厄贝沙坦对高糖刺激的大鼠肾小球系膜细胞结缔组织生长因子及膜型基质金属蛋白酶-1表达的影响

Effects of irbesartan on the expression of CTGF and MT1-MMP in high glucose-induced rat glomerular mesangial cells

目的研究血管紧张素Ⅱ受体1拮抗剂厄贝沙坦对高糖刺激的大鼠肾小球系膜细胞结缔组织生长因子(CTGF)和膜型基质金属蛋白酶-1(MT1-MMP)表达的影响。方法体外培养的大鼠肾小球系膜细胞,分别给予高糖和厄贝沙坦干预,采用RT-PCR及Western blot法分别检测CTGF和MT1-MMP的mRNA及蛋白的表达,用酶联免疫吸附法(ELISA)检测培养上清中Ⅳ型胶原的含量。结果与对照组相比,高糖组各时间点系膜细胞CTGF表达明显上调,Ⅳ型胶原的分泌增加,且二者随时间持续增高;而MT1-MMP的表达则随时间呈明显下降趋势。厄贝沙坦能够抑制高糖引起的上述变化。结论高糖可诱导肾小球系膜细胞CTGF表达增加,抑制MT1-MMP的表达。厄贝沙坦抑制肾小球系膜细胞基质分泌的作用可能部分通过抑制CTGF,增加MT1-MMP的表达而实现。

Aim To investigate the effects of Ang Ⅱ receptor antagonist irbesartan on the expressions of connective tissue growth factor （CTGF） and membrane-type 1 matrix metalloproteinase （MTI-MMP） in high glucose-cultured rat glomerular mesangial cells （GMCs）. Methods High concentration glucose and irbesartan were used to stimulate the cultured rat GMCs in vitro. The mRNA and protein expressions of CTGF and MT1-MMP were detected with semi-quantitative RT-PCR and Western blot. The secreted collagen IV in the supernatants of the GMCs was detected by enzymelinked immunoadsorbent assay （ELISA）. Results Compared with control group, the expressions of CTGF were continuously increased in GMCs under high concentration glucose medium; otherwise the mRNA and protein levels of MT1-MMP in GMCs were decreased in a time-dependent manner at the same time. These changes were accompanied by increased secretion of collagen Ⅳ. Irbesartan could inhibit those changes induced by high glucose. Conclusions High glucose could induce the expression of CTGF and inhibit the expression of MT1-MMP in GMCs. Irbesartan could inhibit the secretion of ECM in GMCs under high concentration glucose medium,partly by regulating the ex-pressions of CTGF and MT1-MMP.