NLRP3/IL-1β/TGF-β1信号轴在AngⅡ诱导高血压心肌纤维化小鼠中的作用研究  

Effect of NLRP3/IL-1β/TGF-β1 signal axis on angiotensin Ⅱ-induced hypertensive myocardial fibrosis in mice

作　　者：刘孟楠 杨廷富 罗钢 刘颜 杨思进 Liu Mengnan;Yang Tingfu;Luo Gang;Liu Yan;Yang Sijin(Department of Cardiovascular Medicine,Hospital of Traditional Chinese Medicine,Southwest Medical University,Luzhou 646000,China;不详)

机构地区：[1]西南医科大学附属中医医院心血管内科,泸州646000 [2]澳门科技大学中医药学院,中国澳门999078

出　　处：《中国循证心血管医学杂志》2022年第11期1320-1324,共5页Chinese Journal of Evidence-Based Cardiovascular Medicine

基　　金：国家自然科学基金面上项目(82074378);四川省中医药管理局项目(2021MS097);西南医科大学青年项目(2021ZKQN143);广东省中医药局面上项目(20221354);深圳市自然科学基金面上项目(JCYJ20210324111213038);广东省自然科学基金面上项目(2022A1515011647)。

摘　　要：目的探讨NLRP3/IL-1β/TGF-β1信号轴在血管紧张素Ⅱ(AngⅡ)诱导高血压心肌纤维化小鼠中的作用。方法30只雄性C57BL/6J小鼠随机分为对照组、模型组和福辛普利组。建立高血压心肌纤维化模型后,福辛普利组予以福辛普利钠1.2mg/kg·d灌胃。造模后每周检测收缩压1次;采用超声心动图检测各组小鼠心脏功能指标,包括左室舒张末期内径(LVEDd)、左室收缩末期内径(LVESd)、左心室射血分数(LVEF)和左心室缩短分数(LVFS);采用HE染色和马松染色检测小鼠心肌组织病变情况;采用RT-PCR法测定小鼠心脏NLRP3、IL-1β及TGF-β1 mRNA的表达情况;Western blot法测定小鼠心脏NLRP3、Caspase-1、IL-1β及TGF-β1蛋白的表达情况。结果模型组较对照组收缩压明显升高(P<0.05),与模型组比较,福辛普利组收缩压明显降低(P<0.05);HE及马松染色显示,对照组小鼠心肌间心肌细胞结构形态正常,排列整齐,心肌间质间几乎无蓝色胶原纤维分布,心血管形态正常;模型组小鼠心肌细胞肥大、排列紊乱,部分细胞肿胀变形、溶解,心肌间质及血管周围可见大量蓝色胶原纤维,福辛普利组可见小鼠心肌细胞排列紊乱明显改善,心肌间质蓝染的胶原纤维显著减少,心肌及血管周围的纤维化损伤均得到有效改善。RT-PCR结果显示模型组较对照组NLRP3,IL-1β及TGF-β1 mRNA表达均显著上升(P<0.01),与模型组比较,福辛普利组以上指标均显著下降(P<0.01);与对照组比较,模型组NLRP3、Caspase-1、IL-1β及TGF-β1蛋白表达均显著上升(P<0.01),与模型组比较,福辛普利组NLRP3、Caspase-1、IL-1β及TGF-β1均显著下降(P<0.05)。结论NLRP3/IL-1β/TGF-β1信号轴与高血压心肌纤维化密切相关,血管紧张素转化酶抑制剂(ACEI)类药物可控制血压并减轻心肌纤维化。Objective To study the effect of NOD-like receptor thermal protein domain associated protein 3/interleukin-1β/transforming growth factorβ1(NLRP3/IL-1β/TGF-β1)signal axis on angiotensin Ⅱ(AngⅡ)-induced hypertensive myocardial fibrosis in mice.Methods Male C57BL/6J mice(n=30)were randomly divided into control group,model group and fosinopril group.After established the model of hypertensive myocardial fibrosis,fosinopril group was orally given fosinopril(1.2mg/kg/day).The level of systolic blood pressure(SBP)was detected once a week in all groups after modeling.The indexes of heart function were detected by using echocardiogram,including left ventricular end-diastolic inner diameter(LVEDd),left ventricular end-systolic diameter(LVESd),left ventricular ejection fraction(LVEF)and left ventricular fraction shortening(LVFS).The lesions of myocardial tissue were detected by using HE staining and Masson staining.The mRNA expressions of NLRP3,IL-1β and TGF-β1 were detected by using RT-PCR.The protein expressions of NLRP3,Caspase-1,IL-1β and TGF-β1 were detected by using Western blotting assay.Results SBP increased significantly in model group compared with control group(P<0.05),and decreased significantly in fosinopril group compared with model group(P<0.05).The results of HE staining and Masson staining showed that the structure and morphology of cardiomyocytes were normal,arranged neatly,there was less blue collagen fiber distribution,and cardiovascular morphology was normal in control group,cardiomyocytes were hypertrophy and disordered,some cardiomyocytes were swollen,deformed and dissolved,and there were a lot of blue collagen fibers in myocardial interstitium and around blood vessels in model group,and disorder of cardiomyocyte was significantly relieved,stained collagen fibers were significantly reduced,and fibrotic damages around myocardium and blood vessels were effectively ameliorated in fosinopril group.The results of RT-PCR showed that the mRNA expressions of NLRP3,IL-1β and TGF-β1 increased sign

关 键 词：NLRP3 白介素-1Β 转化生长因子-β 高血压心肌纤维化 血管紧张素转化酶抑制剂 小鼠 

分 类 号：R541.3[医药卫生—心血管疾病]