PPARβ及NO在高糖高胰岛素诱导心肌细胞肥大中的作用  

Effects of PPARβ and NO on high glucose and insulin-induced cardiomyocyte hypertrophy

作　　者：黄波[1] 吴阳[1] 薛莱[1] 彭艺飞 邱红梅[1] 蒋青松[1] 

机构地区：[1]重庆医科大学药理教研室,重庆市生物化学与分子药理学重点实验室,重庆400016

出　　处：《中国病理生理杂志》2015年第2期261-266,共6页Chinese Journal of Pathophysiology

基　　金：国家自然科学基金资助项目(No.81100905)

摘　　要：目的:观察过氧化物酶体增殖物激活受体β(PPARβ)及一氧化氮(NO)相关信号通路在高糖高胰岛素(HGI,25.5 mmol/L葡萄糖+0.1μmol/L胰岛素)诱导心肌肥大中的作用。方法:体外培养乳鼠心肌细胞,以细胞表面积、蛋白含量和心房钠尿因子(ANF)mRNA表达作为心肌肥大的指标;利用real-time PCR、Western blotting、硝酸还原酶法和分光光度法分别检测mRNA表达、蛋白表达、NO含量和NO合酶(NOS)活性。结果:HGI诱导心肌细胞出现肥大(P<0.01),PPARβmRNA和蛋白表达明显降低(P<0.05),诱导型NOS(i NOS)mRNA和蛋白的表达则升高(P<0.01),NO含量和NOS活性增加(P<0.01)。PPARβ激动剂GW0742能抑制HGI诱导的心肌肥大(P<0.01),上调PPARβ的表达,降低i NOS的表达,使NOS活性和NO含量恢复正常(P<0.01)。PPARβ拮抗剂GSK0660可阻断GW0742对心肌肥大的保护作用,取消其对PPARβ、i NOS mRNA和蛋白表达水平以及NOS活性和NO含量的作用(P<0.05)。结论:PPARβ下调,激活i NOS-NO信号通路参与高糖高胰岛素诱导心肌肥大过程。AIM： To investigate the role of peroxisome proliferator-activated receptor β（ PPARβ）-nitric oxide（ NO） signal pathway in cardiomyocyte hypertrophy induced by high glucose（ 25. 5 mmol/L） and insulin（ 0. 1 μmol/L）（ HGI）. METHODS： The cardiomyocyte hypertrophy was characterized in rat primary cardiomyocytes by measuring the cell surface area,protein content,and the mRNA expression of atrial natriuretic factor（ ANF）. The mRNA and protein expression were measured by real-time PCR and Western blotting,respectively. The activity of NO synthase（ NOS） and NO content were measured by a reagent kit through ultraviolet spectroscopy. RESULTS： HGI induced profound change of hypertrophic morphology,and significantly increased the cell surface area,protein content and mRNA expression of ANF（ P〈0. 01）,but decreased the expression of PPARβ at mRNA and protein levels（ P〈0. 05）. At the same time,the expression of inducible NOS（ i NOS） was obviously elevated（ P〈0. 01）,which occurred in parallel with the rising NOS activity and NO concentration（ P〈0. 01）. GW0742（ 1 μmol / L）,a selective PPARβ agonist,inhibited the cardiomyocyte hypertrophy induced by HGI（ P〈0. 01）,and up-regulated the expression of PPARβ at both mRNA and protein levels.Meanwhile,GW0742 also inhibited the increases in i NOS expression,NOS activity,and NO content induced by HGI,which were abolished by GSK0660（ 1 μmol / L）,a selective PPARβ antagonist（ P〈0. 01）. CONCLUSION： PPARβdown-regulation and the following i NOS-NO activation are involved in the cardiomyocyte hypertrophy induced by HGI.

关 键 词：过氧化物酶体增殖物激活受体β 诱导型一氧化氮合酶 一氧化氮 心肌肥大 高糖高胰岛素 

分 类 号：R363[医药卫生—病理学] R587.1[医药卫生—基础医学]