摘要
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。
This study is to investigate the effects of fluvastatin on the activation of p38 mitogen-activated protein kinase （p38 MAPK） and cAMP response element-binding protein （CREB1） in glomerular mesangial cells under high concentration of glucose. High concentration glucose and fluvastatin were used to stimulate the cultured rat glomerular mesangial cells （GMCs） in vitro. The protein expressions of p38 MAPK, CREB1, p-p38 MAPK and p-CREB1 were observed with Western blotting. TGF-β1 and fibronectin （FN） mRNA were measured with reverse transcription and polymerase chain reaction （RT-PCR）. The protein synthesis of laminine （LN） and type IV collagen in the supernatants of the GMCs were detected with radioimmunoassay. Compared with low glucose control group, the expressions of p-p38 MAPK, p-CREB1 were increased obviously in high glucose group, TGF-β1 mRNA and FN mRNA, LN and type IV collagen in the supernatants were increased significantly in GMCs under high concentration glucose medium. The expression levels of p-p38 MAPK, p-CREB1, TGF-β1 mRNA, and FN mRNA, LN and type IV collagen in the supernatants were significantly lower in the fluvastatin group than those in the high concentration glucose group. It is concluded that fluvastatin can inhibit over production of TGF-β1 and ECM proteins in GMCs under high concentration of glucose, partly by regulating the phosphorylation of p38 MAPK and CREB1.
出处
《药学学报》
CAS
CSCD
北大核心
2009年第2期121-125,共5页
Acta Pharmaceutica Sinica
基金
河北省科技攻关课题项目(072761188)
