姜黄素通过激活Nrf2/Nox4通路调控压力负荷诱导的心力衰竭

Curcumin regulates pressure overload-induced heart failure through activating Nrf2/Nox4 signaling pathway

目的探讨姜黄素(CUR)对小鼠压力负荷性心力衰竭(HF)的保护作用及可能机制。方法 30只健康雄性C57BL/6小鼠随机分成假手术组(Sham)、心力衰竭组(HF)和姜黄素治疗组(HF+CUR)。通过主动脉弓缩窄(TAC)建立小鼠压力负荷性心力衰竭模型。实验第4周,收集各组小鼠心肌组织,称取心脏重量,计算心脏重量指数;HE染色观察心脏组织病理学改变;Western blot检测MDA5,IRE-a I、SOD-1、Nrf2和Nox4蛋白的表达。结果 HF组小鼠心脏重量和心脏重量指数显著增加,心肌间质出现明显的炎症细胞浸润,促氧化应激蛋白MDA5和IRE-a I表达升高,而SOD-1蛋白表达降低。CUR处理显著降低小鼠心脏重量和心脏重量指数,减少心肌间质炎症细胞浸润,降低MDA5和IRE-a I蛋白表达,提高SOD-1蛋白表达。此外,CUR处理还能显著增加Nrf2蛋白表达,降低Nox4蛋白表达。结论 CUR处理对小鼠压力负荷性HF有保护作用,其潜在机制可能与激活Nrf2/Nox4信号通路相关。

Objective To investigate the protective effect of curcumin(CUR) on pressure overload heart failure(HF) in mice and its possible mechanism. Methods 30 healthy male C57 BL/6 mice were randomly divided into sham operation group(sham), heart failure group(HF) and curcumin treatment group(HF+CUR). The model of pressure overload heart failure in mice was established by coarctation of aortic arch(TAC). At the fourth week of the experiment, the myocardial tissue of mice in each group was collected, the weight of the heart was weighed, and the cardiac weight index was calculated;the pathological changes of the heart were observed by HE staining;the expressions of MDA5, IRE-a I, SOD-1, Nf2 and Nox4 were detected by Western blot. Results The heart weight and heart weight index were significantly increased, inflammatory cell infiltration was observed, and the expression of MDA5 and IRE-a was increased, while the expression of SOD-1 was decreased in HF group. CUR treatment significantly decreased theheart weight and heart weight index, decreased the infiltration of inflammatory cells, decreased the expression of MDA5 and IRE-a protein, and increased the expression of SOD-1 protein. Moreover, CUR significantly increased Nrf2 protein expression, and decreased the expression of NOX4 protein. Conclusion CUR treatment has protective effect on TAC-induced HF in mice, and the underlying mechanism may be related to activation of Nrf2/Nox4 signaling pathway.