福辛普利对血管紧张素Ⅱ下调大鼠肾小管上皮细胞klotho基因表达的干预作用  

Fosinopril up-regulates and ameliorates the Ang Ⅱ induced down-expression of klotho gene in NRK-52E

作　　者：林书典[1] 周巧玲[2] 詹锋[1] 陈道军[1] 李文宁[1] 

机构地区：[1]海南省人民医院肾病内科,海口570001 [2]中南大学湘雅医院肾病内科,湖南长沙410008

出　　处：《中国应用生理学杂志》2010年第3期348-351,共4页Chinese Journal of Applied Physiology

基　　金：海南省自然科学基金资助项目(309087)

摘　　要：目的:研究福辛普利(fosinopril,Fos)对klotho基因表达的影响,探讨Fos对AngⅡ下调klotho基因表达的影响机制。方法:大鼠肾小管上皮细胞(NRK-52E)与干预药物共培养。按Fos时间梯度0(对照组),3,6,12,24h和浓度梯度0(对照组),10-9,10-8,10-7,10-6,10-5mol/L分组培养,用逆转录-多聚酶链反应(RT-PCR)检测klotho mRNA表达水平;设A.对照组,B.AngII(10-7mol/L)组,C.Fos(10-5mol/L)组,D.Fos(10-5mol/L)+AngII(10-7mol/L)组,E.Fos(10-5mol/L)干预12h后+AngII(10-7mol/L)共培养组,培养24h,用RT-PCR和免疫组化法检测klotho mRNA和蛋白表达。结果:①Fos对klotho mRNA表达呈时效依赖关系(P<0.05),而量效关系不明显(P>0.05);②AngII可抑制klotho mRNA和蛋白表达,给予Fos和AngII共同作用,或Fos预先干预后均能抑制AngII下调klotho mRNA表达,组间比较差异具有显著性意义(P均<0.05)。结论:Fos对klotho mRNA表达存在时效依赖关系,Fos可能对klotho mRNA和蛋白表达起上调作用,并能抑制AngⅡ对klotho mRNA和蛋白的下调表达。Objective： To investigate the effect of fosinopril （Fos） on regulating klotho gene expression and elucidate the mechanism of Fos regulating the Angiotensin II （AngII） -induced down-expression of klotho gene. Methods： Culture cells, NRK-52E, were incubated with media either AnglI or Fos or both of all. Experimental groups incubated with Fos （ 10.5 mol/L） were divided according to variant points of time for 0 （control） ,3,6,12,24 h. Different concentration of Fos was selected to incubated with culture cells for 0 （control）, 10^-9, 10^-8, 10^-7, 10^-6, 10^-5 mol/L at the optimal time point （24 h）. Five groups, which were A： control; B： AngII（ 10^-7 moL/L） ; C： Fos（ 10^-5 mol/L） ; D： AngⅡ（10^-7 tool/L） ＋ Fos（ 10^-5 mol/L）and E： Cells pretreated with Fos（ 10^-5 tool/L）12 h incubated with AngII（ 10^-7 mol/L） were divided to observe the effect of Fos on expression of ldotho induced by AngII. RT-PCR and immunohistochemistry（IHC） were applied to evaluate the klotho mNA and protein expression, respectively. Results： Fos up-regulated klotho mRNA in time-dependent manner, and independent of dose-de- pendent manner; AngII obviously decreased the levels of kloltho mRNA and protein expression in NRK-52E as compared to the control（ P 〈 0.05）, the down-regulating effect was reversed by incubating both with AngII and Fos（ P 〈 0. 05）, and Fos could inhibit the down-regulated expression of klotho gene induced by Ang Ⅱ in NRK-52E. Conclusion： Fosinopril up-regulates klotho mRNA in time-dependent manner, and inhibits the down-regulated expression of klotho gene induced by Ang Ⅱ.

关 键 词：KLOTHO基因 福辛普利 血管紧张素Ⅱ 

分 类 号：R969[医药卫生—药理学]