【摘要】 目的探讨高糖(HG)及氟伐他汀对人肾小管上皮细胞2(HK-2)klotho蛋白表达的影响及机制。方法正常糖(NG,5.5mmol/L),HG(25.0mmol/L)培养HK-2,不同浓度氟伐他汀(0.1、1.0、10μmol/L)伴/不伴甲羟戊酸(MVA)、焦磷酸牛龙牛儿基牛龙牛儿酯(GGPP)、焦磷酸法尼酯(FPP),干预不同时间(0、12、24、48h),Western blot检测klotho、RhoA蛋白表达。结果与NG培养比较,HG刺激HK-2表达klotho蛋白量明显减少(P<0.05);氟伐他汀干预后部分恢复(与HG刺激比较,P<0.05);此作用可被MVA、GGPP逆转,FPP不能逆转。HK-2RhoA蛋白量在HG刺激下增加(与NG培养比较,P<0.05),氟伐他汀干预后表达减少(P<0.05)。结论 HG抑制HK-2klotho蛋白表达;氟伐他汀上调HK-2表达klotho蛋白,机理可能与其抑制RhoA/Rho激酶信号通路有关。更多还原

【Abstract】 Objective To investigate the effects of fluvastatin and high glucose(HG) on klotho protein expression of human renal tubular epithelial cell-2(HK-2).Methods HK-2 cells were incubated with normal glucose(NG,5.5mmol/L),HG(25.0mmol/L),fluvastatin in different concentrations(0.1,1.0,10μmol/L) for different time (0,12,24,48h) with or without MVA,GGPP,FPP.The protein expressions of klotho and RhoA were detected by Western blotting.ResultsCompared to NG,HG decreased the level of klotho protein expression(P<0.05).Compared to HG,fluvastatin increased klotho expression(P<0.05).The effect of fluvastatin on klotho protein was abrogated by MVA and GGPP,but not by FPP,meanwhile fluvastatin inhibited HG-induced RhoA expression(P<0.05).Conclusion HG decreases the expression of klotho protein.Fluvastatin up-regulates klotho expression from HK-2 through inhibiting RhoA/Rho kinase pathway activated by HG.更多还原