| 王雅男,李红杰,杨一飞,马艳霞,朱艳梅,焦凤辉,张仁杰,杨 华,李 宁,李 琴.腺苷受体激动剂对心肌缺血再灌注损伤大鼠内质网应激的影响及其作用机制研究[J].现代生物医学进展英文版,2018,(17):3245-3249. |
| 腺苷受体激动剂对心肌缺血再灌注损伤大鼠内质网应激的影响及其作用机制研究 |
| Effect and Mechanism of Adenosine Receptor Agonist on Endoplasmic Reticulum Stress in Rats with Myocardial Ischemia Reperfusion Injury |
| Received:October 23, 2017 Revised:November 19, 2017 |
| DOI：10.13241/j.cnki.pmb.2018.17.009 |
| 中文关键词: 腺苷受体激动剂 心肌缺血再灌注损伤 内质网应激 心肌梗死 |
| 英文关键词: Adenosine receptor agonist Myocardial ischemia reperfusion injury Endoplasmic reticulum stress Myocardial infarction |
| 基金项目:河北省医学科学研究计划重点项目（071050） |
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| 中文摘要: |
| 摘要 目的：探讨腺苷受体激动剂对心肌缺血再灌注损伤（MIRI）大鼠内质网应激（ERS）的影响及其作用机制。方法：选取雄性成年Wistar大鼠56只，利用Langendorff装置制成大鼠离体心脏MIRI模型。随机分为四组（n=14）：假手术组（Sham组）、心肌缺血再灌注组（MIRI组）、腺苷受体激动剂组（NECA组）和内质网应激抑制剂组(TUDCA组)。利用透射电镜观察四组心肌超微结构的变化；免疫组化观察心肌肌醇依赖酶1α（IRE1α）的表达情况；Western blot方法检测心肌ERS中IRE1-XBP1信号通路标志蛋白IRE1α、X盒结合蛋白1s（XBP1s）的表达水平；TUNEL检测心肌细胞凋亡情况。结果：透射电镜结果显示，Sham组肌丝排列规则致密，嵴排列整齐，外膜和肌节形态完整；MIRI组大部分肌丝断裂，肌节挛缩变形，嵴排列稀疏结构破坏，间隙增宽，可见线粒体空泡变性；NECA组及TUDCA组较MIRI组损伤减轻，内质网轻度扩张或者正常，肌丝排列较整齐。免疫组化结果发现，Sham组心肌纤维呈细长圆柱形，形态正常，少量结缔组织存在，基本无IRE1α阳性染色；MIRI组细胞排列紊乱，有许多断裂的细胞出现，IRE1α阳性染色区域显著增加，而NECA和TUDCA组细胞病理的变化较轻，相对于MIRI组，IRE1α阳性染色部位明显减少。Western blot结果显示，与Sham组相比，MIRI组的IRE1α和XBP1s蛋白的表达水平明显上升（P<0.05）；而与MIRI组相比，TUDCA组及NECA组IRE1α和XBP1s的蛋白表达水平显著降低（P<0.05）。TUNEL结果显示，MIRI组细胞凋亡明显，Sham组基本没有发生心肌细胞凋亡，MIRI组较NECA 组及TUDCA组的凋亡细胞数更多。结论：NECA可通过抑制IRE1-XBP1信号通路来减轻ERS反应，达到保护心肌组织细胞的目的。 |
| 英文摘要: |
| ABSTRACT Objective: To investigate the effect and mechanism of adenosine receptor agonist on endoplasmic reticulum stress (ERS) in rats with myocardial ischemia-reperfusion injury (MIRI). Methods: 56 male adult Wistar rats were selected, and the rat models of Isolated heart MIRI were established by Langendorff. The rats were randomly divided into four groups(n=14): sham operation group (Sham group), myocardial ischemia reperfusion group(MIRI group), adenosine receptor agonist group (NECA group) and endoplasmic reticulum stress inhibitor Group(TUDCA group). The ultrastructural changes of myocardium in four groups were observed by transmis- sion electron microscopy. The expression of myo inositol dependent enzyme 1α(IRE1α) was observed by immunohistochemistry. The expression of IRE1-XBP1 signal pathway marker protein IRE1α and X box binding protein 1s(XBP1s) in ERS of myocardium were de- tected by Western blot. The cardiomyocyte apoptosis was detected by TUNEL. Results: The results of transmission electron microscopy showed that the arrangement of muscle filament was regular and compact, the cristae were arranged neatly and the outer membrane and sarcomere morphological integrity in the Sham group. MIRI group showed most of the myofilament rupture, sarcomere contracture defor- mation, crista sparse structure damage, the gap widening, visible mitochondrial vacuolar degeneration. Compared with MIRI group, the injury was mild, the endoplasmic reticulum dilated slightly or normal, and the arrangement of muscle filament was neat in NECA group and TUDCA group. Immunohistochemistry showed that the Sham group showed a slender, cylindrical shape, normal morphology, and a small amount of connective tissue, and there was no IRE1α positive staining. The cell arrangement of MIRI group was disorder, and many broken cells appeared, IRE1α positive staining area increased significantly ,the pathological changes of NECA and TUDCA group were less than that of MIRI group, and the positive staining sites of IRE1α were significantly decreased. The expression levels of IRE1α and XBP1s protein in MIRI group were significantly increased compared with Sham group by Western blot (P<0.05), the protein expres- sion levels of IRE1α and XBP1s in TUDCA group and NECA group were significantly decreased when compared with the MIRI group (P<0.05). The results of TUNEL showed that there was obvious apoptosis in the MIRI group, but there was no apoptosis in the Sham group, the apoptotic cells in the MIRI group were higher than those in the NECA group and the TUDCA group. Conclusion: NECA can alleviate the ERS response by inhibiting the IRE1-XBP1 signaling pathway and protect the cardiac muscle tissue cells. |
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