摘要
目的探究姜黄素能否通过增强自噬活性改善自身免疫性心肌炎(experimental autoimmune myocarditis,EAM)大鼠心功能。方法以6周龄Lewis大鼠为研究对象,建立EAM模型,随机分为模型组(EAM)、姜黄素处理组(Cur),并另设对照组(Con)(每组7只)。玉米油或姜黄素灌胃干预21 d后,心动超声检测并评价大鼠心功能各项指标的变化;Western blot法检测微管相关蛋白轻链3(microtubule-associated protein light chain 3,LC3)表达;Real-time PCR法检测大鼠心肌微管相关蛋白LC3上游基因Beclin-1及ATG-5的mRNA表达。结果心脏超声提示,与对照组相比,EAM组大鼠心率增快(P<0.001),左室收缩末内径(left ventricular end-systolic diameter,LVEDs)扩大(P=0.018),射血分数(ejection fraction,EF)下降(P<0.001),差异均有统计学意义(P<0.05);姜黄素干预后,大鼠心率减慢(P<0.001),LVEDs变小(P=0.030),EF改善(P<0.001);EAM组大鼠心肌组织LC3的表达高于Con组( P= 0.026),而给予姜黄素处理后,LC3表达较EAM组进一步升高( P= 0.014);EAM组中LC3上游因子Beclin-1表达较Con组明显升高,且差异有统计学意义( P= 0.041),姜黄素处理后,Beclin-1表达升高更加显著( P= 0.003);ATG-5虽在EAM组及Cur组表达有增高趋势,然而差异并无统计学意义( P= 0.108)。结论姜黄素能够通过促进心肌炎大鼠心肌自噬活性从而改善EAM大鼠心脏功能,该作用通过促进Beclin-1的表达而实现。
Objective To explore whether curcumin can improve cardiac function in rats with experimental autoimmune myocarditis (EAM) by enhancing myocardial autophagy activity. Methods We used 6-week-old Lewis rats to establish a model of autoimmune myocarditis by the classical method of porcine myocardium immunoglobulin. We randomly divided 21 rats into three groups: control group (Con),autoimmune myocarditis group (EAM),and curcumin-treated group (Cur),with 7 in each group. The rats were treated with curcumin for 21 days. The structure and function of rat heart was evaluated by echocardiography on day 22. Western blot was used to detect the expression of microtubule-associated protein light chain 3 (LC3). The expressions of Beclin-1 and ATG-5 in the myocardium were measured by Real-time PCR. Results The echocardiography showed that left ventricular systolic function was abnormal in EAM rats compared with rats in Con group. After administration of curcumin,rats in Cur group had better left ventricular systolic function than EAM rats. Compared with that in Con group,LC3 expression in EAM group was significantly increased ( P =0.026). After curcumin administration,the expression of LC3 increased more obviously than that in EAM group ( P =0.014). Beclin-1,an upstream factor of LC3,was significantly increased in EAM group ( P =0.041) and increased even higher under administration of curcumin ( P =0.003). ATG-5,another LC3 upstream factor,did not significantly differ among the three groups ( P =0.108). Conclusion Curcumin can improve cardiac function in rats with autoimmune myocarditis by inducing myocardial autophagy activity,which is mediated through the promotion of Beclin-1.
作者
郜珊珊
霍建华
王晨
邓伏雪
王丽君
强华
GAO Shan-shan;HUO Jian-hua;WANG Chen;DENG Fu-xue;WANG Li-jun;QIANG Hua(Department of Cardiology,The First Affiliated Hospital of Xi'an Jiaotong University,Xi'an 710061;Key Laboratory of Molecular Cardiology,Xi'an Jiaotong University,Xi'an 710061;Key Laboratory of Environment and Genes Related to Diseases,Xi'an Jiaotong University Ministry of Education,Xi'an 710061,China)
出处
《西安交通大学学报（医学版）》
CAS
CSCD
北大核心
2019年第6期1018-1022,共5页
Journal of Xi’an Jiaotong University（Medical Sciences）
基金
国家自然科学基金青年基金资助项目(No.81700447
No.81500389)
陕西省自然科学基金资助项目(No.2018JM7106,No.2019JQ-955)
西安交通大学第一附属医院临床研究基金资助项目(XJTU1AF-CRF-2018-010)~~
关键词
姜黄素
自身免疫性心肌炎
自噬
curcumin
experimental autoimmune myocarditis
autophagy
