Department of Cardiology, The First Affiliated Hospital of Guangxi Medical University & Guangxi Key Laboratory Base of Precision Medicine in Cardio-Cerebrovascular Diseases Control and Prevention & Guangxi Clinical Research Center for Cardio-Cerebrovascular Diseases, Nanning, People's Republic of China.
Drug Des Devel Ther. 2021 Sep 7;15:3821-3834. doi: 10.2147/DDDT.S323555. eCollection 2021.
Coronary microembolization (CME) is associated with progressive cardiac dysfunction, myocardial inflammation, and apoptosis. Resveratrol (RES) has a considerable role in cardioprotection. However, the contribution and possible mechanisms of RES in CME have not been clearly understood.
In the current study, 40 SD rats were randomly selected and categorized into various groups including CME, CME + resveratrol (CME + RES), CME + resveratrol+ LY294002 (CME + RES + LY), and sham groups (10 animals in each group). The inert plastic microspheres (42 μm) were injected into the rats' left ventricle for developing the CME model. Then resveratrol (25 mg/kg/d) was given to the rats in the CME + RES and CME + RES + LY groups for one week before CME induction. Furthermore, LY294002 (10 mg/kg) was intraperitoneally injected into the rats of the CME + RES + LY group 0.5 hours before CME modeling. The cardiac functions, serum levels of myocardial injury biomarkers, myocardial histopathology, and mRNA and proteins associated with myocardial apoptosis were all assessed 12 hours after surgery.
The results revealed that resveratrol pretreatment alleviated the CME-induced myocardial damage by improving cardiac dysfunction, and lowering the serum level of myocardial injury biomarkers, myocardial microinfarct size, and cardiomyocyte apoptotic index. Pretreatment with resveratrol reduced the level of proteins and mRNAs associated with the pro-apoptosis in myocardial tissues and increased the levels of proteins and mRNAs associated with the anti-apoptosis. Moreover, the combined treatment of resveratrol and LY294002 reversed the observed protective effects.
Resveratrol can inhibit cardiomyocyte apoptosis, thus attenuating the CME-induced myocardial injury by triggering the PI3K/Akt/GSK-3β cascade.
冠状动脉微栓塞（CME）与进行性心功能障碍、心肌炎症和细胞凋亡有关。白藜芦醇（RES）在心保护中具有重要作用。然而，RES 在 CME 中的作用和可能的机制尚不清楚。
本研究中，将 40 只 SD 大鼠随机分为 CME 组、CME+白藜芦醇（CME+RES）组、CME+白藜芦醇+LY294002（CME+RES+LY）组和假手术组（每组 10 只）。将惰性塑料微球（42μm）注入大鼠左心室以建立 CME 模型。然后，在 CME 诱导前一周，给予 CME+RES 和 CME+RES+LY 组大鼠 RES（25mg/kg/d）。此外，在 CME 建模前 0.5 小时，CME+RES+LY 组大鼠腹腔内注射 LY294002（10mg/kg）。手术后 12 小时评估心脏功能、血清心肌损伤标志物水平、心肌组织病理学以及与心肌细胞凋亡相关的 mRNA 和蛋白。
RES 预处理通过改善心功能障碍、降低血清心肌损伤标志物水平、心肌微梗死面积和心肌细胞凋亡指数，减轻 CME 诱导的心肌损伤。RES 预处理降低了心肌组织中与促凋亡相关的蛋白和 mRNAs 水平，增加了与抗凋亡相关的蛋白和 mRNAs 水平。此外，RES 和 LY294002 的联合治疗逆转了观察到的保护作用。
RES 可抑制心肌细胞凋亡，通过激活 PI3K/Akt/GSK-3β 级联反应，减轻 CME 诱导的心肌损伤。
