槲皮素通过调节SIRT1/NF-κB通路抑制压力超负荷大鼠左心室肥厚  

Quercetin inhibits left ventricular hypertrophy in pressure-overload rats by regulating the SIRT1/NF-кB pathway

作　　者：杨荣培 刘增长[1] Yang Rongpei;Liu Zengzhang(Department of Cardiology,The Second Affiliated Hospital of Chongqing Medical University)

机构地区：[1]重庆医科大学附属第二医院心血管内科,重庆400010

出　　处：《重庆医科大学学报》2020年第4期429-435,共7页Journal of Chongqing Medical University

基　　金：国家自然科学基金青年科学基金资助项目(编号:81400004)。

摘　　要：目的:通过动物实验探讨槲皮素对压力超负荷大鼠左心室肥厚的保护作用及其可能机制。方法:通过腹主动脉缩窄手术(abdominal aorta stenosis,AAC)构造大鼠左心室肥厚模型。将造模的40只SD大鼠随机分为假手术组(Sham组)、AAC组、槲皮素组(Quercetin组)、EX527组,每组10只。Sham组、AAC组每日给予生理盐水灌胃和腹腔注射治疗;Quercetin组给予槲皮素50 mg/(kg·d)进行灌胃和生理盐水腹腔注射治疗;EX527组给予SIRT1特异性抑制剂EX527 5 mg/(kg·d)腹腔注射和槲皮素50 mg/(kg·d)灌胃治疗。4周后,计算心脏质量参数;超声心动图检测心脏功能、左心室后壁厚度;Masson染色检测心肌纤维化程度;免疫组织化学染色和蛋白质印迹法检测I型胶原(collagen typeⅠ,ColⅠ)、Ⅲ型胶原(collagenⅢ,ColⅢ)、沉默信息调节因子1(silent information regulator 1,SIRT1)、核因子-κB(nuclear factor-κB,NF-κB)的蛋白表达。结果:槲皮素可增强SIRT1的蛋白表达(Sham组:1.000±0.000,AAC组:0.364±0.071,Quercetin组:1.138±0.070,EX527组:0.293±0.092,F=240.539,P=0.000),降低心脏质量(Sham组:1.139±0.053,AAC组:1.300±0.056,Quercetin组:0.998±0.085,EX527组:0.924±0.054,F=47.296,P=0.000)、左室后壁厚度(Sham组:1.587±0.136,AAC组:2.657±0.355,Quercetin组:1.800±0.200,EX527组:2.700±0.306,F=37.304,P=0.001)和心肌纤维化程度(Sham组:8.515±1.343,AAC组;23.832±1.095,Quercetin组:13.260±0.674,EX527组:24.162±1.312,F=278.741,P=0.000),降低ColⅠ(Sham组:1.000±0.000,AAC组:3.132±0.372,Quercetin组:1.556±0.164,EX527组:2.819±0.368,F=82.083,P=0.000)、ColⅢ(Sham组:1.000±0.000,AAC组;2.395±0.437,Quercetin组:1.583±0.287,EX527组:2.434±0.461,F=23.608,P=0.024)、NF-κB(Sham组:1.000±0.000,AAC组:5.498±0.642,Quercetin组:3.637±0.715,EX527组:5.125±0.682,F=79.912,P=0.005)蛋白的表达;EX527的使用降低了SIRT1蛋白的表达(P=0.000),增加了心脏质量(P=0.001)、左室后壁厚度(P=0.000)和心肌纤维化程度(P=0.000),增加了CoObjective:To investigate the protective effect of quercetin against left ventricular hypertrophy in overload-pressure rats and possible mechanism through an animal experiment. Methods:Abdominal aorta coarctation(AAC)was performed to establish a rat model of left ventricular hypertrophy. After modeling,40 Sprague-Dawley rats were randomly divided into sham-operation group,AAC group,quercetin group,and EX527 group,with 10 rats in each group. The rats in the sham-operation group and the AAC group were given normal saline by gavage and intraperitoneal injection every day,those in the quercetin group were given 50 mg/(kg·d)quercetin by gavage and intraperitoneal injection of normal saline every day,and those in the EX527 group were given intraperitoneal injection of 5 mg/(kg·d)EX527,an SIRT1 specific inhibitor,and 50 mg/(kg·d) quercetin by gavage every day. After 4 weeks of intervention,heart mass index was calculated;echocardiography was performed to evaluate cardiac function and left ventricular posterior wall thickness;Masson staining was performed to observe the degree of myocardial fibrosis;immunohistochemical staining and Western blot were used to measure the protein expression of collagen type Ⅰ(ColⅠ),collagen Ⅲ(ColⅢ),silent information regulator 1(SIRT1),and nuclear factor-κB(NF-κB). Results:Quercetin increased the protein expression of SIRT1(1.000±0.000 in the sham-operation group,0.364±0.071 in the AAC group,1.138±0.070 in the quercetin group,and 0.293±0.092 in the EX527 group;F=240.539,P=0.000)and reduced heart mass(1.139±0.053 in the sham-operation group,1.300±0.056 in the AAC group,0.998±0.085 in the quercetin group,and 0.924±0.054 in the EX527 group;F=47.296,P=0.000),left ventricular posterior wall thickness(1.587±0.136 in the sham-operation group,2.657±0.355 in the AAC group,1.800±0.200 in the quercetin group,and2.700±0.306 in the EX527 group;F=37.304,P=0.001),and the degree of myocardial fibrosis(8.515±1.343 in the sham-operation group,23.832±1.095 in the AAC group,13.260±0.

关 键 词：槲皮素 腹主动脉缩窄术 左心室肥厚 

分 类 号：R542.23[医药卫生—心血管疾病]