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杨诗尧, 李鸿, 黎柳, 谭丹妮, 刘秀, 向琴, 黄秋晴, 邹俊驹, 喻嵘.当归芍药散对糖尿病肾病db/db小鼠肠道菌群的作用[J].湖南中医药大学学报,2024,44(12):2172-2182[点击复制] |
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当归芍药散对糖尿病肾病db/db小鼠肠道菌群的作用 |
杨诗尧,李鸿,黎柳,谭丹妮,刘秀,向琴,黄秋晴,邹俊驹,喻嵘 |
(湖南中医药大学中医学院, 湖南 长沙 410208;湖南中医药大学中医方证研究转化医学湖南省重点实验室, 湖南 长沙 410208;湖南中医药大学科技处, 湖南 长沙 410208) |
摘要: |
目的 研究当归芍药散(Danggui Shaoyao San,DSS)对糖尿病肾病小鼠肠道菌群的作用。方法 选取30只8周龄雄性db/db小鼠,6只8周龄雄性db/m小鼠。检测空腹血糖以及尿白蛋白/肌酐比值(urinary albumin to creatinine ratio,UACR),将符合要求的db/db小鼠随机分成5组:模型(MOD)组(0.1 mL/10 g蒸馏水)、达格列净(DAPA)组(1.3 mg/kg达格列净片)及DSS低剂量(DSS-L)组(8.39 g/kg)、中剂量(DSS-M)组(16.77 g/kg)、高剂量(DSS-H)组(33.54 g/kg),每组6只;6只db/m小鼠为空白对照(CON)组(0.1 mL/10 g蒸馏水)。测定小鼠空腹血糖、胰岛素耐量;ELISA法测定血尿素氮和血肌酐;全自动生化分析仪检测UACR;对小鼠的肾脏组织和小肠组织进行HE染色;取小鼠结肠粪便进行16S rRNA测序。结果 与CON组比较,MOD组糖耐量下降,空腹血糖、血尿素氮、血肌酐、UACR升高(P<0.01);与MOD组比较,DSS组的糖耐量升高(P<0.01),空腹血糖、血尿素氮、血肌酐、UACR降低(P<0.01),肾脏和小肠的病理损伤程度降低。肠道菌群多样性研究结果显示:相比CON组,MOD组肠道菌群多样性降低;相比MOD组,DSS-M组与CON组的菌群差异性较小。在菌群的物种组成方面,DSS-M组小鼠嗜黏蛋白阿克曼氏菌(Akkermansia muciniphila)的相对丰度明显增加(P<0.01)。结论 DSS能显著增加糖尿病肾病db/db小鼠肠道中的嗜黏蛋白阿克曼氏菌的丰度,可能是其改善糖尿病肾病的机制之一。 |
关键词: 糖尿病肾病 当归芍药散 肠道菌群 活血利水法 糖尿病 16S rRNA 中医药 |
DOI:10.3969/j.issn.1674-070X.2024.12.005 |
投稿时间:2024-09-13 |
基金项目:国家自然科学基金项目(U21A20411,82074400);湖南省自然科学基金创新研究群体项目(2024JJ1007);湖南中医药大学学科建设“揭榜挂帅”项目(22JBZ002);湖南省研究生科研创新项目(CX20220778)。 |
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Effects of Danggui Shaoyao San on the intestinal flora of db/db mice with diabetic nephropathy |
YANG Shiyao, LI Hong, LI Liu, TAN Danni, LIU Xiu, XIANG Qin, HUANG Qiuqing, ZOU Junju, YU Rong |
(School of Traditional Chinese Medicine, Hunan University of Chinese Medicine, Changsha, Hunan 410208, China;Hunan Key Laboratory of Traditional Chinese Medicine Prescription and Syndromes Translational Medicine, Hunan University of Chinese Medicine, Changsha, Hunan 410208, China;Office of Science & Technology, Hunan University of Chinese Medicine, Changsha, Hunan 410208, China) |
Abstract: |
Objective To study the effects of Danggui Shaoyao San (DSS) on the intestinal flora of mice with diabetic nephropathy (DN). Methods Thirty 8-week-old male db/db mice and six 8-week-old male db/m mice were selected. Fasting blood glucose (FBG) and urinary albumin to creatinine ratio (UACR) were measured, and the qualified db/db mice were randomized into five groups: model (MOD) group (distilled water 0.1 mL/10 g), dapagliflozin (DAPA) group (dapagliflozin tablets 1.3 mg/kg), low-dose DSS (DSS-L) group (8.39 g/kg), medium-dose DSS (DSS-M) group (16.77 g/kg), and high-dose DSS (DSS-H) group (33.54 g/kg), with six mice in each group. The six db/m mice served as the blank control (CON) group (distilled water 0.1 mL/10 g). Then FBG and insulin tolerance in mice were measured. Blood urea nitrogen (BUN) and serum creatinine (Scr) were measured by ELISA, and UACR was detected by fully automatic biochemical analyzer. Samples of the mouse renal and small intestinal tissues were taken for HE staining, and feces in the mouse colon was selected for 16S rRNA sequencing. Results Compared with the CON group, the MOD group had lower glucose tolerance and higher levels of FBG, BUN, Scr, and UACR (P<0.01). Compared with the MOD group, the DSS group exhibited increased glucose tolerance (P<0.01), decreased levels of FBG, BUN, Scr, and UACR (P<0.01), and reduced pathological damage to the kidney and small intestine. The study on the intestinal flora diversity show that compared with the CON group, the MOD group had a lower diversity of intestinal flora. Compared with the MOD group, the flora differences between the DSS-M group and the CON group were smaller. In terms of the species composition of the flora, the relative abundance of Akkermansia muciniphila in the DSS-M group of mice was significantly higher (P<0.01). Conclusions DSS can significantly increase the abundance of Akkermansia muciniphila in the intestines of db/db mice with DN, which may be one of the mechanisms by which it improves DN. |
Key words: diabetic nephropathy Danggui Shaoyao San intestinal flora circulating blood and draining water retention diabetes 16S rRNA Chinese medicine |
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