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目的:采用宏基因组学技术探究海昆肾喜胶囊通过调节肠道菌群改善慢性肾衰竭大鼠肾功能及肾脏损伤。方法:40只雄性SD大鼠，随机分为正常对照组、模型对照组、尿毒清2.5 g/kg组和海昆肾喜胶囊0.1、0.2 g/kg组，除正常对照组外均采用腺嘌呤混悬液0.2 g/kg灌胃4周的方法制备慢性肾衰竭大鼠模型。模型构建成功后，给药干预4周，收集大鼠血液、尿液、肾脏及粪便样本，检测肾功能指标血清尿素氮(BUN)、血清肌酐(SCr)、血清尿酸(UA)、24 h尿蛋白量(24 h UTP)、尿肌酐(UCr)含量，肾性贫血指标红细胞数目(RBC)、血红蛋白(HGB)、红细胞压积(HCT);HE染色观察大鼠肾脏病理状态；粪便采用宏基因组技术对肠道菌群进行测序分析。结果:与正常对照组相比，模型对照组肾小球数量减少，肾小管损伤严重，血清BUN、SCr、UA、尿液24 h UTP含量显著升高(P<0.01),尿液UCr含量降低，全血中RBC数量、HGB含量、HCT百分率显著降低(P<0.01);与模型对照组相比，海昆肾喜胶囊0.2 g/kg组肾脏病理情况改善、肾小管形态恢复，血清BUN、SCr、UA、尿液24 h UTP含量显著降低(P<0.01),尿液UCr含量升高，全血中RBC数量、HGB含量、HCT百分率升高(P<0.01)。宏基因组肠道菌群测序多样性分析显示，种水平上，模型对照组大鼠宿主关联乳杆菌、产酸拟杆菌、拟杆菌的相对丰度降低，普雷沃氏菌、颤螺菌的相对丰度升高(P<0.05);海昆肾喜胶囊大鼠宿主关联乳杆菌、拟杆菌的相对丰度有升高趋势，产酸拟杆菌相对丰度明显高于模型对照组(P<0.05)。KEGG功能富集分析显示，经海昆肾喜胶囊治疗后，大鼠肠道糖的生物合成和代谢、碳水化合物消化吸收、丙酮酸代谢等功能上调。结论:海昆肾喜胶囊能够改善慢性肾衰竭大鼠的肾脏功能以及病理状况，可能与调节肠道有益菌与致病菌比例、调节糖的生物合成和代谢、碳水化合物消化吸收、丙酮酸代谢等功能途径有关。
Abstract：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 adenine 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 increased(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 abundance of Bacteroides acidifaciens was significantly higher than that of the model group(P<0.05). Kyoto Encyclopedia 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.
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基本信息:
DOI：10.13412/j.cnki.zyyl.20251011.002
中图分类号:R285.5
引用信息:
[1]李之煊,张洪雄,孙艳,等.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[J].中药药理与临床,2026,42(08):12-21.DOI:10.13412/j.cnki.zyyl.20251011.002.
基金信息:
山西省科技厅基础研究项目(编号：202303021221163); 中华中医药学会联合攻关项目(编号：2023DYPLHGG-13); 山西省地产中药品质评价技术创新中心(晋科函[2022]168号); 山西中医药大学中药分析学二级学科建设项目
2025-10-13
2025-10-13
2025-10-13