普伐他汀对高糖培养的肾小球系膜细胞增殖和细胞外基质积聚的影响

Effect of pravastatin on extracellular matrix synthesis and degradation in glomerular mesangial cells cultured in high concentration of glucose

目的:探讨普伐他汀对高糖培养的肾小球系膜细胞(MC)增殖和细胞外基质(ECM)积聚的影响。方法:大鼠MC分别培养在低糖组、高糖组及普伐他汀组。CCK-8测定MC增殖,ELISA法检测细胞培养上清液Ⅳ型胶原(Col-Ⅳ)、纤维连接蛋白(FN)、转化生长因子-β1(TGF-β1)、基质金属蛋白酶组织抑制因子-1(TIMP-1)的分泌情况,明胶酶谱法检测基质金属蛋白酶-2(MMP-2)和基质金属蛋白酶-9(MMP-9)的活性,RT-PCR法检测结缔组织生长因子(CTGF)mRNA的表达。结果:与低糖组相比,高糖能促进Col-Ⅳ、FN合成,抑制MMP-2、MMP-9活性,增加TIMP-1、TGF-β1、CTGF的分泌,而普伐他汀能一定程度上逆转上述现象。结论:普伐他汀能抑制高糖环境下的MC增殖,并通过抑制ECM的合成、促进ECM的降解减少ECM积聚,机制可能与抑制TGF-β1、CTGF有关。

Objective To investigate the effect of pravastatin on the proliferation of glomerular mesangial cells cultured in high concentration of glucose and accumulation of extracellular matrix （ECM）. Methods Rat mesangial cells were cultured with low or high concentration of glucose or with pravastatin. Cell proliferation was assessed by CCK- 8, synthesis of FN and Col-Ⅳ and secretion of TGF-β1 and TIMP-1 in the cultured cells were determined by ELISA, MMP-2 and MMP-9 activities were determined by gelatin zymography, and expression of CTGF mRNA was detected by RT-PCR. Results Glucose in high concentration stimulated the synthesis of FN and Col-Ⅳ and the secretion of TGF- β1, CTGF, and TIMP-1, while inhibited MMP-2 and MMP-9 activities. However, pravastatin suppressed these high glucose-induced changes. Conclusion Pravastatin inhibits the mesangial cell proliferation induced by high glucose and reduces deposition of ECM, which may be associated with inhibiting the expressions of TGF-β1 and CTGF.