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。
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（P0.05）.Compared to HG,fluvastatin increased klotho expression（P0.05）.The effect of fluvastatin on klotho protein was abrogated by MVA and GGPP,but not by FPP,meanwhile fluvastatin inhibited HG-induced RhoA expression（P0.05）.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.
出处
《江苏医药》
CAS
CSCD
北大核心
2010年第13期1558-1561,共4页
Jiangsu Medical Journal
