白藜芦醇通过调节沉默信息调节因子1/核转录因子-κB通路改善高血压左心室重塑  

Resveratrol ameliorates hypertensive left ventricular remodeling by regulating the silent information regulator 1/nuclear transcription factor-κB pathway

作　　者：黄健 范忠才 程圣杰 Huang Jian;Fan Zhongcai;Cheng Shengjie(Department of Cardiology,Affiliated Hospital of Southwest Medical University)

机构地区：[1]西南医科大学附属医院心血管内科,泸州646000

出　　处：《重庆医科大学学报》2021年第12期1440-1447,共8页Journal of Chongqing Medical University

基　　金：西南医科大学-四川省心血管疾病防治协同创新中心资助项目(编号:xtcx-2016-23)。

摘　　要：目的:研究白藜芦醇(resveratrol,RES)对自发性高血压大鼠(spontaneous hypertension rat,SHR)左心室重塑的影响及其对沉默信息调节因子1(silent information regulator 1,SIRT1)/核转录因子κB(nuclear transcription factor-κB,NF-κB)信号通路的作用。方法:将8只8周龄雄性Wistar-Kyoto(WKY)大鼠作为正常组(WKY组),将40只8周龄雄性SHR随机分为SHR组、RES组、EX527组、RES+EX527组、RES+吡咯烷二硫代氨基甲酸盐(pyrrolidine dithiocarbamate,PDTC)组,每组8只,予以相应药物干预12周。测量大鼠体质量、收缩压、心脏超声、左心室质量、左心室质量指数(left ventricular mass index,LVMI)、心肌胶原容积分数(collagen volume fraction,CVF)、氧化应激指标、SIRT1和NF-κB以及炎症因子蛋白表达水平,观察HE和Masson染色下的心脏形态病理改变。结果:与WKY组[LVMI(2.12±0.10) mg/g,CVF(0.18±0.09)%,SIRT1蛋白表达量1.40±0.05,NF-κB蛋白表达量0.46±0.06]相比,SHR组[LVMI(3.07±0.07) mg/g,CVF(2.60±0.56)%,SIRT1蛋白表达量0.78±0.08,NF-κB蛋白表达量1.41±0.08]左心室重塑程度严重,氧化应激和炎症因子水平及NF-κB表达明显增加(P<0.05),而SIRT1表达降低(P<0.05)。RES组[LVMI(2.72±0.09) mg/g,CVF(1.10±0.30)%,SIRT1蛋白表达量0.99±0.07,NF-κB蛋白表达量0.98±0.12]较SHR组左心室重塑程度减轻,氧化应激和炎症因子水平及NF-κB表达降低(P<0.05),SIRT1表达增加(P<0.05);而EX527组[LVMI(3.18±0.08) mg/g,CVF(2.83±0.98)%,SIRT1蛋白表达量0.60±0.02,NF-κB蛋白表达量1.68±0.07]结果与RES组相反。与RES组相比,RES+EX527组有逆转RES改善左心室重塑的趋势;而RES+PDTC组更有改善左心室重塑的趋势。结论:RES能改善SHR的左心室重塑,其机制可能与调节SIRT1/NF-κB通路从而减轻氧化应激和炎症反应损伤有关。Objective:To study the effect of resveratrol(RES) on left ventricular remodeling in spontaneous hypertension rat(SHR) and its role in silent information regulator 1/nuclear transcription factor-κB(SIRT1/NF-κB) signaling pathway. Methods:Eight male Wistar-Kyoto(WKY) rats aged 8 weeks were taken as the normal group(WKY group),and 40 male SHR aged 8 weeks were randomly divided into SHR group,RES group,EX527 group,RES+EX527 group,and RES+pyrrolidine dithiocarbamate(PDTC) group,with 8 rats in each group,given corresponding drug intervention for 12 weeks. The rats’ weight,systolic pressure,echocardiography,left ventricular mass,left ventricular mass index(LVMI),myocardial collagen volume fraction(CVF),oxidative stress index,SIRT1 and NF-κB protein expression levels,and inflammatory factors protein expression levels were measured. And the morphological and pathological changes of the heart under HE and Masson staining were observed. Results:Compared with WKY group[LVMI(2.12±0.10) mg/g,CVF(0.18±0.09)%,SIRT1 protein expression(1.40±0.05),NF-κB protein expression(0.46±0.06)],SHR group[LVMI(3.07±0.07) mg/g,CVF(2.60±0.56)%,SIRT1 protein expression(0.78±0.08),NF-κB protein expression(1.41±0.08)] showed severe left ventricular remodeling,significantly increased levels of oxidative stress and inflammatory factors as well as NF-κB expression(P<0.05),and decreased SIRT1 expression(P<0.05).In RES group [LVMI(2.72 ±0.09) mg/g,CVF(1.10 ±0.30)%,SIRT1 protein expression(0.99±0.07),NF-κB protein expression(0.98 ±0.12)],compared with SHR group,left ventricular remodeling degree was reduced,oxidative stress and inflammatory factors as well as NF-κB expression levels were decreased(P<0.05),and SIRT1 expression was increased(P<0.05). The results of EX527 group [LVMI(3.18±0.08) mg/g,CVF(2.83±0.98)%,SIRT1 protein expression(0.60±0.02),NF-κB protein expression(1.68±0.07)] were opposite to those of RES group. Compared with RES group,RES + EX527 group showed a trend of reversing RES to ameliorate left ventricular remo

关 键 词：白藜芦醇 左心室重塑 沉默信息调节因子1 核转录因子ΚB 自发性高血压大鼠 

分 类 号：R541.3[医药卫生—心血管疾病]