Exploring the Mechanism of Action of Xinmailong Injection on Rats with Chronic Heart Failure Based on Intestinal Flora
OBJECTIVE To study the effects and mechanisms of Xinmailong injection on doxorubicin induced chronic heart failure in rats based on intestinal flora.METHODS Forty-eight SD rats were randomly divided into normal group,model group,digoxin group(0.025 mg·kg-1),and the low,medium,and high dose groups of Xinmailong injection(60,120,and 240 mg·kg-1),8 rats in each group.The rats in all groups except the normal group were modeled by intraperitoneal injection of 2 mg·kg-1 doxorubicin twice a week for 6 weeks,followed by pharmacological intervention for 14 d.Ultrasonic cardiogram was performed on each group of rats to determine the left ventricular ejection fraction(LVEF)and shortening fraction(FS),which were indicators of cardiac function;blood was taken from the abdominal aorta and serum was collected from the rats to determine the levels of serum biochemical indicators of diamine oxidase(DAO)and D-lactic acid(D-LA);heart samples were collected and stained with HE to observe the myocardial histopathological changes in the rats in each group;and feces were collected from the rats and analyzed for the species variability of the rat flora by 16S rDNA sequencing technology.RESULTS Compared with the normal group,LVEF and FS were significantly decreased in the model group(P＜0.01);compared with the model group,they were significantly elevated in the low,medium,and high dose groups of Xinmailong injection and digoxin group(P＜0.01).Compared with the normal group,DAO and D-LA levels were significantly increased in the model group(P＜0.01);compared with the model group,they were significantly decreased in the low,medium,and high dose groups of Xinmailong injection and digoxin group(P＜0.01).Compared with the normal group,cardiomyocytes in the model group showed edema,degeneration,necrosis,and disordered arrangement,etc.Compared with the model group,the morphology of cardiomyocytes in the high dose group of Xinmailong injection and digoxin group was basically normal,and no obvious pathological damage changes were seen,while morphological changes of cardiomyocytes could be seen in the medium and low-dose groups of Xinmailong injection and were more obvious in the low-dose group.The results of the intestinal flora showed that the Alpha diversity of the intestinal flora in the model group decreased compared with the normal group,and the structure of the intestinal flora,the dominant bacteria,and the abundance of each bacterial group produced changes,and at the level of phylum,the abundance of the Spirochaetes increased significantly,and the abundance of the Bacteroidota decreased.At the genus level,the model group showed an increase in the abundance of Allobaculum and Treponema,and the abundance of Bifidobacterium,Prevotellaceae_Prevotella and Ruminococcaceae_Ruminococcus and other flora abundance decreased significantly.Compared with the model group,the Xinmailong injection group was able to reduce potential pathogenic bacteria and increase the percentage of beneficial bacteria,regulating the intestinal flora.CONCLUSION Xinmailong injection can improve adriamycin induced chronic heart failure,and its mechanism of action may be related to the regulation of intestinal barrier function and improvement of intestinal flora disorders.
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