抑制P53上调GLUT4改善高糖合并缺血缺氧诱导的心肌细胞糖代谢紊乱及减轻细胞凋亡  

Inhibition of P53 and up-regulation of GLUT4 improve glucose metabolism disorder and reduce apoptosis of cardiomyocytes induced by high glucose combined with ischemia-hypoxia

作　　者：张冀鑫 刘芬[2] 张桐 张雪鹤 房彬彬[2] 李晓梅[1] 杨毅宁 ZHANG Jixin;LIU Fen;ZHANG Tong;ZHANG Xuehe;FANG Binbin;LI Xiaomei;YANG Yining(Department of Heart Center,First Affiliated Hospital of Xinjiang Medical University,Urumqi,Xinjiang 830054,China;State Key Laboratory of Pathogenesis,First Affiliated Hospital of Xinjiang Medical University,Urumqi,Xinjiang 830054,China;Department of Cardiology,People's Hospital of Xinjiang Uygur Autonomous Region,Urumqi,Xinjiang 830001,China)

机构地区：[1]新疆医科大学第一附属医院心脏中心,新疆乌鲁木齐市830054 [2]新疆医科大学第一附属医院心血管重点实验室,新疆乌鲁木齐市830054 [3]新疆维吾尔自治区人民医院心内科,新疆乌鲁木齐市830001

出　　处：《中国动脉硬化杂志》2023年第3期212-217,共6页Chinese Journal of Arteriosclerosis

基　　金：新疆维吾尔自治区高校科研计划项目(XJEDU2021I015);省部共建中亚高发病成因与防治国家重点实验室开放课题(SKL-HIDCA-2020-2);新疆医科大学研究生科研创新项目(CXCY2022006)。

摘　　要：[目的]探讨抑制心肌细胞P53,增加葡萄糖转运体4(GLUT4)表达,能否改善高糖(HG)合并缺血缺氧(IH)诱导的心肌细胞糖代谢紊乱,减轻细胞凋亡。[方法]建立体外HG+IH心肌细胞模型,实验分为:对照组、HG组、IH组、HG+IH组、HG+IH+P53抑制剂组(HG+IH+Pifithrin-α组)、HG+IH+P53抑制剂+GLUT4抑制剂组(HG+IH+Pifithrin-α+Fasentin组)。CCK-8法检测细胞活力,试剂盒检测乳酸脱氢酶(LDH)、糖酵解关键酶活性和ATP含量,Western blot检测P53、GLUT4、Bax/Bcl-2和Caspase-3的蛋白表达,流式细胞仪检测心肌细胞凋亡。[结果](1)体外HG+IH心肌细胞模型中,与对照组比较,心肌细胞P53表达增加75%,GLUT4表达减少16%,细胞ATP含量下降51%,细胞活力减低45%,LDH活性增加3.6倍,Caspase-3和Bax/Bcl-2表达分别增加54%和77%,细胞凋亡率增加(P均<0.05)。(2)抑制心肌细胞P53表达后,与HG+IH组比较,HG+IH+Pifithrin-α组心肌细胞GLUT4表达增加34%,细胞ATP含量增加60%,细胞活力增加50%,LDH活性减低13%,Caspase-3和Bax/Bcl-2表达分别减少31%和53%,细胞凋亡率下降(P均<0.05)。(3)在抑制GLUT4后,与HG+IH+Pifithrin-α组比较,HG+IH+Pifithrin-α+Fasentin组GLUT4表达减少22%,细胞内ATP含量减少39%,细胞存活力减低25%,LDH活性增加21%,Caspase-3和Bax/Bcl-2表达分别增加43%和89%,细胞凋亡率增加(P均<0.05)。[结论]在高糖合并缺血缺氧心肌细胞模型中,抑制P53可增加GLUT4表达,改善高糖合并缺血缺氧诱导的心肌细胞糖代谢紊乱,减轻细胞凋亡。Aim To explore whether inhibiting P53 and increasing the expression of glucose transporter 4(GLUT4) in cardiomyocytes can improve glucose metabolism disorder and reduce apoptosis induced by high glucose(HG) combined with ischemia-hypoxia(IH). Methods The cardiomyocyte HG+IH model was induced in vitro. The experimental groups were the control group, HG group, IH group, HG+IH group, HG+IH+P53 inhibitor group(HG+IH+Pifithrin-α group), HG+IH+P53 inhibitor+GLUT4 inhibitor group(HG+IH+Pifithrin-α+Fasentin group). Cell viability was detected by the CCK-8 method, lactate dehydrogenase(LDH), glycolytic key enzyme activity, and ATP content were detected by the kit, protein expression of P53, GLUT4, Bax/Bcl-2 and Caspase-3 were detected by Western blot, and cardiomyocyte apoptosis was detected by flow cytometry. Results(1)In the HG+IH cardiomyocyte model in vitro, compared with the control group, the expression of P53 increased by 75%, the expression of GLUT4 decreased by 16%, the content of ATP decreased by 51%, the cell viability decreased by 45%, the LDH activity increased by 3.6 times, the expression of Caspase-3 and Bax/Bcl-2 increased by 54% and 77% respectively, and the apoptosis rate increased(all P<0.05).(2)After inhibiting the expression of P53 in cardiomyocytes, compared with the HG+IH group, the expression of GLUT4 in cardiomyocytes increased by 34%, the content of ATP increased by 60%, the cell viability increased by 50%, the LDH activity decreased by 13%, the expression of Caspase-3 and Bax/Bcl-2 decreased by 31% and 53% respectively, and the apoptosis rate decreased in HG+IH+Pifithrin-α group(all P<0.05).(3)After inhibiting GLUT4, compared with the HG+IH+Pifithrin-α group, the expression of GLUT4 in cardiomyocytes decreased by 22%, the content of ATP decreased by 39%, the cell viability decreased by 25%, the LDH activity increased by 21%, the expression of Caspase-3 and Bax/Bcl-2 increased by 43% and 89% respectively, and the apoptosis rate increased(all P<0.05).Conclusions In the cardiomyocyte model of h

关 键 词：P53 葡萄糖转运体4 高糖合并缺血缺氧 糖代谢紊乱 细胞凋亡 

分 类 号：R363[医药卫生—病理学] R5[医药卫生—基础医学]