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目的:观察血管紧张素受体拮抗剂(ARBs)L158,809和血管紧张素转换酶(ACE)抑制剂西拉普利对体外培养人肾小球系膜细胞转化生成因子(TGF-β_1)表达和纤维连接蛋白、层粘连蛋白和Ⅳ型胶原分泌的影响。方法:分别在不同葡萄糖浓度(5.6 mmol/L和30 mmol/L)和药物浓度(1、10、100和500 μ mol/L)下体外培养人肾小球系膜细胞,分别于24、48和72 h后测定细胞增殖。然后将系膜细胞分为低糖(5.6 mmol/L)对照组(LG)、高糖(30 mmol/L)对照组(HG)、L158,809(10 μmol/L)组和西拉普利(10 μmol/L)组,48 h后,分别用RT-PCR法测定TGF-β_1表达,ELISA和放射免疫法测定细胞上清液中TGF-β_1、纤维连接蛋白、层粘连蛋白和Ⅳ胶原浓度。结果:与低糖对照组相比,高糖对照组系膜细胞过度增殖,细胞上清液中TGF-β_1、纤维连接蛋白、层粘连蛋白和Ⅳ胶原浓度明显升高,TGF-β_1 mRNA表达也显著升高;而L158,809组和西拉普利组TGF-β_1和细胞外基质(ECM)蛋白水平明显低于高糖对照组,且TGF-β_1 mRNA水平亦表达明显降低。结论:高糖可刺激体外培养系膜细胞过度增殖,TGF-β_1表达增高,ECM蛋白分泌明显增加,而L158,809和西拉普利均可抑制高糖环境下上述现象。
OBJECTIVE: To observe the effects of angiotensin receptor blocker (ARBs) L158,809 and angiotensin converting enzyme (ACE) inhibitor cilazapril on the expression of transforming growth factor-β (TGF-β1) in cultured human glomerular mesangial cells And fibronectin, laminin and type Ⅳ collagen secretion. Methods: Human mesangial cells were cultured in vitro at different concentrations of glucose (5.6 mmol / L and 30 mmol / L) and drug concentrations (1, 10, 100 and 500 μmol / L) After 72 h, cell proliferation was measured. The mesangial cells were divided into low glucose (5.6 mmol / L) control group (LG), high glucose (30 mmol / L) control group (HG), L158,809 (10 μmol / L) group and cilazapril 10 μmol / L). After 48 h, the expression of TGF-β 1 was measured by RT-PCR. The concentrations of TGF-β 1, fibronectin, laminin and collagen Ⅳ in the supernatant were measured by ELISA and radioimmunoassay. RESULTS: Compared with the low glucose control group, the mesangial cells in hyperglycemic control group were hyperproliferative. The concentrations of TGF-β 1, fibronectin, laminin and Ⅳ collagen in the supernatant were significantly increased, and the expression of TGF-β 1 mRNA was also significantly increased While the protein levels of TGF-β 1 and extracellular matrix (ECM) in L158,809 and Cilazapril groups were significantly lower than those in high glucose control group, and the expression of TGF-β_1 mRNA was also significantly decreased. CONCLUSION: High glucose can stimulate the proliferation of mesangial cells in vitro, increase the expression of TGF-β 1 and increase the secretion of ECM protein, while L158,809 and Cilazapril can inhibit the above phenomena under high glucose.