去甲肾上腺素及血管紧张素Ⅱ对大鼠心肌细胞胰岛素受体及胰岛素受体底物1酪氨酸磷酸化的综合效应  

Comprehensive effect of norepinephrine and angiotensin Ⅱ on the tyrosine phosphorylation of insulin receptor and insulin receptor substance 1 in rat cardiac cells

作　　者：刘扬[1] 李竹琴[2] 张志刚[3] LIU Yang;LI Zhu-qin;ZHANG Zhi-gang(Department of General Medicine, The Hospital of Northeast Agricultural University, Harbin Heilongjiang 150030;Department of Cardiovascular, The First Affiliated Hospital of Harbin Medical University,Harbin Heilongjiang 150001;College of Veterinary Medicine, Northeast Agricultural University, Harbin Heilongjiang 150030, China)

机构地区：[1]东北农业大学医院内科,黑龙江哈尔滨150030 [2]哈尔滨医科大学附属第一医院心内科,黑龙江哈尔滨150001 [3]东北农业大学动物医学学院,黑龙江哈尔滨150030

出　　处：《蚌埠医学院学报》2018年第2期146-149,共4页Journal of Bengbu Medical College

基　　金：黑龙江省青年基金面上项目(QC 2010057)

摘　　要：目的:初步探讨去甲肾上腺素(NE)与血管紧张素Ⅱ(AngⅡ)对大鼠心肌细胞胰岛素受体β亚基(Ins-Rβ)及胰岛素受体底物1(IRS-1)酪氨酸磷酸化的综合效应,以及心肌胰岛素抵抗的机制。方法:培养新生大鼠心肌细胞。按照浓度梯度,将相同浓度的NE与AngⅡ的混合液加入培养基中,培养72 h后,采用Western blotting法检测胰岛素信号分子蛋白表达水平。另于每个实验组中加入AngⅡ受体阻断剂氯沙坦,分别观察NE与AngⅡ的独立效应。结果:相同浓度的NE与AngⅡ混合液可引起心肌细胞Ins-R、IRS-1及葡萄糖转运体4(GLUT4)等蛋白表达减少,Ins-Rβ亚基酪氨酸磷酸化等蛋白表达减少,IRS-1酪氨酸磷酸化蛋白表达增加(P<0.05)。1μmol/L氯沙坦对Ins-Rβ亚基酪氨酸磷酸化蛋白表达无显著影响(P>0.05),可减少IRS-1酪氨酸磷酸化蛋白表达(P<0.05)。结论:相同浓度的NE与AngⅡ的共同作用可降低大鼠心肌细胞Ins-Rβ酪氨酸磷酸化水平,升高IRS-1酪氨酸磷酸化水平。NE为引起Ins-Rβ酪氨酸磷酸化水平降低的主要原因,AngⅡ升高为IRS-1酪氨酸磷酸化水平升高的主要原因。Objective： To investigate the comprehensive effects of norepinephrine（ NE） and angiotensin Ⅱ（ Ang Ⅱ） on tyrosine phosphorylation of insulin receptor β（ Ins-Rβ） subunit and insulin receptor substance 1（ IRS-1） in rat cardiac cells,and the mechanism of insulin resistance. Methods： The myocardial cells from the neonatal rat（ 1 to 3 d） were primary cultured,and co-cultured with the same concentration of the mixture of NE and AngⅡ for 72 h according to the concentration gradient. The protein expressions of insulin signal molecules were detected using Western blotting. Losartan,Ang Ⅱ receptor blockers,was added into each experiment group,and the independent effect of NE and AngⅡ was observed. Results： Under the same concentration of the mixture of NE and Ang Ⅱ,the protein expression levels of Ins-R,IRS-1 and glucose transporter type 4（ GLUT4）,and level of tyrosine phosphorylation of Ins-Rβdecreased,and the level of tyrosine phosphorylation of IRS-1 increased in myocardial cells（ P 〈0. 05）. The effect of 1 μmol/L of losartan on the level of tyrosine phosphorylation of Ins-Rβ was not obvious（ P〉 0. 05）,which could decrease the level of tyrosine phosphorylation of IRS-1（ P 〈0. 05）. Conclusions： The same concentration of the mixture of NE and AngⅡ can decrease the tyrosine phosphorylation level of Ins-R β subunit,and increase the tyrosine phosphorylation level of IRS-1. NE is the crucial factor in decreasing the tyrosine phosphorylation level of Ins-Rβ,and the AngⅡ is the crucial factor in increasing the tyrosine phosphorylation level of IRS-1.

关 键 词：胰岛素抵抗 去甲肾上腺素 血管紧张素Ⅱ 酪氨酸磷酸化 

分 类 号：R361.3[医药卫生—病理学]