沉默信息调节因子在姜黄素减轻炎症反应改善压力性心肌肥厚中的作用  

Curcumin alleviates cardiac hypertrophy via inhibiting inflammatory response by activating SIRT1

作　　者：熊凤梅[1] 刘瑞萍[2] 郭焕利[1] 武冬梅[1] 孙娜[3] Xiong Fengmei;Liu Ruiping;Guo Huanli;Wu Dongmei;Sun Na(Department of Pharmacy,Xi'an Children's Hospital,Xi'an 710003,China;Institute of Basic Medical Science,Xi'an Medical University,Xi'an 710021,China)

机构地区：[1]西安市儿童医院药剂科,西安710003 [2]西安市儿童医院营养科,西安710003 [3]西安医学院基础部,西安710003

出　　处：《中国体外循环杂志》2022年第2期107-112,128,共7页Chinese Journal of Extracorporeal Circulation

基　　金：西安市儿童医院院级课题(2020C01)。

摘　　要：目的 探讨姜黄素(Cur)减轻小鼠主动脉弓缩窄所致的心肌肥厚的作用以及对沉默信息调节因子(SIR)T1信号的调控。方法 通过主动脉弓缩窄术(TAC)造成心脏后负荷压力增大,诱导心肌肥厚模型,C57/BL6小鼠共48只随机分为4组(每组12只):假手术组(Sham)、TAC模型组(TAC)、Cur联合TAC组(TAC+Cur)以及Cur和SIRT1抑制剂EX527共处理TAC组(TAC+Cur+EX527)。以小鼠心脏重/体重比、心肌细胞横截面积、纤维化程度以及心肌组织中心房利钠肽(ANP)和脑钠肽(BNP)的表达作为心肌肥厚程度的评价指标;以左室射血分数(LVEF)和短轴缩短率(LVFS)评价心脏功能;免疫印迹检测心肌组织中炎症相关因子肿瘤坏死因子(TNF)-α、白介素(IL)-1β和IL-6以及心肌中SIRT1和乙酰化转录因子(FOXO1)(Ac-FOXO1)的表达。结果 和Sham组相比,TAC组心脏重量/体重比值、心肌细胞横截面积、纤维化程度以及ANP和BNP的表达均明显增加,同时LVEF和LVFS值明显降低;心肌中TNF-α、IL-1β和IL-6的表达显著增加;心肌中SIRT1的表达明显降低、Ac-FOXO1的表达明显增加;而TAC+Cur组可显著降低心脏重量/体重比值、心肌细胞横截面积、纤维化程度以及ANP和BNP的表达,并增加LVEF和LVFS值、降低TNF-α、IL-1β和IL-6的表达,同时上调SIRT1的表达,并下调Ac-FOXO1表达;而EX527能阻断Cur对TAC的这些作用。结论 Cur能够减轻小鼠压力负荷引起的心肌肥厚,其作用机制与降低炎症反应和激活SIRT1信号有关。Objective To investigate the effect of curcumin(Cur)on pressure overload-induced cardiac hypertrophy in mice and determine the role of SIRT1 signaling.Methods Cardiac hypertrophy model using minimally invasive transverse aortic constriction(TAC)surgery was generated.Forty-eight C57/BL6 mice were randomly divided into 4 groups(n=12):the sham group(Sham),the TAC group(TAC),Cur combined with TAC group(TAC+Cur),as well as Cur and the SIRT1 inhibitor EX527 co-treatment with TAC group(TAC+Cur+EX527).The heart weight/body weight ratio,myocardial cell cross-sectional area,fibrosis and the expressions of ANP and BNP in myocardial tissue were the biomarkers of cardiac hypertrophy.Cardiac function including left ventricular ejection fraction(LVEF)and left ventricular fractional shortening(LVFS)were measured by echocardiography.The protein expressions of TNF-α,IL-1β,IL-6,SIRT1 and acetylated FOXO1(Ac-FOXO1)were determined by western blot.Results Compared with the sham group,the heart weight/body weight ratio,myocardial cell cross-sectional area,fibrosis,and the expressions of ANP and BNP were significantly increased in the TAC group,while LVEF and LVFS values were notably decreased.In addition,the expressions of TNF-α,IL-1β,and IL-6 were markedly elevated in the TAC group.Moreover,the expression of SIRT1 was significantly decreased and the expression of Ac-FOXO1 was remarkably increased in the TAC group.As expected,the heart weight/body weight ratio,myocardial cross-sectional area,fibrosis,the expressions of ANP and BNP were decreased while LVEF and LVFS values were increased in the TAC+Cur group.The protein expressions of TNF-α,IL-1β,and IL-6 were also decreased in the TAC+Cur group.Meanwhile,the expression of SIRT1 was up-regulated,while the expression of Ac-FOXO1 was down-regulated.However,EX527 could block these protective effects of Cur.Conclusion Cur could reduce pressure overload-induced cardiac hypertrophy by inflammatory inhibition and SIRT1 signaling activation.

关 键 词：姜黄素 心肌肥厚 沉默信息调节因子 炎症反应 主动脉弓缩窄 小鼠 

分 类 号：R285.5[医药卫生—中药学]