替米沙坦对心肌细胞脂联素受体1表达的影响及其可能机制研究  

Effects of telmisartan on the expression of adiponectin receptor 1 in cardiomyocytes and its mechanism

作　　者：吴杰萍[1] 郭志新[1] 

机构地区：[1]山西医科大学第二医院内分泌科,太原030001

出　　处：《解放军医学杂志》2015年第1期30-34,共5页Medical Journal of Chinese People's Liberation Army

基　　金：山西医科大学科技创新基金(01201015);山西省回国留学人员科研资助项目(2011-048);山西省自然科学基金(2013011047-1);山西省留学人员科技活动择优资助项目(2012年批准)~~

摘　　要：目的探讨替米沙坦调节糖尿病心肌细胞脂联素受体1表达的作用机制。方法取H9C2心肌细胞作为研究对象,分两个部分进行实验。第一部分检测血管紧张素Ⅱ(AngⅡ)抑制的影响:以不同浓度(0、10-8、10-7、10-6、10-5mol/L)AngⅡ作用48h以及AngⅡ(10-7mol/L)作用不同时间(0、12、24、36、48h)后检测心肌细胞内脂联素受体1 m RNA和蛋白的表达;以10-5mol/L替米沙坦孵育1h,然后用10-7mol/L AngⅡ培养24h后检测前述指标的表达。第二部分检测过氧化物酶体增殖物活化受体-γ(PPAR-γ)激活的影响:将H9C2心肌细胞分5组:1对照组(NG组);2高糖组(HG组);3高糖+替米沙坦组(HG+T组);4高糖+替米沙坦+PPAR-γ抑制剂GW9662组(HG+T+GW组);5低糖+甘露醇组(NG+M组)。按分组处理24h后检测心肌细胞脂联素受体1 m RNA和蛋白的表达。采用实时荧光定量聚合酶链反应法和免疫印迹法测定心肌细胞脂联素受体1 m RNA和蛋白的表达。结果在AngⅡ浓度为10-8、10-7、10-6、10-5mol/L时心肌细胞脂联素受体1 m RNA和蛋白表达均明显降低(P<0.05),尤以10-7mol/L时下降最显著(P<0.01)。10-7mol/L AngⅡ作用12、24、36、48h后心肌细胞脂联素受体1 m RNA和蛋白表达均明显降低(P<0.05),尤以24h下降最显著(P<0.01)。替米沙坦可显著上调AngⅡ作用后的心肌细胞脂联素受体1 m RNA和蛋白表达(P<0.05)。与NG组比较,HG组心肌细胞脂联素受体1 m RNA和蛋白表达显著降低(P<0.05),而NG+M组表达无显著变化(P>0.05)。与HG组比较,HG+T组心肌细胞脂联素受体1m RNA和蛋白表达显著升高(P<0.05);与HG+T组比较,HG+T+GW组心肌细胞脂联素受体1 m RNA和蛋白表达显著降低(P<0.05)。结论高糖和AngⅡ可显著降低心肌细胞脂联素受体1的表达。替米沙坦通过激活PPAR-γ、抑制AngⅡ而上调高糖培养的心肌细胞脂联素受体1的表达。Objective To explore the mechanisms of telmisartan in regulating the expression of adiponectin receptor 1 （AdipoRl） in diabetic cardiomyocytes. Methods Investigation of the inhibitory effects of Ang Ⅱ were performed in 3 sub- experiments as follows： One detects mRNA and protein expression of AdipoR1 in different batches of H9C2 cells pre-treated with Ang Ⅱ for 48 hours at a concentration of 0, 108, 107, 106, 10-5mol/L respectively, one in cells pre-treated with Ang H at a concentration of 10-7mol/L for 0, 12, 24, 36 and 48 hours respectively, while the last in ceils pre-treated with telmisartan at 10 Smol/L for 1 hour followed by Ang Ⅱ at 10-7mol/L for 24 hours. Cultured H9C2 cardiomyocytes were randomly divided into following five groups： normal control group （NG）, high glucose group （HG）, high glucose plus telmisartan group （HG＋T）, high glucose plus telmisartan and PPAR-y antagonist GW9662 group （HG＋T＋GW）, and normal glucose plus mannitol group （NG＋M）. Cardiomyocytes in the above-mentioned five groups were continued to be cultured for 24h, then the mRNA and protein expressions of AdipoR1 in cardiomyocytes were assayed. Fluorescent quantitative real-time PCR and Western blotting were used respectively to analyze the mRNA and protein expressions of AdipoR1 in cardiomyocytes. Results The mRNA and protein expressions of AdipoR1 in cardiomyocytes were significantly decreased by Ang Ⅱ at concentrations of 10-8, 10-7, 10-6 and 10-5mol/L （P〈0.05）, reaching a maximal decrease at concentration of 10-7mol/L （P〈0.01）. The mRNA and protein expressions of AdipoR1 were significantly down-regulated in cardiomyocytes after being incubated with Ang Ⅱ for 12h, 24h, 36h and 48h, reaching a maximal down-regulation at 24h （P〈0.01）. Telmisartan significantly up-regulated the mRNA and protein expressions of AdipoR1 in cardiomyocytes treated with Ang Ⅱ （P〈0.05）. Compared with group NG, group HG showed a significant down-regulation in the mRNA and protein expression

关 键 词：替米沙坦 PPARΓ 血管紧张素Ⅱ 肌细胞 心脏 受体 脂联素 

分 类 号：R587.1[医药卫生—内分泌]