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目的:我们的前期实验发现,腺病毒中介的peroxiredoxin Ⅱ(Prx Ⅱ)过表达可保护心肌细胞防止氧化应激所致的损伤,尽管这样,Prx Ⅱ在器官和整体动物水平是否具有心肌保护作用,而且这一保护作用是否通过内质网应激发挥作用尚不清楚。方法:应用Langendorff系统构建离体心肌缺血再灌注损伤模型;结扎冠状动脉左前降支,缺血30 min再灌注30 min/3 h/24 h构建体内心肌缺血再灌注损伤模型。结果:离体心肌缺血再灌后,Prx Ⅱ过表达小鼠心肌收缩最大速率(+dp/dtmax)和心肌舒张最大速率(-dp/dtmax)恢复较正常对照组明显得到改善;Prx Ⅱ心肌特异性过表达小鼠与野生型相比,离体和在体心肌缺血再灌后,心肌梗死面积均分别降低了69.13%和60.86%;体内心肌缺血再灌注,与野生型小鼠相比,Prx Ⅱ心肌特异性过表达小鼠心肌细胞凋亡率降低了52.10%±5.32%;与野生型小鼠相比,Prx Ⅱ心肌特异性过表达小鼠中内质网通路伴侣分子Hsp90、GRP94、PDI和p-e IF2α的表达量均明显降低(P<0.05),但cleaved ATF6和XBP-1的表达量在2组小鼠中无明显差异。p-Akt(Ser473)和p-Akt(Thr308)水平在野生型小鼠明显降低,在Prx Ⅱ过表达小鼠中仍维持高表达水平(P<0.05)。结论:Prx Ⅱ对缺血再灌注损伤心肌具有保护作用,其机制可能与拮抗p-e IF2α表达、增加p-Akt表达、阻断内质网应激启动的凋亡通路有关。
OBJECTIVE: Our previous study found that adenovirus-mediated peroxiredoxin II (Prx II) overexpression protects cardiomyocytes from oxidative stress-induced injury, although whether Prx II has cardioprotective effects at organ and in whole animal levels, And whether this protective effect exerts its effect through endoplasmic reticulum is unclear. Methods: Langendorff system was used to establish the model of myocardial ischemia-reperfusion injury in rats. Ligation of the left anterior descending coronary artery was performed to establish the model of myocardial ischemia-reperfusion injury after reperfusion for 30 min / 3 h / 24 h. Results: After myocardial ischemia-reperfusion in vitro, the maximum rate of myocardial contractions (+ dp / dtmax) and maximum diastolic velocity (-dp / dtmax) in Prx Ⅱ overexpression mice were significantly improved compared with the normal control group. Prx Ⅱ myocardium Compared with the wild-type mice, the area of myocardial infarction decreased by 69.13% and 60.86% respectively in vitro and in vivo after myocardial ischemia-reperfusion in mice with specific overexpression; Compared with the wild-type mice, Prx Ⅱ-specific over-expression of cardiac myocyte apoptosis-inducing factor Hsp90, The expressions of GRP94, PDI and pe IF2α were significantly decreased (P <0.05), but the expressions of cleaved ATF6 and XBP-1 were not significantly different between the two groups. The levels of p-Akt (Ser473) and p-Akt (Thr308) were significantly decreased in wild type mice and remained high in Prx Ⅱ overexpression mice (P <0.05). CONCLUSION: Prx II may have a protective effect on myocardial ischemia-reperfusion injury. Its mechanism may be related to antagonizing the expression of p-eIF2α, increasing the expression of p-Akt, and blocking the apoptosis pathway initiated by endoplasmic reticulum stress.