依那普利对高糖诱导的大鼠肾小球系膜细胞增殖及分泌TGF-1β、LN的影响

目的 观察依那普利（Ena）对高糖诱导的大鼠肾小球系膜细胞（GMCs）增殖及分泌转化生长因子-β1（TGF-β1）和层粘连蛋白（LN）的影响.方法 大鼠GMCs分别培养于正常浓度葡萄糖（NG,5.5mmol/L）、高浓度葡萄糖（HG,20mmol/L）及高糖和不同浓度（10-7mol/L、10-6mol/L、10-5mol/L）的Ena中,同时设空白对照.分别采用四甲基偶氮唑蓝（MTT）法和酶联免疫吸附试验（ELISA）、放射免疫法（RIA）检测不同时间（24 h、48 h、72 h）GMCs增殖情况和细胞培养上清液中TGF-β1、LN的含量.结果 与空白对照组比较,正常糖组和高糖组GMCs增殖增加,TGF-β1、LN分泌增多（P〈0.001）,高糖组更明显（P〈0.001）.与高糖组比较,高、中、低浓度的Ena干预均可逆转上述变化.且在一定浓度范围内,Ena无明显细胞毒性.结论 高糖可致GMCs增殖和TGF-β1、LN分泌增多,Ena可抑制高糖诱导的GMCs增殖与分泌TGF-β1、LN,这可能是其减少细胞外基质（ECM）积聚的机理之一,并有利于延缓糖尿病肾病肾小球硬化（GS）的进展.

Effect of Enalapril on Proliferation of Rat Glomerular Mesangial Cells and Transforming Growth Factor-β1,Laminin Secretion Induced by High Glucose

Objective To investigate the effect of enalapril （Ena） on proliferation of rat glomerular mesangial cells（GMCs） and transforming growth factor-β1 （TGF-β1）, laminin （LN） secretion induced by high glucose. Methods GMCs are cultured in normal concentration glucose （ NG）, high concentration glucose（HG） and HG plus different concentrations of enalapril for different duration（24 h ,48 h ,72 h）. Simultaneously, blank control is set up. Proliferation of GMCs is assessed by MTT assay. The contents of TGF-β1 , LN in the supernatant of cultured GMCs are detected by ELISA and RIA, respectively. Results Compared with blank control group, proliferation of GMCs increases in NG and HG groups（ P 〈 0. 001 ）. The secretion of TGF-β1 , LN are higher in NG and HG groups （ P 〈 0. 001 ）, with HG group more significant（ P 〈 0. 001 ）. Compared with HG group, HG plus high, middle,low concentrations of enalapril can reverse the changes, with no cell toxicity in a certain concentration range. Conclusion High glucose can induce proliferation of GMCs, and increase secretion of TGF-β1 , LN. Enalapril can inhibit proliferation of GMCs, and reduce extracelluar matrix（ECM） accumulation, then delay the progression of glomerularsclerosis of diabetic nephropathy.