摘要
目的 :观察HMG CoA还原酶抑制剂洛伐他汀对人肾小球系膜细胞胰岛素样生长因子 1(IGF 1)表达及纤维连接蛋白、层连蛋白和Ⅳ型胶原分泌的影响。方法 :分别于体外低糖 (5 6mmol/L)和高糖 (3 0mmol/L)环境中培养人胎肾小球系膜细胞 ,用RT PCR法检测系膜细胞IGF 1mRNA表达水平 ,用酶免和放免法测定细胞上清液中纤维连接蛋白、层黏连蛋白和Ⅳ型胶原含量。分别在培养液中加入洛伐他汀或 /和西拉普利 ,观察不同刺激时间和药物浓度对上述基质蛋白指标的影响。选择刺激时间 48h和刺激浓度 10 μmol/L ,观察单用或联用洛伐他汀和西拉普利对系膜细胞IGF 1mRNA表达的影响。结果 :高糖环境下肾小球系膜细胞过度增殖 ,细胞上清液中纤维连接蛋白、层黏连蛋白和Ⅳ型胶原含量增加 ,IGF 1mRNA表达明显增加。洛伐他汀和西拉普利均可明显抑制系膜细胞增殖 ,降低细胞上清液中基质蛋白浓度 ,IGF 1mRNA表达亦显著下降。洛伐他汀对IGF 1mRNA表达的抑制作用略强于西拉普利 ,但两者联用未显示更强的抑制效果。结论 :高糖可刺激人肾小球系膜细胞IGF 1高表达 ,并增加基质蛋白的分泌 ,洛伐他汀与西拉普利类似 ,均可一定程度逆转上述现象 ,提示他汀类药物可能有益于早期糖尿病肾病的防治。
AIM:To observe the effect of lovastatin(statin) on the expression of insulin-like growth factor-1(IGF-1) in the cultured h uma n mesangial cells and the secretion of fibronectin,laminin and type IV collage n proteins from them METHODS: The human mesangial cells was respecti vely cultur ed in the medium with low glucose(5 6 mmol/L) and high glucose(30 mmol/L) T he expression of IGF-1 mRNA in mesangial cells were observed by RT-PCR method an d the concentrations of fibronectin,laminin and type IV collagen in the supernat a nt were determined by ELISA and radioimmunoassay methods The extracelluar matr i x(ECM) proteins in the supernatant were detected again after addition of lovasta tin,cilazapril and both of them on different stimulation time and dosage Th e IGF-1 mRNA expression of mesangial cells were also detected on 48 h after stimu l ation of lovastatin(10 μmol/L) and cilazapril(10 μmol/L) RESULTS: High glucos e induced over proliferation of mesangial cells,excessive IGF-1 mRNA expressi on and the increased secretion of fibronection,laminin and type IV collagen of m e sangial cells Both lovastatin and cilazapril decreased the cell proliferation , the IGF-1 mRNA expression and the level of above extracellular matrix(ECM) pro t eins Lovastatin has more suppressive effect on the expression of IGF-1 mRNA th an cilazapril But combination of them has no more suppressive effect than that single of them CONCLUSIONS: High glucose stimulates the cultured hu man mesangial c e lls to excessively express the IGF-1 and ECM proteins The high glucose-induc ed changes can be suppressed by lovastatin and cilazapril The results suggest tha t statin has a direct cellular impact on the expression of IGF-1 of mesangial ce l ls They also indicate that statin have potential preventive action for diabeti c nephropathy
出处
《中国药科大学学报》
CAS
CSCD
北大核心
2003年第6期524-528,共5页
Journal of China Pharmaceutical University
基金
国家"九五"科技攻关计划资助项目 (No .96 90 6 0 5 0 )
