骨髓间充质干细胞对IgA肾病大鼠TGF-β_1和MCP-1的影响

Effects of bone marrow mesenchymal stem cells on TGF-β_1 and MCP-1 in rats with IgA nephropathy

目的:观察骨髓间充质干细胞(BMSCs)移植对于IgA肾病大鼠肾脏中细胞因子TGF-β1和MCP-1的影响。方法:SD大鼠分为MSCs注射组、生理盐水组及正常对照组。前两组以牛血清白蛋白(BSA)+葡萄球菌肠毒素B(SEB)+皮下注射四氯化碳(CCL4)法建立IgA肾病模型。体外连续培养SD大鼠BMSCs。用ELISA法检测尿中的TGF-β1、MCP-1水平,用RT-PCR技术检测肾组织中二者的表达情况,并通过免疫组化法观察两种细胞因子在肾组织中的蛋白表达。结果:移植后1周,检测MSCs组大鼠尿上清细胞因子TGF-β1(5.38±0.99)ng/mL,MCP-1(287.67±17.41)pg/mL;NS组TGF-β1(7.84±0.98)ng/mL,MCP-1(359±10.49)pg/mL。两组相比P<0.05。移植后4周,MSCs组TGF-β1(2.78±0.35)ng/mL,MCP-1(197.83±15.16)pg/mL;NS组TGF-β1(9.18±0.64)ng/mL,MCP-1(403.5±19.27)pg/mL。两组相比,P<0.05。且两种细胞因子在两组大鼠肾免疫组化蛋白表达及肾组织中mRNA表达上比较均有统计学意义。结论:静脉输注BMSCs后肾脏内的TGF-β1、MCP-1明显减少,且有延续效应,可能是MSCs修复IgA肾病的重要机制之一。

Objective To research the effects of bone marrow mesenchymal stem cells （BMSCs） on the expressions of TGF-13~ and MCP-1 in the kidney of rats with IgA nephropathy. Methods Sprague-Dawley rats were randomly divided into 3 groups： BMSCs group were injected with BMSCs; NS group were injected with saline; normal control group were injected with nothing. IgA nephropathy model was estabhshed by the method of BSA＋ SEB＋CCL4 in BMSCs and NS groups. BMSCs of SD rats were continuous cultured in vitro routinely. At 1＊ and 4a week after BMSCs were injected, expressions of MCP-1 and TGF-β1 in urine were detected by ELISA. The expressions of MCP-1 and TGF-β1 mRNA and protein in kidney were examined by RT-PCR or immunohistochemistry, respectively. Results At the end of 1＊ week, the concentrations of MCP- 1 and TGF-β1 in urine in BMSCs group were （287.67± 17.41 ） pg/mL and （5.38 ± 0.99） ng/mL, respectively; and those in NS group were （359 ± 10.49） pg/mL and （7.84± 0.98） ng/mL, respectively （P 〈 0.05）. At the end of 4th week, the concentrations of TGF-β1 and MCP-1 in BMSCs group were （2.78 ± 0.35） ng/mL and （197.83 ± 15.16） pg/mL, respectively; and those in NS group were （9.18 ± 0.64） ng/mL and （403.5 ± 19.27） pg/mL, respectively （P 〈 0.05）. The differences of the expressions of MCP-1 and TGF-β1 mRNA and protein between BMSCs group and NS group were significant. Conclusions Intravenous infusion with BMSCs could markedly decrease the concentrations of TGF-β1 and MCP-1 in kidney and the effects could last as time increased; which may be one of the possible mechanisms of BMSCs repairing IgA nephropathy.