α-亚麻酸在缺血性心衰中的保护作用及其对缺血早期炎症小体NLRP3的抑制作用  

Protective effects of α-Linolenic acid against ischemic heart failure and the underlying mechanisms: inhibition of NLRP3 in the early stage of ischemia

作　　者：南瑛 赵美娜[2] 张薇 

机构地区：[1]西安医学院基础医学部生理学教研室,710021 [2]第四军医大学西京医院药剂科,西安710032 [3]唐都医院心血管内科

出　　处：《免疫学杂志》2018年第3期207-213,共7页Immunological Journal

基　　金：国家自然科学基金(81470537;31371150);陕西省教育厅专项科研计划(16JK1649);西安医学院博士科研基金启动项目(2015DOC10)

摘　　要：目的探讨α-亚麻酸(α-linolenic acid,ALA)在缺血性心衰中的保护作用及其对TNF-α、IL-6和炎症小体NLRP3(pyrin domain containing 3)等炎症介质的影响。方法通过结扎冠状动脉建立大鼠心肌梗死(myocardial infarction,MI)模型,给予ALA或其对照,监测MI后1周、2周和4周大鼠血清中TNF-α和IL-6炎症因子变化,检测MI后1周心肌组织中NLRP3相关蛋白及和MI后4周心脏功能的变化。结果与假手术组比较,血清中TNF-α和IL-6水平在MI后1周和2周均显著增加。MI后1周缺血区心肌组织中NLRP3表达显著增加,半胱氨酸蛋白酶1(cysteinyl aspartate specific protease-1,caspase-1)活性升高,IL-1β和TNF-α蛋白含量显著升高。补充ALA不仅显著降低大鼠MI后1周和2周血清中TNF-α和IL-6水平,而且减少MI后1周心肌组织中的NLRP3含量和caspase-1活性,进而降低了IL-1β和TNF-α含量,减少了中性粒细胞在心肌组织中的浸润,改善了MI 4周后的心脏功能。结论 MI前补充ALA可减少MI后1周炎症小体NLRP3相关蛋白表达,抑制TNF-α、IL-1β及IL-6炎症因子的生成,改善MI 4周后的心脏功能,延缓缺血性心衰的发生发展。α-Linolenic acid（ALA） is a kind of plant-derived polyunsaturated fatty acids（PUFAs） and has been reported to be cardioprotective by clinical studies. The aim of the present study is to investigate the protective effects of ALA against ischemic heart failure and the underlying mechanisms. The rat model of myocardial infarction（MI） was established by coronary artery ligation. Then Western blot and enzyme-linked immunosorbent assay（ELISA） were used respectively to detect NLR family, pyrin domain containing 3（NLRP3） inflammasome, TNF-αand IL-6 levels. Cardiac function was examined by a polyethylene catheter（PE-50） inserting into the left ventricular cavity through the right carotid artery. Data showed that compared with the sham MI group, serum TNF-α and IL-6 increased significantly 1 week after MI. In addition, NLRP3 expression, cysteinyl aspartate specific protease-1（caspase-1） activity, IL-1β levels and neutrophil infiltration were increased in the ischemic myocardial tissue 1 week after MI; cardiac function decreased 4 weeks after MI. Supplementary ALA significantly reduced serum TNF-α and IL-6 levels in MI rats, inhibited NLRP3 expression and caspase-1 activity, decreased IL-1β levels, thus blocked neutrophil infiltration in myocardial tissue 1 week after MI. More importantly, supplementary ALA significantly improved cardiac function 4 weeks after MI. Taken together, ALA significantly inhibits NLRP3 inflammasome,TNF-α and IL-1β and IL-6 in the early stage of MI and consequently improves cardiac function later after MI.

关 键 词：心肌梗死 Α-亚麻酸 炎症 

分 类 号：R541.4[医药卫生—心血管疾病]