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参术调脾颗粒对肠道微生物群和代谢物的改变可减轻GK大鼠的高血糖。

Alterations of the gut microbiota and metabolites by ShenZhu TiaoPi granule alleviates hyperglycemia in GK rats.

作者信息

Zhao Jindong, Fang Zhaohui

机构信息

Department of Endocrinology, The First Affiliated Hospital of Anhui University of Chinese Medicine, Hefei, Anhui, China.

Center for Xin'an Medicine and Modernizatison of Traditional Chinese Medicine of IHM, The First Affiliated Hospital of Anhui University of Chinese Medicine, Hefei, Anhui, China.

出版信息

Front Microbiol. 2024 Aug 29;15:1420103. doi: 10.3389/fmicb.2024.1420103. eCollection 2024.

Abstract

ShenZhu TiaoPi granule (STG) is a compound prescription that is used in Chinese medicine for the treatment of type 2 diabetes mellitus (T2DM). Previous studies have indicated a hypoglycaemic effect, but the underlying mechanism remains unclear. Goto-Kakizaki (GK) rats were used to establish an in vivo T2DM model (Mod). The metformin (Met) and STG treatment time was 12 weeks. Fasting blood glucose (FBG) and insulin levels and the area under the glucose curve (GAUC) were measured. Intestinal pathology and permeability were observed. Microbial diversity analysis and metabolomics were used to investigate the underlying mechanisms. Compared with the Con group, the T2DM Mod group presented significant differences in weight, FBG, GAUC, and homeostasis model assessment-insulin resistance (HOMA-IR) indices ( < 0.01). Met and STG improved these indicators ( < 0.01). The pathological morphology and zonula occludens 1 protein levels in the intestines of the Mod group of rats were altered, leading to increases in the lipopolysaccharide (LPS) and interleukin-1β (IL-1β) levels. In the Met and STG groups, the intestinal conditions improved, and the LPS and IL-1β levels significantly decreased ( < 0.01). Changes in the gut microbiota and metabolites occurred in the Mod group. In the STG group, the abundance of Intestinimonas increased, and the abundance of Eubacterium coprostanoligenes decreased significantly ( < 0.05). Moreover, STG also altered 2-deoxyglucose, beta-muricholic acid and dioxolithocholic acid production. In addition, the main metabolic pathways affected by STG were bile acid biosynthesis and cholesterol metabolism. Intestinimonas, D-maltose_and_alpha-lactose may be potential biomarkers for the effects of STG. STG alleviates hyperglycaemia via the gut microbiota and metabolites in GK rats.

摘要

参术调脾颗粒(STG)是一种用于治疗2型糖尿病(T2DM)的中药复方制剂。先前的研究表明其具有降血糖作用,但其潜在机制尚不清楚。采用自发性2型糖尿病GK大鼠建立体内T2DM模型(Mod)。二甲双胍(Met)和STG的治疗时间为12周。测定空腹血糖(FBG)、胰岛素水平及葡萄糖曲线下面积(GAUC)。观察肠道病理及通透性。采用微生物多样性分析和代谢组学研究其潜在机制。与对照组相比,T2DM Mod组在体重、FBG、GAUC和稳态模型评估胰岛素抵抗(HOMA-IR)指数方面存在显著差异(<0.01)。Met和STG改善了这些指标(<0.01)。Mod组大鼠肠道的病理形态和紧密连接蛋白1水平发生改变,导致脂多糖(LPS)和白细胞介素-1β(IL-1β)水平升高。在Met和STG组中,肠道状况改善,LPS和IL-1β水平显著降低(<0.01)。Mod组肠道微生物群和代谢产物发生了变化。在STG组中,肠单胞菌的丰度增加,产粪甾醇真杆菌的丰度显著降低(<0.05)。此外,STG还改变了2-脱氧葡萄糖、β-鼠胆酸和二氧石胆酸的产生。此外,受STG影响主要的代谢途径是胆汁酸生物合成和胆固醇代谢。肠单胞菌、D-麦芽糖和α-乳糖可能是STG作用的潜在生物标志物。STG通过GK大鼠的肠道微生物群和代谢产物减轻高血糖。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3178/11451479/9fb48e718be0/fmicb-15-1420103-g001.jpg

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