关键词: 系膜细胞, 结缔组织生长因子, 血管紧张素受体1拮抗剂(AT1Ra), p38丝裂原活化蛋白激酶, cAMP反应元件结合蛋白1

Abstract: Obiective　To investigate the effects of valsartan on the expression of connective tissue growth factor(CTGF)　in rat glomerular mesangial cells under high concentration of glucose .Methods　we used high concentration glucose and valsartan to stimulate the cultured rat glomerular mesangial cells in vitro. The protein expressions of CTGF and the activation of p38 mitogen-activated protein kinase(p38 MAPK) and cAMP response element－bingding protein(CREB1) ) were observed by Western blot. CTGF and fibronectin(FN) mRNA were measured by reverse transcription and polymerase chain reaction (RT- PCR). The protein synthesis of lamanin (LN) and type IV collagen in the supernatants of the GMCs were detected by radioimmunoassay. Results　Compared with low glucose control group, the expression of CTGF,p-p38 MAPK, p-CREB1,CTGF mRNA, FN mRNA, LN and type IV collagen in the supernatants were significantly increased in GMCs under high concentration of glucose medium. The expression levels of CTGF,p-p38 MAPK,p-CREB1 ,CTGF mRNA and FN mRNA were significantly lower in the valsartan group than those in the high concentration glucose group. The concentrations of LN and type IV collagen in the supernatantsin the valsartan group were also lower than those in the hiagh concentration glucose group. Conclusion　 Valsartan can inhibit expression of CTGF and ECM proteins in rat glomerular mesangial cells under high concentration of glucose, partly by regulating the phosphorylation of P38 MAPK and CREB1 .

Key words: angiotensinⅡtypeⅠreceptor antagonist, mesangialcells, high glucose, p38 mitogen-activated Protein Kinase, cAMP response element－bingding protein, connective tissue growth factor