MAPK信号通路通过内质网应激反应调控梗死后心力衰竭小鼠心肌细胞凋亡

发布时间：2018-05-19 16:40

本文选题：MAPK信号通路 + 心肌细胞凋亡　；参考：《基因组学与应用生物学》2017年08期

【摘要】：本研究旨在评估MAPK信号通路在梗死后心力衰竭期间调节心肌细胞凋亡中的作用及其可能的潜在机制。通过左前降支冠状动脉闭塞诱发构建梗死后心力衰竭的小鼠模型,通过组织化学和ELISA分别测定血清中心肌梗死面积和肌酸激酶-MB(CK-MB)和心肌肌钙蛋白(c Tn I)水平。此外,评估了氧-葡萄糖剥夺/恢复(OGD/R)对具有和不具有MAPK抑制剂PD-98059预处理的心肌细胞的直接细胞毒性作用。分别采用MTT、ELISA和流式细胞术测定PD-98059对细胞活力、乳酸脱氢酶(LDH)释放和细胞凋亡的影响。采用RT-PCR和Western blotting检测内质网(ER)应激标志物如葡萄糖调节蛋白78、CCAAT/增强子结合蛋白同源蛋白和切割的半胱天冬酶-12的表达。我们发现,MAPK抑制剂PD-98059显著降低心肌梗死面积、血清CK-MB和c Tn I水平;PD-98059预处理显著提高了OGD/R细胞活力的恢复和细胞凋亡的降低(p0.05)。此外,PD-98059预处理可显着降低葡萄糖调节蛋白78,CCAAT/增强子结合蛋白同源蛋白,并在m RNA水平和蛋白水平上切割caspase-12表达(p0.05)。这一研究表明,MAPK信号通路在通过抑制内质网应激调节心肌细胞凋亡中起着重要作用。
[Abstract]:The purpose of this study was to evaluate the role of MAPK signaling pathway in regulating cardiac myocyte apoptosis during post-infarction heart failure and its possible mechanism. The model of heart failure was established by left anterior descending coronary artery occlusion in mice. The myocardial infarction area, the levels of creatine kinase-MBK-MBK and cardiac troponin I were measured by histochemistry and ELISA, respectively. In addition, the direct cytotoxicity of OGD-R) to cardiomyocytes pretreated with and without MAPK inhibitor PD-98059 was evaluated. The effects of PD-98059 on cell viability, lactate dehydrogenase (LDH) release and apoptosis were measured by MTTG-ELISA and flow cytometry, respectively. RT-PCR and Western blotting were used to detect the expression of stress markers such as glucose-regulated protein 78 / enhancer binding protein homologous protein and cleavage cysteinase 12. We found that MAPK inhibitor PD-98059 significantly decreased myocardial infarction size, serum CK-MB and c Tn I levels were significantly increased by PD-98059 pretreatment, and OGD/R cell viability recovery and apoptosis decreased (P 0.05). In addition pretreatment with PD-98059 could significantly reduce the homologous protein of glucose regulated protein 78 CCAATT / enhancer binding protein and cut down the expression of caspase-12 at m RNA level and protein level. This study suggests that MAPK signaling pathway plays an important role in regulating cardiomyocyte apoptosis by inhibiting endoplasmic reticulum stress.
【作者单位】：重庆医科大学附属永川医院儿科;
【基金】：重庆医科大学附属永川医院资助
【分类号】：R54

【相似文献】