药学学报, 2021, 56(4): 1035-1048
引用本文:
徐卓, 项想, 尚尔鑫, 宿树兰, 郭建明, 钱大玮, 段金廒. 丹参茎叶总酚酸对2型糖尿病肾病小鼠肠道菌群和短链脂肪酸的调节作用[J]. 药学学报, 2021, 56(4): 1035-1048.
XU Zhuo, XIANG Xiang, SHANG Er-xin, SU Shu-lan, GUO Jian-ming, QIAN Da-wei, DUAN Jin-ao. Regulatory effect of total phenolic acid from the stems and leaves of Salvia miltiorrhiza Bge. on intestinal microflora and short-chain fatty acids in type 2 diabetic nephropathy mice[J]. Acta Pharmaceutica Sinica, 2021, 56(4): 1035-1048.

丹参茎叶总酚酸对2型糖尿病肾病小鼠肠道菌群和短链脂肪酸的调节作用
徐卓1, 项想1,2, 尚尔鑫1, 宿树兰1*, 郭建明1, 钱大玮1, 段金廒1*
1. 南京中医药大学, 江苏省中药资源产业化过程协同创新中心, 中药资源产业化与方剂创新药物国家地方联合工程中心, 国家中医药管理局中药资源循环利用重点研究室, 江苏 南京 210023;
2. 中国科学院上海药物研究所, 上海 201203
摘要:
为研究丹参茎叶总酚酸对自发性2型糖尿病肾病小鼠的肠道菌群和短链脂肪酸的调节作用,以db/db小鼠为研究对象,进行丹参总酚酸干预。动物福利和实验过程均遵循南京中医药大学药物安全性评价研究中心动物伦理委员会的规定。采集小鼠新鲜粪便及盲肠内容物进行肠道菌群组成和差异菌群等分析;采用气相色谱法检测短链脂肪酸含量,并与肠道菌群进行相关性分析。结果表明,与空白组相比,模型组小鼠两类样本中下降最显著的差异菌群分别是g_Rikenellaceae_RC9_gut_groupg_Bacteroidales_S24-7_group;上升最显著的分别是g_unclassified_f__Coriobacteriaceaeg_unclassified_p__Firmicutes。模型组小鼠新鲜粪便中的异戊酸和戊酸以及盲肠内容物中6种短链脂肪酸含量显著减少(P<0.01)。药物干预后,肠道菌群紊乱和短链脂肪酸减少情况均有不同程度改善,且丹参茎叶总酚酸组对部分菌群和短链脂肪酸的调节作用略优于丹参根总酚酸组。相关性分析结果显示,g_Rikenellaceae_RC9_gut_group与盲肠内容物中的乙酸和异丁酸均呈中度正相关(r>0.4),提示丹参茎叶总酚酸可改善2型糖尿病肾病小鼠肠道菌群紊乱,并可通过调节部分产短链脂肪酸菌含量回调肠道内短链脂肪酸的含量,从而有助于恢复正常。
关键词:    丹参茎叶      酚酸类成分      2型糖尿病      短链脂肪酸      糖尿病肾病      肠道菌群     
Regulatory effect of total phenolic acid from the stems and leaves of Salvia miltiorrhiza Bge. on intestinal microflora and short-chain fatty acids in type 2 diabetic nephropathy mice
XU Zhuo1, XIANG Xiang1,2, SHANG Er-xin1, SU Shu-lan1*, GUO Jian-ming1, QIAN Da-wei1, DUAN Jin-ao1*
1. Jiangsu Collaborative Innovation Center of Chinese Medicinal Resources Industrialization, National and Local Collaborative Engineering Center of Chinese Medicinal Resources Industrialization and Formulae Innovative Medicine, State Administration of Traditional Chinese Medicine Key Laboratory of Chinese Medicinal Resources Recycling Utilization, Nanjing University of Chinese Medicine, Nanjing 210023, China;
2. Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China
Abstract:
To study the regulating effect of total phenolic acids from the stems and leaves of Salvia miltiorrhiza Bge. on the intestinal flora and short-chain fatty acids in spontaneous type 2 diabetic nephropathy mice, db/db mice were taken as the research object, and were treated with the total phenolic acid of Salvia miltiorrhiza Bge. Animal welfare and experimental procedures followed the regulations of the Animal Ethics Committee of Nanjing University of Chinese Medicine Drug Safety Evaluation Research Center. Fresh feces and cecal contents of mice were collected for analysis of intestinal flora composition and differential flora. Gas chromatography was used to detect short-chain fatty acids in fresh feces and cecal content. Then the correlation analysis of the two results was made. Compared with the normal group, the most significant decreased differential flora in the model group were g_Rikenellaceae_RC9_gut_group and g_Bacteroidales_S24-7_group, while the most significant increased were g_unclassified_f__Coriobacteriaceae and g_unclassified_p__Firmicutes. Compared with the blank group, the contents of isovaleric acid and valeric acid in fresh feces and the contents of 6 short-chain fatty acids in the cecal contents of the model group were significantly reduced (P<0.01). After drug intervention, the intestinal flora disorder and the reduction of short-chain fatty acids were improved to varying degrees, and the effect of the total phenolic acids from the stems and leaves of Salvia miltiorrhiza Bge. was slightly better than that from the roots in regulating some flora and short-chain fatty acids. The results of correlation analysis showed that g_Rikenellaceae_RC9_gut_group was moderately positively correlated with acetic acid and isobutyric acid in the cecal contents (r>0.4). It is suggested that the total phenolic acid from the stems and leaves of Salvia miltiorrhiza Bge. can improve the intestinal flora disorder of mice with type 2 diabetic nephropathy, and can regulate the content of short-chain fatty acids in the intestine via adjusting the content of some short-chain fatty acid-producing bacteria, thereby helping to restore normal.
Key words:    stem and leave of Salvia miltiorrhiza Bge.    phenolic acid    type 2 diabetes mellitus    short-chain fatty acid    diabetic nephropathy    intestinal microflora   
收稿日期: 2020-07-29
DOI: 10.16438/j.0513-4870.2020-1259
基金项目: 国家自然科学基金资助项目(81673533,81973708).
通讯作者: 宿树兰,Tel:13809043258,E-mail:sushulan@njucm.edu.cn;段金廒,Tel:86-25-85811291,E-mail:dja@njucm.edu.cn
Email: sushulan@njucm.edu.cn;dja@njucm.edu.cn
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