L158,809和西拉普利对体外培养系膜细胞TGF-β1表达和细胞外基质蛋白分泌的影响

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—β1)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(5.6mmol／L和30mmol／L)和药物浓度(1、10、100和500μmol／L)下体外培养人肾小球系膜细胞，分别于24、48和72h后测定细胞增殖。然后将系膜细胞分为低糖(5．6mmol／L)对照组(LG)、高糖(30mmol／L)对照组(HG)、L158，809(10μmol／L)组和西拉普利(10μmmol／L)组，48h后，分别用RT-PCR法测定TGF-β1表达，ELISA和放射免疫法测定细胞上清液中TGF-β1、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-βl、纤维连接蛋白、层粘连蛋白和Ⅳ胶原浓度明显升高，TGF-βlmRNA表达也显升高；而L158，809组和西拉普利组TGF-β1和细胞外基质(ECM)蛋白水平明显低于高糖对照组，且TGF-β1mRNA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-β1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。

Effect of L158,809 and Cilazapril on the Expression of TGF-β1 and Secretion of Extracellular Matrix Proteins in Cultured Human Mesangial Cells

Objective: To explore the effect of L158,809 ( angiotensin Ⅱ receptor blockers, ARBs ) and Cilazapril ( Angiotensin converting enzyme inhibitor, ACEI ) on the expression of transforming growth factor-β1 ( TGF-β1 ) and secretion of fibronectin, laminin and type Ⅳ collagen from the cultured human mesangial cells. Methods: Human mesangial cells were cultured in different glucose (5.6 mmol/L and 30 mmol/L) and agents (1, 10, 100 and 500μmol/L) concentrations. The proliferation of mesangial cells were detected at 24, 48 and 72 h. Then the mesangial cells are divided into four groups, low glucose (5.6 mmol/L)control group, high glucose (30 mmol/L) control group, L158,809 (10 μmol/L) group and cilazapril (10μmol/ L) group. Forty-eight hours later, the expression of TGF-β1 were detected by RT-PCR. Concentrations of TGF-β1 , fibronection, laminin and type Ⅳ collagen in the supernatants of the mesangial cells were determined by ELISA and radioimmunoassay methods.Results: Compared with low glucose control group, the mesangial cells under high glucose medium show excessive proliferation and more TGF-β1 , fibronectin, laminin and type Ⅳ collagen in the supernatant. The expressicn of TGF-β1 mRNA was also significantly increased under high glucose. The levels of TGF-β1 and ECM ( extracellular matrix ) proteins in the L 158,809 group and cilazapril group are obviously lower than that of the high glucose control group. The expression of TGF-β1 mRNA was markedly decreasedin the L158, 809 group and cilazapril group compared with that of high glucose control group. Conclusion : High glucose stimulated the cultured human mesangial cells to excessively proliiferate, express TGF-β1 and secrete ECM proteins, and the high glucose-induced changes were suppressed by either L 158,809 and cilazapril.