基于肠道产丁酸菌代谢探讨益糖康防治2型糖尿病的作用机制  

Mechanism of Yitangkang(益糖康)in Treatment of Type 2 Diabetes Mellitus Based on Metabolism of Intestinal Butyric-Producing Bacteria

作　　者：韩雪莹 单国顺[1] 窦德强[1] 于嘉祥 张瀚文[1] 杨宇峰[1] 石岩[1] HAN Xueying;SHAN Guoshun;DOU Deqiang;YU Jiaxiang;ZHANG Hanwen;YANG Yufeng;SHI Yan(Liaoning University of Traditional Chinese Medicine,Shenyang 110847,Liaoning,China)

机构地区：[1]辽宁中医药大学,辽宁沈阳110847

出　　处：《中华中医药学刊》2023年第3期46-51,共6页Chinese Archives of Traditional Chinese Medicine

基　　金：国家自然科学基金青年科学基金项目(81803726);中国博士后科学基金面上项目(2021M693852);辽宁省科技厅博士科研启动课题(2021-BS-183);辽宁省教育厅基本科研项目(LJKQZ20222385);辽宁中医药大学中医脏象理论及应用国家教育部重点实验室开放基金项目(zyzx2109);辽宁中医药大学博士后启动基金项目(21601A2011);辽宁中医药大学科研项目(2021LZY045)。

摘　　要：目的基于肠道产丁酸菌代谢探讨益糖康改善慢性炎症防治2型糖尿病(type 2 diabetes mellitus,T2DM)的作用机制。方法采用高脂饲料喂养结合一次性腹腔注射链脲佐菌素45 mg/kg制备2型糖尿病大鼠模型。将造模成功的24只SD大鼠随机分为模型组、益糖康组、二甲双胍组,每组8只,另设普通饲料喂养的SD大鼠8只为空白组。益糖康组给予益糖康生药56 g/(kg·d)灌胃,二甲双胍组给予盐酸二甲双胍片150 mg/(kg·d)灌胃,空白组、模型组给予0.1 mL/10 g生理盐水灌胃,各组均每日1次。灌胃4周后,测定大鼠血糖,按照试剂盒测定大鼠血清中肿瘤坏死因子-α(tumor necrosis factor-α,TNF-α)、单核细胞趋化蛋白1(monocyte chemoattractant protein-1,MCP-1)水平。GC-MS测定粪便中丁酸含量;16S rRNA测序分析粪便中产丁酸菌丰度变化。结果益糖康能显著降低大鼠血糖(P<0.05)及血清中TNF-α、MCP-1水平(P<0.01),增加粪便中丁酸含量(P<0.01)。研究中厚壁菌门(Firmicutes)与丁酸含量正相关,益糖康组可明显增加厚壁菌门丰度(P<0.05);在属水平上,norank_f_norank_o_Clostridia_UCG-014、Ruminococcus、Prevotella、Colidextribacter、Faecalibacterium、norank_f_Lachnospiraceae与丁酸正相关,益糖康组norank_f_Lachnospiraceae含量显著升高(P<0.05)。结论益糖康能够增加产丁酸菌Firmicutes门及norank_f_Lachnospiraceae菌属丰度,可以显著增加粪便中丁酸含量,缓解T2DM大鼠全身慢性炎症水平,降低血糖,防治2型糖尿病。Objective To explore the mechanism of Yitangkang(益糖康)in the prevention of type 2 diabetes mellitus(T2DM)via butyrate-producing bacteria and its metabolites butyric acid and chronic inflammation.Methods The model of T2DM was established by high-fat diet and one-time intraperitoneal injection of streptozotocin(STZ,45 mg/kg).The successfully-modeled 24 SD rats were randomly divided into model group,Yitangkang group and metformin group,with 8 rats in each group,while 8 SD rats with ordinary diet were also set as the blank group.The Yitangkang group was given 56 g/(kg·d)of crude Yitangkang by gavage.The metformin group was given 150 mg/(kg·d)of metformin hydrochloride tablets by gavage.The blank group and model group were given 0.1 mL/10 g of normal saline by gavage,once a day in all groups.After 4 weeks,the levels of blood glucose,tumor necrosis factor-α(TNF-α)and monocyte chemoattractant protein 1(MCP-1)were measured.GC-MS was used to determine butyric acid in feces samples,and 16S rRNA technology was used to determine the abundance of butyric-producing bacteria of feces samples.Results Yitangkang could significantly decrease blood glucose(P<0.05),the levels of TNF-αand MCP-1(P<0.01),and increased fecal butyric acid content(P<0.01).In this study,Firmicutes was positively correlated with butyric acid,and the abundance of Firmicutes in Yitangkang group was significantly increased(P<0.05).At the genus level,norank_f_norank_o_Clostridia_UCG-014,Ruminococcus,Prevotella,Colidextribacter,Faecalibacterium and norank_f_Lachnospiraceae were positively correlated with butyric acid.The content of norank_f_Lachnospiraceae in Yitangkang group was significantly increased(P<0.05).Conclusion Yitangkang increased the abundances of Firmicutes and norank_f_Lachnospiraceae,which were the butyrate-producing bacteria in the study.Yitangkang could significantly increase the content of butyric acid in feces,alleviate systemic chronic inflammation,reduce the blood glucose and prevent T2DM.

关 键 词：2型糖尿病 益糖康 产丁酸菌 慢性炎症 丁酸 

分 类 号：R285.5[医药卫生—中药学]