主 办:北 京 中 医 药 大 学
ISSN 1006-2157 CN 11-3574/R

北京中医药大学学报 ›› 2020, Vol. 43 ›› Issue (8): 668-674.doi: 10.3969/j.issn.1006-2157.2020.08.009

• 中药药理 • 上一篇    下一篇

大黄颗粒对慢性肾脏病大鼠肠道微生态的影响*

罗学文1, 曾玉群2, 王仕琦1, 邹川3, 皮持衡1#   

  1. 1 江西中医药大学附属医院 江西 330006;
    2 浙江省人民医院;
    3 广东省中医院
  • 收稿日期:2020-02-20 出版日期:2020-08-30 发布日期:2020-08-27
  • 通讯作者: # 皮持衡,男,教授,主任医师,主要研究方向:中医药治疗慢性肾脏病,E-mail:13907086560@163.com
  • 作者简介:罗学文,男,博士,副主任中医师
  • 基金资助:
    * 广西自然科学基金项目(No.2014GXNSFBA118166),江西省卫生计生委中医药科研课题(No.2016A124),国家中医药管理局全国老中医药专家学术经验继承工作项目

Effect of Dahuang (rhubarb) Granule on intestinal microecological changes in rats with chronic renal failure*

Luo Xuewen1, Zeng Yuqun2, Wang Shiqi1, Zou Chuan3, Pi Chiheng1#   

  1. 1 The Affiliated Hospital of Jiangxi University of Traditional Chinese Medicine, Jiangxi 330006, China;
    2 Zhejiang Provincial People’s Hospital, Zhejiang 310014, China;
    3 Guangdong Hospital of Traditional Chinese Medicine, Guangdong 510120, China
  • Received:2020-02-20 Online:2020-08-30 Published:2020-08-27
  • Contact: Prof. Pi Chiheng, Chief Physician. No.445 Eight One Street, Nanchang, Jiangxi 330006. The Affiliated Hospital of Jiangxi University of Traditional Chinese Medicine. E-mail: 13907086560@163.com
  • Supported by:
    Natural Science Foundation of Guangxi Province (No.2014GXNSFBA118166), Chinese Medicine Research Project from Health Commission of Jiangxi Province (No.2016A124), Project for Academic Succession of Experience from National Traditional Chinese Medicine Expert, National Administration of Traditional Chinese Medicine

摘要: 目的 研究大黄颗粒对慢性肾脏病大鼠肠道微生态的影响。方法 通过切除大鼠5/6肾造慢性肾脏病模型。大鼠随机分为5组:假手术组,模型组,大黄颗粒低、中、高剂量组。造模4周后取材,检测各组大鼠体重、血尿素氮(BUN)及血肌酐(Crea)水平,新鲜粪便进行4种关键肠道细菌(肠杆菌、肠球菌、乳杆菌及双歧杆菌)培养以及real-time qPCR法定量细菌数量验证,免疫组化法检测结肠紧密连接蛋白、封闭蛋白的表达,液质联用法检测血清硫酸吲哚酚(IS)、鲎试剂法检测血清脂多糖(LPS)水平。结果 与假手术组相比,模型组大鼠BUN、Crea升高(P<0.05);模型组肠杆菌、肠球菌增加(P<0.05)、双歧杆菌减少(P<0.05),结肠上皮claudin-1和occludin蛋白含量减少,血清IS及LPS水平增高(P>0.05)。与模型组相比,大黄颗粒低、中、高剂量组BUN、Crea水平降低(P<0.05),大黄颗粒高剂量组肠杆菌和肠球菌减少、双歧杆菌增加(P<0.05),大黄颗粒低、中、高剂量组结肠上皮claudin-1和occludin蛋白表达增加(P<0.05),大黄颗粒中、高剂量组IS及LPS水平降低(P<0.05)。结论 大黄延缓慢性肾脏病的作用机制可能与其能调节慢性肾脏病大鼠肠道微生态有关,包括增加益生菌双歧杆菌和减少致病菌肠杆菌及肠球菌,增加肠黏膜紧密蛋白claudin-1、occludin的表达,减少肠源性毒素IS以及内毒素LPS水平。

关键词: 大黄颗粒, 慢性肾脏病, 肠道微生态, 肠道菌群, 大鼠

Abstract: Objective To explore the effect of Dahuang (rhubarb) Granule on intestinal microecological changes in rats with chronic renal failure. Methods The 5/6 nephrectomy model was used as chronic renal failure model, and randomly divided into sham operation group, model group, and low-dose, medium-dose, high-dose Dahuang (rhubarb) Granule groups. After 4 weeks, the body weight, blood urea nitrogen (BUN), and blood creatinine (Crea) levels of each group were measured. Four key intestinal bacteria (including E.coli, Enteroroccus, Lactobacillus and Bifidbacteria) were cultured and quantified with the real-time qPCR method. Expression of colonic proteins claudin-1 and occluding was detected with immunohistochemical method. Indole sulfate (IS) and lipopolysaccharide (LPS) levels were detected with liquid chromatography-mass spectrometry and LPS Reagent method. Results Compared with the sham operation group, in the model group renal function indexes of blood urea nitrogen (BUN) and blood creatinine (Crea) were significantly increased (P>0.05); the pathogenic bacteria E.coli and Enteroroccus were significantly increased in the model group (P>0.05), and the probiotics Bifidbacteria was significantly reduced (P>0.05); the levels of claudin-1 and occludin in the colonic epithelium were significantly reduced; the serum IS and LPS levels were significantly increased (P<0.05). Compared with the model group, in the low-dose, medium-dose and high-dose Dahuang (rhubarb) Granule groups, the levels of BUN and Crea were significantly reduced (P>0.05); in the high-dose group, the number of E.coli and Enteroroccus was reduced (P<0.05), while the amount of Bifidbacteria was significantly increased (P<0.05); the expression of claudin-1 and occludin in colonic epithelium was significantly increased in all Dahuang (rhubarb) Granule groups (P<0.05); IS and LPS levels were significantly decreased in the medium-dose and high-dose Dahuang (rhubarb) Granule groups (P<0.05). Conclusion Dahuang (rhubarb) Granule seems to regulate the intestinal microecology in rats with chronic renal failure through regulating the intestinal flora, including increasing the probiotic Bifidbacteria and reducing the pathogenic bacteria E.coli and Enteroroccus, increasing the expression of intestinal mucosal compact proteins claudin-1, occludin, and reducing intestinal toxin IS and endotoxin LPS levels, which potentially improves renal function in rats with chronic renal failure.

Key words: Dahuang (rhubarb) Granule, chronic renal failure, intestinal microecology, intestinal flora, mechanisms, rats

中图分类号: 

  • R285.5