基于肠道菌群代谢产物的变化探讨芪苈强心胶囊改善心肌纤维化的机制  

Mechanism of Qili Qiangxin capsule in improving myocardial fibrosis:a study based on changes in gut microbiota metabolites

作　　者：陈云[1] 焦雪妍 兰真真 张宁[2] 张艺凡 刘璐瑶 刘姝彤 刘新灿[1] Chen Yun;Jiao Xueyan;Lan Zhenzhen;Zhang Ning;Zhang Yifan;Liu Luyao;Liu Shutong;Liu Xincan(Heart Center,First Affiliated Hospital of Henan University of Traditional Chinese Medicine,Zhengzhou 450000,Henan Province,China)

机构地区：[1]河南中医药大学第一附属医院心脏中心,郑州450000 [2]河南中医药大学 [3]郑州大学

出　　处：《中华老年心脑血管病杂志》2024年第4期445-449,共5页Chinese Journal of Geriatric Heart,Brain and Vessel Diseases

基　　金：河南省青年人才托举工程(2021HYTP057);河南省中医药科学研究专项(2023ZXZX1156)。

摘　　要：目的从肠道菌群代谢产物氧化三甲胺(TMAO)、脂多糖(LPS)的变化角度探讨芪苈强心胶囊对心肌梗死后大鼠心肌纤维化的影响和作用机制。方法将60只大鼠随机分为假手术组、模型组、芪苈强心高剂量组(1.0 g/kg)、芪苈强心中剂量组(0.5 g/kg)、芪苈强心低剂量组(0.25 g/kg)、培哚普利组(0.84 mg/kg),每组10只。造模时死亡13只,灌胃时死亡5只,最终假手术组8只,模型组8只,芪苈强心高剂量组7只,芪苈强心中剂量组6只,芪苈强心低剂量组7只,培哚普利组6只。超声心动图检测各组大鼠的左心室射血分数(LVEF)、左心室短轴缩短率(LVFS)、左心室舒张末期内径(LVEDD)、左心室收缩末期内径(LVEDS),苏木精-伊红染色检测心肌与回肠组织的病理形态,Masson染色检测心肌纤维化程度,计算心肌胶原容积分数(CVF),液相色谱-质谱法检测血浆TMAO的含量,酶联免疫吸附测定可溶性生长刺激表达基因2蛋白(sST2)和LPS的含量。结果与假手术组比较,模型组大鼠LVFS、LVEF显著降低,LVEDD、LVEDS、sST2、TMAO、LPS显著升高(P<0.05,P<0.01);与模型组比较,芪苈强心高、中、低剂量组及培哚普利组大鼠LVFS、LVEF显著升高,芪苈强心高剂量组大鼠血浆sST2浓度[(2025.45±413.13)pg/ml vs(2800.86±208.64)pg/ml]、血浆TMAO含量[(351.68±129.01)ng/ml vs(641.41±188.44)ng/ml]、血浆LPS浓度[(420.22±62.32)EU/L vs(594.62±83.40)EU/L]显著降低(P<0.05,P<0.01)。结论芪苈强心胶囊可能通过抑制肠道菌群代谢产物TMAO、LPS改善心肌纤维化,具体机制还需进一步探究。Objective To investigate the effects of Qili Qiangxin capsule on myocardial fibrosis in rats after myocardial infarction(MI)from the perspective of the changes in gut microbiota metabolites trimethylamine N-oxide(TMAO)and lipopolysaccharide(LPS).Methods Sixty rats were randomly divided into sham operation group,model group,high-,medium-and low-dose Qili Qiangxin groups(1.0,0.5 and 0.25 g/kg),and perindopril group(0.84 mg/kg),with 10 rats in each group.Because 13 rats died during modeling,and 5 rats died during gavage,and finally,there were 8 rats in sham operation group,8 rats in model group,7,6 and 6 rats respectively in the high-,medium-and low-dose Qili Qiangxin groups,and 6 rats in perindopril group.Echocardiography was used to detect the left ventricular ejection fraction(LVEF),left ventricular short axis shortening rate(FS),left ventricular end diastolic diameter(LVEDD)and left ventricular end systolic diameter(LVEDS).HE staining was used to observe the pathological morphology of myocardial and ileal tissues,and Masson staining was employed to detect myocardial fibrosis to calculate myocardial collagen volume fraction(CVF).The plasma content of TMAO was detected by liquid chromatography-mass spectrometry,and the contents of soluble growth stimulation expression gene 2 protein(sST2)and LPS was determined by ELISA.Results Compared with the sham operation group,the model group had significantly decreased LVEF and FS,and increased LVEDD,LVEDS,sST2,TMAO,and LPS(P<0.01).Compared with the model group,FS and LVEF in the high and medium-dose Qili Qiangxin groups and perindopril group were significantly increased(P<0.01);the plasma sST2 content of the high-dose Qili Qiangxin group was significantly decreased(2025.45±413.13 pg/ml vs 2800.86±208.64 pg/ml,P<0.01),the plasma TMAO content was significantly decreased(351.68±129.01 ng/ml vs 641.41±188.44 ng/ml,P<0.01),and the plasma LPS content was significantly decreased(420.22±62.32 EU/L vs 594.62±83.4 EU/L,P<0.05).Conclusion Qili Qiangxin capsule may improve myocar

关 键 词：心肌梗死 芪苈强心胶囊 心内膜心肌纤维化症 胃肠道微生物组 脂多糖类 氧化三甲胺 

分 类 号：R285.5[医药卫生—中药学]