姜黄素对骨髓间充质干细胞诱导肾移植免疫耐受的影响

Effects of curcumin on mesenchymalstem cells-induced immune tolerance to kidney transplantation

背景:已有研究显示在大鼠肾移植时连续给予1×107细胞浓度的骨髓间充质干细胞可诱导免疫耐受,但临床上尚未发现姜黄素对肾移植具有免疫调节作用。目的:在对肾移植后的大鼠给予骨髓间充质干细胞的基础上,同时给予不同剂量姜黄素,观察其免疫耐受的效果。方法:建立大鼠肾移植模型,随机分为4组:纯肾移植组,无治疗措施;骨髓间充质干细胞组:关腹前左骼静脉注射1×107/kg骨髓间充质干细胞,第2天起尾静脉注射等量细胞,共10 d;骨髓间充质干细胞+低/高剂量姜黄素组:除给予骨髓间充质干细胞外,分别以2,10 mg/kg姜黄素溶液灌胃,共10 d。免疫组织化学染色法检测各组肾组织中转化生长因子β1的蛋白表达水平,酶联免疫吸附法检测血清中白细胞介素2,6水平。结果与结论:大鼠经肾移植后,纯肾移植组中肾小管上皮细胞以及间质细胞的转化生长因子β1蛋白表达、白细胞介素2,6水平均高于其他各组(P<0.05)。与骨髓间充质干细胞组比较,骨髓间充质干细胞+低/高剂量姜黄素组的转化生长因子β1的蛋白表达降低(P<0.05),血清白细胞介素2,6水平均低于骨髓间充质干细胞组(P<0.05)。结果证实,大鼠肾移植时同时给予姜黄素与骨髓间充质干细胞注射,可有效地进行免疫调节,抑制性免疫排斥反应的发生,保护肾功能。

BACKGROUND：Previous studies have shown that continuous administration of 1x107 of bone marrow mesenchymal stem cel s can induce immune tolerance in rats undergoing kidney transplantation, but it is not yet found clinical y that curcumin exerts an on immunomodulatory effect on kidney transplantation. OBJECTIVE：To investigate the effects of different concentrations of curcumin on bone marrow mesenchymal stem cel s-induced immune tolerance in rats after kidney transplantation. METHODS：Rat model of kidney transplantation was made, and rat models were randomly divided into four groups：transplantation group with no treatment;bone marrow mesenchymal stem cel s group （cel group） injected with 1＆#215;107/kg bone marrow mesenchymal stem cel s via the left iliac vein （before peritoneal suture） and tail vein （from the 2nd day） for 10 days;bone marrow mesenchymal stem cel s＋low/high dosage of curcumin groups （low/high dosage curcumin groups） injected intragastrical y with 2 or 10 mg/kg curcumin combined with injection of bone marrow mesenchymal stem cel s for 10 days. Transforming growth factor-β1 protein expression in the kidney tissues was examined by immunohistochemical staining. The concentrations of interleukin-2 and interleukin-6 in serum were detected by ELISA assay. RESULTS AND CONCLUSION：After kidney transplantation, the protein expression of transforming growth factor-β1 in renal tubular epithelial cel s and renal interstitial cel s as wel as the concentrations of interleukin-2and interleukin-6 in serum were significantly higher in the transplantation group than the other groups （P〈0.05）. Compared with the cel transplantation group, the protein expression of transforming growth factor-β1 as wel as the concentrations of interleukin-2 and interleukin-6 reduced significantly in the low/high dosage curcumin groups （P〈0.05）. These findings indicate that simultaneous administration of curcumin and bone marrow mesenchymal stem cel s can effectively inhibit immune rejection reaction and improve renal function in rats after kidney transplantation.