NECA抑制内质网应激抗大鼠心肌缺血再灌注损伤的作用机制
发布时间:2018-05-09 15:56
本文选题:NECA + 心肌缺血再灌注损伤 ; 参考:《医学研究生学报》2017年06期
【摘要】:目的腺苷受体激动剂NECA具有一定的心肌保护作用,但具体机制尚不明确。文中探讨NECA对大鼠心肌缺血再灌注损伤内质网应激的作用及机制。方法选取SPF级雄性成年Wistar大鼠56只,利用Langendorff装置制成大鼠离体心脏缺血再灌注损伤模型。随机数字表法分为假手术组、缺血再灌注组、腺苷受体激动剂组和内质网应激抑制剂组,每组14只。假手术组:心脏穿线但不结扎,用Kerbs-Henseleit缓冲液持续灌流170 min;缺血再灌注组:心脏稳定20 min,缺血30min,再灌注2 h;腺苷受体激动剂组、内质网应激组:心脏稳定20 min,缺血30 min,再灌注2 h,于再灌注前5 min分别给予含0.1μmol/L NECA的灌流液、30μmol/L TUDCA的灌流液,均至再灌注30 min时结束。透射电镜观察心肌超微结构的变化;Western blot方法检测内质网应激IREl-XBPl信号通路标志蛋白IRE1α、XBP1s的表达水平;免疫组化观察IRE1α的表达情况。结果透射电镜结果显示,缺血再灌注组大部分肌丝断裂,肌节挛缩变形,可见线粒体空泡变性;腺苷受体激动剂组及内质网应激组较缺血再灌注组损伤减轻,表现为肌丝排列较整齐,肌节仅有轻度挛缩。免疫组化结果发现,假手术组基本无IRE1α阳性染色,缺血再灌注组IRE1α阳性染色区域显著增加,而NECA和内质网应激抑制剂组IRE1α阳性染色部位明显减少。与假手术组相比,缺血再灌注组的IRE1α和XBP1s蛋白的表达水平明显上升(P0.05);而与缺血再灌注组IRE1α和XBP1s的蛋白表达水平(1.72±0.27、0.97±0.19)相比,腺苷受体激动剂组(1.14±0.16、0.60±0.13)及内质网应激抑制剂组(1.07±0.27、0.58±0.15)显著降低(P0.05)。结论 NECA可通过抑制IREl-XBPl信号通路来减轻内质网应激,从而发挥心肌保护作用。
[Abstract]:Objective adenosine receptor agonist (NECA) has a protective effect on myocardium, but the mechanism is unclear. To investigate the effect and mechanism of NECA on endoplasmic reticulum stress during myocardial ischemia reperfusion injury in rats. Methods Fifty-six adult SPF male Wistar rats were selected and the model of isolated heart ischemia-reperfusion injury was established by Langendorff device. The rats were randomly divided into sham-operated group, ischemia-reperfusion group, adenosine receptor agonist group and endoplasmic reticulum stress inhibitor group with 14 rats in each group. Sham operation group: the heart pierced but not ligated, perfused continuously with Kerbs-Henseleit buffer for 170min; Ischemia-reperfusion group: cardiac stability 20 min, ischemia 30 min, reperfusion 2 h; adenosine receptor agonist group, adenosine receptor agonist group, In the endoplasmic reticulum stress group, the heart was stable for 20 minutes, ischemia for 30 minutes, reperfusion for 2 hours, and perfused with 0.1 渭 mol/L NECA of 30 渭 mol/L TUDCA at 5 min before reperfusion until 30 min after reperfusion. The changes of myocardial ultrastructure were observed by transmission electron microscope. The expression of IRE1 伪 XBP1s, a marker of IREl-XBPl signaling pathway in endoplasmic reticulum stress, and the expression of IRE1 伪 were detected by Western blot. Results the results of transmission electron microscope showed that most of the myofilms were broken and the sarcomere contracture was deformed in the ischemia-reperfusion group, the vacuolar degeneration of mitochondria was observed, the damage of adenosine receptor agonist group and endoplasmic reticulum stress group was less than that of the ischemia reperfusion group. The myofilaments were arranged neatly, and the sarcomere was only slightly contracture. The immunohistochemical results showed that there was no IRE1 伪 positive staining in sham-operated group, but the area of IRE1 伪 positive staining in ischemia-reperfusion group was significantly increased, while that in NECA and endoplasmic reticulum stress inhibitor group was significantly decreased. Compared with sham operation group, the expression level of IRE1 伪 and XBP1s protein in ischemia reperfusion group was significantly higher than that in ischemia reperfusion group, but the protein expression level of IRE1 伪 and XBP1s in ischemia reperfusion group was 1.72 卤0.270.97 卤0.19), the expression level of IRE1 伪 and XBP1s in adenosine receptor agonist group was 1.14 卤0.160.60 卤0.13) and that in endoplasmic reticulum stress inhibitor group (1.07 卤0.270.58 卤0.15) was significantly lower than that in ischemia-reperfusion group (1.72 卤0.270.97 卤0.19), and that in endoplasmic reticulum stress inhibitor group (1.07 卤0.270.58 卤0.15) was significantly lower than that in sham operation group. Conclusion NECA can attenuate endoplasmic reticulum stress by inhibiting IREl-XBPl signaling pathway, thus exerting myocardial protection.
【作者单位】: 华北理工大学护理与康复学院;
【基金】:河北省人才工程培养经费资助[冀人社字(2012)334] 河北省科技厅基金项目(16277787D)
【分类号】:R54
【相似文献】
相关硕士学位论文 前1条
1 赵萌;NECA诱导抗心肌/缺血再灌注损伤保护作用的线粒体机制研究[D];天津医科大学;2015年
,本文编号:1866631
本文链接:https://www.wllwen.com/yixuelunwen/xxg/1866631.html
最近更新
教材专著