PPARβ在虎杖苷抗高糖高胰岛素诱导心肌肥大中的作用  

PPARβ-related signal pathway involves in the effect of polydatin on high glucose-and insulin-induced cardiomyocyte hypertrophy

作　　者：黄波[1] 江芬 薛莱[1] 吴阳[1] 杜为民[1] 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 [2]湖北省蕲春县人口和计划生育服务中心,湖北蕲春436300

出　　处：《中国药理学通报》2015年第9期1264-1269,共6页Chinese Pharmacological Bulletin

基　　金：国家自然科学基金资助项目(No 81100905)

摘　　要：目的观察虎杖苷(polydatin,PD)对高糖高胰岛素[(high glucose and insulin,HGI)葡萄糖25.5 mmol·L-1+胰岛素0.1μmol·L-1]诱导心肌肥大的影响,并探讨过氧化物酶体增殖物激活受体β(peroxisome proliferator activated receptors-β,PPARβ)、核转录因子κB(nuclear transcription factor-κB,NF-κB)及一氧化氮(nitric oxide,NO)相关信号通路在其中可能存在的作用。方法体外培养乳鼠心肌细胞,以细胞表面积、蛋白含量和心房利钠因子(atrial natriuretic factor,ANF)mRNA表达作为心肌细胞肥大反应指标;利用qRT-PCR、Western blot法分别检测PPARβ、NF-κB p65及诱导型一氧化氮合酶(induced nitric oxide synthase,i NOS)mRNA及蛋白表达,硝酸还原酶法和分光光度法分别检测NO含量和NOS活性。结果 HGI作用下,细胞表面积增大、总蛋白含量增加、ANF mRNA表达升高(P<0.01),出现明显的心肌肥大;同时,PPARβ表达降低,而NF-κB p65、i NOS表达明显升高;总NOS活性及NO含量亦增加(P<0.01)。PD(0.1、1、10μmol·L-1)明显抑制HGI诱导的心肌细胞肥大(P<0.01);并逆转HGI对PPARβ及NF-κB p65、i NOS表达和总NOS活性、NO含量的影响。PPARβ选择性阻断剂GSK0660可阻断PD对心肌肥大的保护,取消其上述作用(P<0.05)。结论 PD对HGI诱导的心肌肥大具有保护作用,其机制可能与其上调PPARβ表达,抑制NF-κB-i NOS-NO信号通路激活有关。Aim To investigate the effect of polydatin on cardiomyocyte hypertrophy induced by high glucose（ 25. 5 mmol·L- 1） and insulin（ 0. 1 μmol ·L- 1）（ HGI） and its possible influence on peroxisome proliferator-activated receptor-β（ PPARβ） / nuclear transcription factor-κB（ NF-κB） / nitric oxide（ NO） signaling pathway. Methods The cardiomyocyte hypertrophy was characterized in rat primary cardiomyocytes by measuring the cell surface area,protein content,and atrial natriuretic factor（ ANF） mRNA expression. The mRNA and protein expressions were measured by qRTPCR and Western blotting,respectively. The activity of NO synthase（ NOS） and NO content were measured by reagent kit through ultraviolet spectroscopy. Results HGI significantly induced cardiomyocyte hypertrophy which increased the cell surface area,protein content and ANF mRNA expression（ P〈0. 01）. Meanwhile,the expressions of PPARβ mRNA and protein reduced while the NF-κB p65 and i NOS expressions increased significantly which occurred in parallel with rising NOS activity and NO concentration（ P〈0. 01）. Polydatin（ 0. 1,1,10 μmol·L- 1） inhibited the cardiomyocyte hypertrophy induced by HGI（ P〈0. 01）,and reversed the mRNA and protein expressions of PPARβ,NF-κB p65 and i NOS,and NOS activity,as well as NO content. These effects of polydatin were abolished by GSK0660（ 1 μmol·L- 1）,a selective PPARβ antagonist（ P〈0. 05）. Conclusion Polydatin resists HGI-induced cardiomyocyte hypertrophy, which may be mediated by PPARβ up-regulation,and then NF-κB-i NOS-NO pathway inactivation.

关 键 词：虎杖苷 心肌肥大 高糖高胰岛素 PPARβ NF-ΚB 一氧化氮 糖尿病 

分 类 号：R-332[医药卫生] R284.1