摘要
目的:研究参苓固肠方通过调节肠道菌群及其产物短链脂肪酸干预妊娠期糖尿病大鼠血糖的作用机制。方法:从受孕成功的36只孕鼠中随机选取30只孕鼠进行造模。造模大鼠予以高脂高糖饲料喂养1周后,连续3 d予以35 mg·kg^(-1)链脲佐菌素(STZ)构建妊娠期糖尿病模型,造模成功后随机分为模型组、二甲双胍组、参苓固肠方高、中、低剂量组,分别予以18、9、4.5 mg·kg^(-1)的参苓固肠方溶液灌胃,二甲双胍组予以52.5 mg·kg^(-1)药物溶液灌胃,空白组、模型组予以等体积生理盐水灌胃。末次给药24 h后,鼠尾尖采血检测末次血糖,麻醉下腹主动脉采血,生化法测甘油三酯(TG)、总胆固醇(TC)、高密度脂蛋白胆固醇(HDL-C)和低密度脂蛋白胆固醇(LDL-C)水平,酶联免疫吸附测定法(ELISA)检测脂多糖(LPS)、白细胞介素-1β(IL-1β)、白细胞介素-6(IL-6)、肿瘤坏死因子-α(TNF-α)、胰岛素(INS);取大鼠肠道组织,苏木素-伊红(HE)染色法观察肠道组织病理变化;取大鼠粪便标本,16s rRNA测序检测肠道菌群,气相色谱法检测短链脂肪酸。结果:与空白组比较,模型组大鼠不良妊娠结局发生率明显升高(P<0.05),与模型组比较,参苓固肠方各剂量组及二甲双胍组不良妊娠结局发生率明显降低(P<0.05);与空白组比较,模型组血糖、TG、TC、HDL-C、LDL-C、LPS、IL-1β、IL-6、TNF-α水平明显升高(P<0.05),肠道组织均有不同程度的炎性改变及黏膜损伤,与模型组比较,参苓固肠方各剂量组及二甲双胍组血糖、TG、TC、HDL-C、LDL-C、LPS、IL-1β、IL-6、TNF-α等水平有所下调(P<0.05),肠道炎症及肠黏膜损伤得到改善;与空白组比较,模型组肠道菌群功能结构及多样性发生改变(P<0.05),与模型组比较,参苓固肠方各剂量组及二甲双胍组肠道菌群功能结构及多样性回调,趋势接近空白组(P<0.05);与空白组比较,模型组大鼠大肠埃希菌、肠球菌、克雷伯氏杆菌�
Objective:To study the mechanism of Shenling Guchang prescription on blood glucose of gestational diabetes mellitus rats by regulating intestinal flora and short chain fatty acids.Method:The30 pregnant rats were randomly selected from 36 pregnant rats which were successfully pregnant.The model rats were fed with high-fat and high-sugar diet for 1 week,and 35 mg·kg^(-1)streptozotocin(STZ)was given for3 consecutive days to construct a gestational diabetes model.After successful modeling,the rats were randomly divided into model group,metformin group,Shenling Guchang prescription low-,medium-and high-dose group.The high dose group of Shenling Guchang prescription was given 18 mg·kg^(-1),the middle dose group was given 9 mg·kg^(-1),the low dose group was given 4.5 mg·kg^(-1)drug solution by gavage,the metformin group was given 52.5 mg·kg^(-1)drug solution by gavage,the blank group and the model group were given equal volume of normal saline by gavage.At 24 h after the last administration,blood samples were collected from the tail tip of the rats to measure the blood glucose,and blood samples were collected from the abdominal aorta under anesthesia to measure the levels of triglyceride(TG),total cholesterol(TC),high density lipoprotein cholesterol(HDL-C)and low density lipoprotein cholesterol(LDL-C).Lipopolysaccharides(LPS),interleukin-1β(IL-1β),interleukin-6(IL-6),tumor necrosis factor-α(TNF-α)and insulin(INS)were detected by enzyme-linked immunosorbent assay(ELISA).The intestinal tissue of rats was taken,and the pathological changes of intestinal tissue were observed by hematoxylin-eosin(HE)staining.Fecal samples were collected from rats,16S rRNA sequencing was used to detect intestinal flora,and short-chain fatty acids were detected by gas chromatography.Result:Compared with the blank group,the incidence of adverse pregnancy outcomes in the model group was significantly increased(P<0.05).Compared with the model group,the incidence of adverse pregnancy outcomes in the Shenling Guchang prescription groups an
作者
周相宇
周素芳
何江艳
高镜云
华诏召
ZHOU Xiang-yu;ZHOU Su-fang;HE Jiang-yan;GAO Jing-yun;HUA Zhao-zhao(Guizhou University of Traditional Chinese Medicine,Guizhou,Guiyang,550002;First Affiliated Hospital of Guizhou University of Traditional Chinese Medicine,Guizhou,Guiyang,550001;Second Affiliated Hospital of Guizhou University of Traditional Chinese Medicine,Guizhou,Guiyang,550000)
出处
《中国实验方剂学杂志》
CAS
CSCD
北大核心
2022年第23期53-63,共11页
Chinese Journal of Experimental Traditional Medical Formulae
基金
国家自然科学基金项目(81460683)
贵州省中医药科学技术研究专项课题(QZYY-2021-120)。
关键词
参苓固肠方
妊娠期糖尿病
肠道菌群
血糖
血脂
短链脂肪酸
炎症因子
Shenling Guchang prescription
gestational diabetes
intestinal flora
blood glucose
blood lipid
short-chain fatty acids
inflammatory factors
