【摘要】 目的 研究Klotho(KL)蛋白对急性心肌梗死(以下简称心梗)小鼠肠道菌群及心功能的影响。方法 将24只6周龄雄性C57BL/6小鼠按照随机数字表法分为3组，即心梗组、KL组和对照组。心梗组和KL组小鼠接受急性心肌梗死手术，对照组小鼠接受假手术，术后每组均存活7只小鼠。术后第2天起对KL组小鼠腹腔注射KL(20ng/kg),每两天注射1次，心梗组和对照组小鼠腹腔注射0.9%氯化钠溶液(15ml/kg),30天后对小鼠进行超声心动图检查；取小鼠肠道内粪便进行16S rDNA基因测序，分析菌群的α多样性、β多样性和菌群结构；采集小鼠心肌组织，采用实时荧光定量聚合酶链反应(real-time quantitative polymerase chain reaction, RT-qPCR)技术检测小鼠心肌B型脑钠肽(B-type natriuretic peptide, BNP)、肿瘤坏死因子-α(tumor necrosis factor-α, TNF-α)和转化生长因子-β1(trarisforming growth factor-β1, TGF-β1)的mRNA的表达水平。结果 主成分分析(principal component analysis, PCA)表明，KL组与心梗组小鼠肠道菌群构成上存在明显差异。门水平上，心梗组较对照组小鼠拟杆菌门相对丰度增高，厚壁菌门相对丰度降低；属水平上，心梗组小鼠Muri菌增加，毛螺菌科NK4A136组菌群减少。经过KL治疗后，上述菌群相对丰度均得到一定的改善。KL组较其他两组Epsilonbacteraeota菌门、杜氏杆菌和幽门螺杆菌相对丰度均明显升高。在BNP、TNF-α和TGF-β1mRNA的表达上，KL组较心梗组有明显下降。超声心动图结果显示，KL组左心室射血分数和缩短分数均较心梗组明显改善。结论 KL具有改善急性心肌梗死小鼠肠道菌群紊乱和心功能的作用，为KL的实际应用提供了新的思路和依据。更多还原

【Abstract】 Objective To evaluate the effects of Klotho(KL) protein on intestinal flora and cardiac function in mice with acute myocardial infarction(AMI). Methods Twenty-four 6-week male C57BL/6mice were randomly divided into three groups: MI group, KL group and control group. Mice in MI group and KL group received AMI operation, while control group received sham operation. Seven mice survived in each group after operation. KL(20ng/kg) was injected intraperitoneally in KL group from the second day after operation, once every two days, and 0.9% sodium chloride solution(15ml/kg) was injected intraperitoneally in the other two groups. After 30days, the mice were examined by echocardiography and the feces of mice were taken for 16S rDNA gene sequencing, analyzed the α diversity, β diversity and structural features of gut microbiota. The myocardial tissue of mice was collected and the mRNA expression of B-type natriuretic peptide(BNP), tumor necrosis factor-α(TNF-α) and trarisforming growth factor-β1(TGF-β1) in mice myocardium was detected by real-time quantitative polymerase chain reaction(RT-qPCR) technique. Results Principal component analysis(PCA) showed that there were significant differences in the composition of intestinal flora between KL group and MI group. At the phylum level, the relative abundance of bacteroidetes in MI group was higher than that in control group, and the relative abundance of firmicutes was lower. At the genus level, mice in MI group had more muribaculaceae and less lachnospiraceae＿NK4A136. After KL treatment, the relative abundance of the above flora was improved to some extent. At the same time, we found that the relative abundance of epsilonbacteraeota, dubosiella and helicobacter in KL group was significantly higher than that in the other two groups. The mRNA expression of BNP, TNF-α and TGF-β1 in KL group was significantly lower than that in MI group. The results of echocardiography showed that the left ventricular ejection fraction and fractional shortening in KL group were significantly improved compared with those in MI group. Conclusion KL can improve the disturbance of intestinal flora and cardiac function in mice with AMI, which provides a new idea and basis for the practical application of KL.更多还原