苓桂术甘汤对压力负荷致心衰小鼠心功能、肠道屏障和菌群的影响  

Effect of Linggui Zhugan Decoction on Intestinal Barrier and Intestinal Flora in Mice with Pressure Overload-Induced Heart Failure

作　　者：张红霞[1] 陈瑶 赵鑫[2] 邱先哲 李玉红[2] ZHANG Hongxia;CHEN Yao;ZHAO Xin;QIU Xianzhe;LI Yuhong(The Second Affiliated Hospital of Tianjin University of Traditional Chinese Medicine,Tianjin 300250,China;Tianjin University of Traditional Chinese Medicine,Tianjin 301617,China)

机构地区：[1]天津中医药大学第二附属医院,天津300250 [2]天津中医药大学,天津301617

出　　处：《中医药信息》2023年第2期23-30,共8页Information on Traditional Chinese Medicine

基　　金：全国中医药创新骨干人才培训项目([2019]128);第五批全国中医优秀人才研修项目([2022]1);天津市卫生健康委员会中医药重点领域科研项目(2020010)。

摘　　要：目的:探讨苓桂术甘汤对心力衰竭小鼠心功能、肠道屏障和菌群的影响。方法:采用主动脉弓缩窄术(transverse aortic constriction,TAC)复制心衰小鼠模型,术后1周,将小鼠随机分为假手术组(Sham,n=7)、TAC模型组(TAC,n=7)、苓桂术甘汤低剂量组(LD-L,n=6,4.29 g/kg)和苓桂术甘汤高剂量组(LD-H,n=7,8.58 g/kg),每日灌胃给药共8周。采用小动物超声、Western blot和16S rRNA高通量测序分别检测小鼠心功能、结肠组织中ZO-1及Occludin蛋白表达、粪便菌群。结果:与Sham组比较,TAC小鼠左室舒张末期内径(LVEDD)、左室收缩末期内径(LVESD)显著升高;射血分数(EF)、短轴缩短率(FS)和ZO-1、Occludin蛋白表达显著降低。与TAC组比较,苓桂术甘汤治疗组能显著降低LVEDD、LVESD,升高EF、FS,上调ZO-1、Occludin蛋白表达。16S rRNA测序结果显示,与Sham组比较,TAC组小鼠肠道细菌丰度和多样性降低,苓桂术甘汤治疗组可以增加心衰小鼠肠道细菌丰度和多样性,调节肠道细菌结构紊乱,增加与短链脂肪酸产生密切相关的菌属如norank_f_Muribaculaceae、Prevotellaceae_NK3B31_group的丰度。结论:苓桂术甘汤可以显著改善心衰小鼠的心功能,修复肠黏膜屏障,调节肠道细菌结构紊乱,促进短链脂肪酸产生相关菌的生长。Objective:To investigate the effect of Linggui Zhugan Decoction on heart function,intestinal barrier and intestinal flora in mice with transverse aortic constriction(TAC)-induced heart failure(HF).Methods:TAC surgery was utilized to establish the mice model of HF.One week after TAC,the mice were randomly divided into the sham group(n=7),the model group(n=7),the Linggui Zhugan Decoction group of low-dose(n=6,4.29 g/kg),and the Linggui Zhugan Decoction group of high-dose(n=7,8.58 g/kg).After 8 weeks of administration,echocardiography,Western blot and high-throughput 16S rRNA sequencing analysis were used to evaluate cardiac function of mice,the protein expressions of ZO-1 and Occludin in colonic tissues,and intestinal flora in feces,respectively.Results:Compared with those in the sham group,the values of LVEDD,LVESD,EF and FS,as well as the protein expressions of ZO-1 and Occludin were significantly decreased in the model group.Compared with those in the model group,the values of LVEDD and LVESD were significantly decreased,the values of EF and FS were significantly increased,and the protein expressions of ZO-1 and Occludin were significantly up-regulated in the Linggui Zhugan Decoction groups.16S rRNA sequencing results showed that the intestinal flora abundance and diversity were markedly decreased in the model group compared with those in the sham group,which significantly increased after the intervention of Linggui Zhugan Decoction.Linggui Zhugan Decoction could also regulate the disorder of intestinal bacterial structure in HF mice,and increase the abundance of bacteria which are closely related to the production of short chain fatty acids,including norank_f_Muribaculaceae and Prevotellaceae_NK3B31_group.Conclusion:Linggui Zhugan Decoction significantly improves the cardiac function of HF mice,repairs the function of intestinal mucosal barrier,regulates the structural disorder of intestinal flora and promotes the growth of bacteria related to the production of short chain fatty acids.

关 键 词：苓桂术甘汤 心力衰竭 主动脉弓缩窄术 肠道菌群 肠道屏障 

分 类 号：R285.5[医药卫生—中药学]