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作 者:叶红伟[1] 张蔚屏[1] 胡俊锋[2] 于影[1] 方婷婷[1] 杨丽娟[1] 高琴[1] YE Hong-wei;ZHANG Wei-ping;HU Jun-feng;YU Ying;FANG Ting-ting;YANG Li-juan;GAO Qin(I.Department of Physiology,Bengbu Medical College,Bengbu Anhui 23003;Respiratory Intensive Care Unit,The First Affiliated Hospital of Bengbu Medical College,Bengbu Anhui 233004,China)
机构地区:[1]蚌埠医学院生理学教研室,安徽蚌埠233030 [2]蚌埠医学院第一附属医院呼吸与危重症监护科,安徽蚌埠233004
出 处:《蚌埠医学院学报》2018年第10期1355-1358,共4页Journal of Bengbu Medical College
基 金:国家自然科学基金面上项目(81770297);安徽高校自然科学研究重点项目(KJ2017A221;KJ2018A1025)
摘 要:目的:观察Hippo信号通路效应蛋白YAP在糖尿病大鼠心肌肥大中的改变,分析可能的作用机制。方法:健康雄性SD大鼠随机分为2组,每组6只。正常对照组:大鼠正常饮水饮食喂养12周;糖尿病心肌病组:大鼠腹腔注射STZ(55 mg/kg)复制糖尿病模型,以血糖≥16.7 mmo1/L,持续1周确定造模成功,继续饲养12周。测定大鼠空腹血糖水平和体质量;心室内插管检测左心室动力学变化,称量心脏质量计算心体比;荧光定量PCR检测心肌肥大相关基因心房钠尿肽和脑利钠肽mRNA表达,Western blot法检测YAP和p-YAP蛋白表达改变。结果:与正常对照组相比,糖尿病组大鼠心体比增加,左心室舒张末压增高,左心室发展压、左心室内压最大上升和下降速率及左心室做功均降低;心肌肥大相关基因心房钠尿肽和脑利钠肽mRNA表达增加;YAP蛋白表达增加,p-YAP/YAP比值降低(P<0.05~P<0.01)。结论:糖尿病可诱导心肌肥大,其机制可能与增加Hippo信号通路效应蛋白YAP的表达,降低其磷酸化水平有关。Objective:To observe the changes of YAP, the effector protein of Hippo pathway, in rat model with myocardial hypertrophy induced by diabetes, and analyze its possible mechanism. Methods : Twelve healthy male SD rats were randomly divided into the nonnal control group and diabetic cardiomyopathy group(6 rats each group). The normal control group was ted with nonnal water and diet tor 12 weeks,the diabetes model with blood glucose level ≥16.7 mmol/L for 1 week was established successtully by intraperitoneal injec-tion of STZ(55 mg/kg), and ted for 12 weeks. In two groups, the tasting blood glucose level and body weight were measured, the lefl ventricle dynamics was detected through intraventricular intubation, and the ratio of heart to body weight was calculated by weighing heart. The expression levels of cardiac hypertrophy related gene atrial natriuretic tactor(ANF) and brain natriuretic peptide (BNP) mR-NA were detected using fluorescence quantitative PCR,and the expression levels of YAP and p-YAP protein level were detected using Western blot. Results : Compared with the nonnal control group, the ratio of heart to body increased, the left ventricular end-diastolic blood pressure increased, the rate of rise and fa11 of the maximum lefl ventricular development pressure decreased, and the lefl ventricu-lar doing work decreased in diabetic cardiomyopathy group. The expression levels of ANF and BNP mRNA increased, the YAP protein expression increased and the ratio of p-YAP/YAP decreased. Conclusions : Diabetes can induce myocardial hypertrophy, the mechanism of which may be related to the increasing of YAP protein expression in Hippo signaling pathway to decrease of the phosphorylation lev-el.
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