海昆肾喜胶囊调控肠道菌群改善慢性肾衰竭大鼠肾功能及肾脏损伤OA

Objective:To investigate the improvement of renal function and renal injury in rats with chronic renal failure by regulating the intestinal flora via Haikun Shenxi Capsules(海昆肾喜胶囊)using metagenomics technology.Methods:Forty male Sprague Dawley(SD)rats were randomly divided into a normal control group,a model group,a NiaoDuQing(尿毒清)group of 2.5 g/kg,and Haikun Shenxi Capsules groups of 100 mg/kg and 200 mg/kg.Except for the normal control group,the rat models of chronic renal failure were established by intragastric administration of ade-nine suspension at a dose of 200 mg/kg for four weeks.After successful modeling,rats were administered for four weeks,and the blood,urine,kidney,and feces samples were collected.The renal function indices,including blood urea nitrogen(BUN),serum creatinine(SCr),24 h urinary protein volume(24 h UTP),uric acid(UA),and urinary creatinine(UCR),as well as the renal anemia indices,including red blood cell count(RBC),hemoglobin(HGB),and hematocrit(HCT)were detected.Hematoxylin-eosin(HE)staining was performed on the kidney to observe the pathological state of the rat kidneys in each group,while feces were sequenced and analyzed for intestinal flora by metagenomic technology.Results:Compared with those in the normal control group,the BUN and SCr levels in the model group were significantly increased(P＜0.01),indicating that the model construction was successful.After drug administration,compared with the normal control group,the model group showed a reduced number of glomeruli and severe tubular damage.The level of BUN,SCr,24 h UTP,and UA was significantly increased(P＜0.01),while the level of UCR,RBC,HGB,and HCT was significantly decreased(P＜0.01).Compared with the model group,the Haikun Shenxi Capsules group of 200 mg/kg was able to improve the renal pathological changes and restore the tubular morphology.The level of BUN,SCr,24 h UTP,and UA was significantly reduced(P＜0.01),and the level of UCR,RBC,HGB,and HCT was significantly in-creased(P＜0.01).The intestinal flora sequencing diversity analysis by metagenomics showed,at the species level,the relative abundance of Ligilactobacillus murinus,Bacteroides acidifaciens,and Bacteroides_sp.was decreased in the model group,while the relative abundance of Prevotella_sp.and Oscillospiraceae_bacterium was increased(P＜0.05).Haikun Shenxi Capsules could increase the relative abundance of Ligilactobacillus murinus and Bacteroides_sp,and the relative a-bundance of Bacteroides acidifaciens was significantly higher than that of the model group(P＜0.05).Kyoto Encyclope-dia of Genes and Genomes(KEGG)enrichment analysis showed that the functional pathways of sugar biosynthesis and metabolism,carbohydrate digestion and absorption,and pyruvate metabolism were upregulated after treatment with Haikun Shenxi Capsules.Conclusion:Haikun Shenxi Capsules can improve renal function and histopathological abnormalities in rats with chronic renal failure,which may be related to modulating the ratio of intestinal beneficial bacteria to pathogenic bacteria and enhancing functional pathways of sugar biosynthesis and metabolism,carbohydrate digestion and absorption,as well as pyruvate metabolism.