本文選題：MAPK信號通路 + 心肌細胞凋亡��； 參考：《基因組學與應用生物學》2017年08期

【摘要】：本研究旨在評估MAPK信號通路在梗死后心力衰竭期間調(diào)節(jié)心肌細胞凋亡中的作用及其可能的潛在機制。通過左前降支冠狀動脈閉塞誘發(fā)構(gòu)建梗死后心力衰竭的小鼠模型,通過組織化學和ELISA分別測定血清中心肌梗死面積和肌酸激酶-MB(CK-MB)和心肌肌鈣蛋白(c Tn I)水平。此外,評估了氧-葡萄糖剝奪/恢復(OGD/R)對具有和不具有MAPK抑制劑PD-98059預處理的心肌細胞的直接細胞毒性作用。分別采用MTT、ELISA和流式細胞術(shù)測定PD-98059對細胞活力、乳酸脫氫酶(LDH)釋放和細胞凋亡的影響。采用RT-PCR和Western blotting檢測內(nèi)質(zhì)網(wǎng)(ER)應激標志物如葡萄糖調(diào)節(jié)蛋白78、CCAAT/增強子結(jié)合蛋白同源蛋白和切割的半胱天冬酶-12的表達。我們發(fā)現(xiàn),MAPK抑制劑PD-98059顯著降低心肌梗死面積、血清CK-MB和c Tn I水平;PD-98059預處理顯著提高了OGD/R細胞活力的恢復和細胞凋亡的降低(p0.05)。此外,PD-98059預處理可顯著降低葡萄糖調(diào)節(jié)蛋白78,CCAAT/增強子結(jié)合蛋白同源蛋白,并在m RNA水平和蛋白水平上切割caspase-12表達(p0.05)。這一研究表明,MAPK信號通路在通過抑制內(nèi)質(zhì)網(wǎng)應激調(diào)節(jié)心肌細胞凋亡中起著重要作用。
[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.
【作者單位】： 重慶醫(yī)科大學附屬永川醫(yī)院兒科;
【基金】：重慶醫(yī)科大學附屬永川醫(yī)院資助
【分類號】：R54

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