移植物的平均存活时间，改善皮肤同种异体移植物的病理损伤。此外，人参皂苷-Rd 能显著抑制同种抗原特异性产生 Th1 细胞因子 IL-2 和 IFN-γ 以及促炎细胞因子 TNFα 和 IL-12。同时，大鼠受者血清中 Th2 细胞因子 IL-10 的产生明显上调。人参皂苷-Rd 剂量为 25mg/kg 时，能显著降低大鼠受者外周血中 CD4+T 细胞和 CD8+T 细胞的百分比。
我们的结果表明，人参皂苷-Rd 能有效拮抗移植排斥反应，这可能使人参皂苷-Rd 成为治疗 Th1 驱动疾病（包括移植排斥反应）的潜在治疗药物。
