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研究HMG-CoA还原酶抑制剂氟伐他汀(fluvastatin)对高糖状态下肾小球系膜细胞中p38丝裂原活化蛋白激酶(p38 mitogen-activated protein kinase,p38MAPK)及其下游因子cAMP反应元件结合蛋白1(cAMP response element-binding protein,CREB1)表达的影响。采用体外培养大鼠肾小球系膜细胞,分别给予高糖和氟伐他汀干预,应用Western blotting检测p38MAPK和CREB1及其磷酸化蛋白(p-p38MAPK、p-CREB1)的表达;逆转录-聚合酶链反应(RT-PCR)检测转化生长因子β1(TGF-β1)和纤维粘连蛋白(FN) mRNA的表达;放射免疫法测定细胞上清液中层连接蛋白(LN)和IV型胶原蛋白的含量。结果表明,与低糖对照组相比,高糖组的系膜细胞p-p38 MAPK、p-CREB1表达明显上调,TGF-β1 mRNA和FNmRNA的表达增加,细胞上清液中LN和IV型胶原蛋白含量增加。氟伐他汀组的p-p38 MAPK、p-CREB1表达明显下调,TGF-β1 mRNA和FN mRNA的表达降低,同时LN和IV型胶原蛋白的含量减少。因此氟伐他汀抑制肾小球系膜细胞TGF-β1的表达和细胞外基质的分泌可能部分是通过影响p38MAPK及其下游因子CREB1的激活而实现的。
To investigate the effect of fluvastatin, a HMG-CoA reductase inhibitor, on the expression of p38 mitogen-activated protein kinase (p38MAPK) and its downstream cAMP response element in mesangial cells (CAMP response element-binding protein, CREB1) expression. The rat glomerular mesangial cells were cultured with high glucose and fluvastatin respectively. Western blotting was used to detect the expression of p38MAPK, CREB1 and phosphorylated protein (p-CREB1). RT-PCR The expression of transforming growth factor β1 (TGF-β1) and fibronectin (FN) mRNA was detected by enzyme linked immunosorbent assay (RT-PCR). The contents of connexin (LN) and collagen IV . The results showed that the expression of p-p38 MAPK and p-CREB1 in mesangial cells was significantly up-regulated and the expressions of TGF-β1 mRNA and FN mRNA were increased compared with those in low glucose control group. The expressions of LN and type IV collagen in supernatant Increased content. In fluvastatin group, the expressions of p-p38 MAPK and p-CREB1 were down-regulated and the expressions of TGF-β1 mRNA and FN mRNA were decreased, while the contents of LN and type IV collagen were decreased. Therefore, the inhibition of fluvastatin on mesangial cells TGF-β1 expression and extracellular matrix secretion may be partly through the impact of p38MAPK and its downstream factor CREB1 activation.