血根碱通过PI3K/AKT信号通路减轻心肌缺血再灌注损伤

Sanguinarine Ameliorates Myocardium Ischemia-Reperfusion Injury by Activating PI3K/AKT Signaling Pathway

目的探究血根碱预处理对心肌缺血再灌注损伤的保护作用及其潜在的病理生理机制。方法通过结扎左冠状动脉前降支30 min,再灌注2 h,建立大鼠心肌缺血再灌注损伤模型。在再灌注过程的起始通过尾静脉注射血根碱(50 mg·kg^(-1)),HE染色检测心肌的组织学改变,生化试剂盒检测血浆中乳酸脱氢酶(LDH)和肌酸激酶同工酶(CK-MB)的水平,ELISA试剂盒检测心肌组织中炎症因子IL-6和TNF-α的表达,Western blot检测心肌组织中PI3K、p-PI3K、AKT和p-AKT的表达水平。结果再灌注损伤后,模型组血浆中LDH和CK-MB的水平明显升高,心肌组织中IL-6和TNF-α的水平也明显增高,而p-PI3K和p-AKT蛋白水平的表达明显降低。而血根碱(50mg·kg^(-1))预处理可以显著降低再灌注损伤后血浆中LDH和CK-MB的水平,减少心肌组织中IL-6和TNF-α的水平,同时明显上调p-PI3K和p-AKT蛋白的表达。结论血根碱预处理可以减轻炎症反应,从而缓解心肌缺血再灌注损伤。

Objective To explore the protective effect of Sanguinarine preconditioning on myocardial ischemia and reperfusion injury (MIRI) and underlying pathophysiological mechanisms. Methods MIRI model was established in rats by ligating the left anterior descending (LAD) coronary artery for 30 min followed by 2 h reperfusion. Sanguinarine (50 mg · kg^(-1)) was administrated at the onset of reperfusion through tail vein. Myocardial histological examination was performed by HE staining. Plasma levels of the lactate dehydrogenase (LDH) and CK-MB were tested by commercialized assay kits. The expression of IL-6 and TNF-α in myocardial tissue were measured by ELISA Kit. The protein expression of AKT and p-AKT were evaluated by western blotting analysis. Results After reperfusion injury,the plasma levels of LDH and CK-MB in the I/R group were significantly increased,the levels of IL-6 and TNF-α in myocardial tissue were up-regulated, the protein expression of p-PI3K and p-AKT significantly decreased. However,Sanguinarine (50 mg · kg^(-1)) significantly reduced the level of LDH and CK-MB in plasma. Besides,the level of IL-6 and TNF-α in myocardial tissue were also markedly reduced. Moreover,pretreating with Sanguinarine could notably up-regulate the expression of p-PI3K and p-AKT as well. Conclusion Sanguinarine pretreatment could prominently ameliorate MIRI by activating the PI3K/AKT signaling pathway.