白藜芦醇通过改变肠道菌群谱改善压力超负荷大鼠心室功能  

Mechanism of resveratrol inhibiting cardiac remodeling by regulating gut microbiota in pressure overload rats

作　　者：李泽聪 马中富[1] LI Ze-cong;MA Zhong-fu(Department of General Medicine,the First Affiliated Hospital of Sun Yat-sen University,Guangzhou,Guangdong 510080;Department of General Medicine,Caihong Community Health Service Center,Liwan District,Guangzhou,Guangzhou,Guangdong 510000)

机构地区：[1]中山大学附属第一医院全科医学科,广东广州510080 [2]广州市荔湾区彩虹街社区卫生服务中心全科医学部,广东广州510000

出　　处：《热带医学杂志》2021年第10期1242-1247,F0003,共7页Journal of Tropical Medicine

基　　金：广州市科技计划项目(201300000160);第三军医大学2020年度“创伤、烧伤与复合伤国家重点实验室开放基金”(SKLKF202021)。

摘　　要：目的研究白藜芦醇(RSV)通过重构肠道菌群对心力衰竭(HF)大鼠心脏重构的影响。方法将18只SD大鼠随机分为对照组、HF组和RSV组,每组6只。采用腹主动脉缩窄术(TAC)构建HF大鼠模型,RSV组给予RSV(4mg/kg)连续灌胃12周,利用超声心动图评价心脏结构和心功能;苏木精-伊红染色法(HE)、Masson染色和天狼猩红染色观察心肌组织病理学变化,计算心肌胶原容积分数(CVF)和血管周围胶原面积(PVCA)来评价心肌纤维化程度;酶联免疫吸附法(ELISA)检测血清氨基末端脑钠肽前体(NT-proBNP)水平;运用16S rRNA测序观察肠道菌群的变化;用稳定同位素稀释液相色谱质联用(LC-MS)评价血浆氧化三甲胺(TMAO)水平。结果与HF组比较,RSV组大鼠的皮毛、呼吸、活动度等一般情况得到改善,心脏的左心室舒张未期内径和左心室收缩未期内径明显减少,左心室射血分数和左心室短轴缩短率明显增加,血清NT-proBNP含量降低,血浆TMAO含量明显降低(P<0.05)。与HF组比较,RSV组大鼠的心肌细胞排列及形态稍完整,心肌细胞肿胀和细胞核溶解均明显改善,且心肌纤维化程度也得到改善。在肠道菌群方面,与HF组比较,RSV组大鼠的梭菌目、乳杆菌属、劳特氏菌更丰富。结论 RSV可改善TAC诱导的HF大鼠心室功能,其作用机制可能部分归因于肠道微生物群的组成和功能的变化可能与重构肠道菌群有关。Objective To study the effect of resveratrol(RSV)on cardiac remodeling in rats with heart failure(HF)via remodeling of the gut microbiota. Methods 18 male 6-week-old SD rats were randomly divided into Sham group,HF group and RSV group. Transverse aortic constriction(TAC)surgery was performed to induce pressure overload rat model. RSV(4 mg/kg)was administrated to HF rats for 12 weeks. Cardiac structure and heart function were observed by echocardiography.Pathological changes of myocardium were observed by HE staining,MASSON staining and Sirus red staining. Myocardial collagen volume fraction(CVF)and perivascular collagen area(PVCA)of myocardial tissues were calculated to evaluate myocardial fibrosis. The N-terminal pro-brain natriuretic peptide(NT-proBNP)and trimethylamine oxide(TMAO)were measured by enzyme-linked immuno sorbent assay(ELISA) and liquid chromatography mass spectrometry(LC-MS)respectively. Finally,the rat feces in the cecum were acquired for the detection of intestinal flora by 16 Sr RNA sequencing.Results Compared with HF group,the general conditions of fur,respiration and activity of RSV intervention group were improved;left ventricular internal dimensions at diastole(LVIDd) and left ventricular internal dimensions at systole(LVIDs)of heart were significantly reduced;left ventricular ejection fraction(LVEF)and left ventricular fraction shortening(LVFS)were significantly increased;the content of serum NT-proBNP and plasma TMAO were significantly decreased(P<0.05). In addition,compared with HF rats,the arrangement and morphology of cardiomyocytes in RSV intervention group were slightly complete;the swelling and nucleolysis of cardiomyocytes were significantly improved,and the degree of myocardial fibrosis was also improved. In terms of intestinal flora,compared with HF rats,rats in RSV intervention group were more abundant in clostridiales,Lactobacillus and Blautia. Conclusion RSV improved cardiac remodeling in HF rats induced by TAC,and its mechanism might be related to the remodeling of gut microb

关 键 词：白藜芦醇 心室重构 肠道菌群 TMAO 益生元 

分 类 号：R541.61[医药卫生—心血管疾病] K285[医药卫生—内科学]