哌立福新对心肌细胞缺血再灌注损伤的保护作用及机制探讨

发布时间：2018-04-26 01:34

本文选题：氧-葡萄糖剥夺 + 心肌细胞　；参考：《南京医科大学》2016年博士论文

【摘要】：研究目标：哌立福新是一种Akt抑制剂,令人惊讶的是我们发现低浓度哌立福新具有保护心肌免受氧葡萄糖剥夺(OGD)/再氧合作用,本项目的实验目的是进一步探索哌立福新对心肌细胞缺血再灌注损伤的保护作用及该保护作用的可能机制。实验方法和结果：1.检测不同浓度的派立福辛对H9c2细胞存活的影响,并检测经低浓度(0.1-0.5μM)哌立福新处理后不同作用时间H9c2细胞的活力,发现低浓度派立福辛对心肌细胞有保护作用,而且低浓度哌立福新可以保护H9c2细胞受到的氧糖剥夺/再氧合损伤。2.检测低浓度派立(0.1-0.5μM)福辛对氧糖剥夺诱导活性氧、线粒体Cyp-D-p53结合物及线粒体膜电位(MMP)的影响,表明低浓度派立福辛可抑制糖剥夺/再氧合引起的氧化应激反应。3.检测AMPK信号通路在低浓度哌立福新(0.1-0.5μM)保护心肌细胞中的作用,并通过构建慢病毒shRNA转染H9c2细胞及对新生小鼠心肌细胞使用AMPKal siRNA敲除基因来抑制AMPK,发现哌立福新介导的抗氧化与细胞保护作用被大大减弱。实验结论：低浓度哌立福新(0.1-0.5 gM)在H9c2细胞受到的氧糖剥夺／再氧合发生损伤时起保护作用。其机制可能与低浓度派立福辛能通过诱导AMPK信号通路激活,对抗氧糖剥夺／再氧合介导抗氧化有关。本研究提示低浓度的哌立福新有可能成为临床上治疗心肌缺血再灌注损伤的一种新的方法。
[Abstract]:Objective: piperidoxin is a Akt inhibitor, and surprisingly, we found that low concentrations of pirifoxacin can protect myocardium from oxygen and glucose deprivation and can be used in combination with OGDX / reoxygenation. The aim of this study was to explore the protective effect of pirifoxacin on myocardial ischemia-reperfusion injury and its possible mechanism. Experimental methods and results: 1. The effects of different concentrations of pirifampicin on the survival of H9c2 cells were detected, and the viability of H9c2 cells treated with low concentration of pirifoxacin 0.1-0.5 渭 m for different time was detected. It was found that low concentration of pirifampicin had protective effect on cardiomyocytes. And the low concentration of piperfon can protect H9c2 cells from oxygen glucose deprivation / reoxygenation injury. 2. The effects of low concentration of piridol 0.1-0.5 渭 M) on oxygen glucose deprivation induced reactive oxygen species (Ros), mitochondrial Cyp-D-p53 conjugates and mitochondrial membrane potentials (mMPs) were determined, indicating that low concentration of pirifampicin could inhibit oxidative stress induced by glucose deprivation / reoxygenation. The role of AMPK signaling pathway in the protection of cardiomyocytes from 0. 1-0. 5 渭 M of piprafon at low concentration was detected. By constructing lentivirus shRNA to transfect H9c2 cells and using AMPKal siRNA knockout gene to inhibit AMPK in neonatal mouse cardiomyocytes, it was found that the antioxidation and cell protection mediated by piperidoxin were greatly weakened. Conclusion: the low concentration of pirifampicin 0.1-0.5 g M may protect H9c2 cells from oxygen glucose deprivation / reoxygenation injury. The mechanism may be related to the low concentration of parifoxine by inducing activation of AMPK signaling pathway, and antagonizing oxygen glucose deprivation / reoxygenation mediated oxidation. This study suggests that low-concentration piperidoxacin may be a new method for the treatment of myocardial ischemia-reperfusion injury.
【学位授予单位】：南京医科大学
【学位级别】：博士
【学位授予年份】：2016
【分类号】：R542.2

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