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四君子汤对2型糖尿病小鼠肠道屏障的影响

[Effect of Sijunzi Decoction on intestinal barrier of type 2 diabetic mice].

作者信息

Li Hui, Xie Jin-Zhu, Fan Ruo-Xi, Yang Li, Zhou Qiu-Yue, Zhou Ning-Na

机构信息

School of Chinese Materia Medica & Yunnan Key Laboratory of Southern Medicine Utilization, Yunnan University of Chinese Medicine Kunming 650500, China.

Yunnan Medical and Health Career College Kunming 650106, China.

出版信息

Zhongguo Zhong Yao Za Zhi. 2024 Aug;49(16):4510-4520. doi: 10.19540/j.cnki.cjcmm.20240429.401.

Abstract

This study aims to explore the improvement effect of Sijunzi Decoction on intestinal barrier in diabetic mice. A type 2 diabetes mellitus(T2DM) model was established in C57BL/6J mice by feeding them with high-sugar and high-fat diet combined with streptozotocin(STZ). The T2DM mice were randomly divided into a control group, a T2DM group, a donepezil(DON) group, a rosiglitazone(RGZ) group, and Sijunzi Decoction groups(7. 5, 15, and 30 g·kg(-1)), and orally administered for six weeks. The body weight and fasting plasma glucose(FBG) of mice were recorded. Fasting plasma insulin(FINS) and insulin resistance index(HOMA-IR) were observed to assess insulin resistance(IR). Intestinal flora and levels of serotonin(5-HT), lipopolysaccharide(LPS), and short-chain fatty acids(SCFAs) in serum were analyzed. Changes in colonic structure and tight junction proteins occludin, claudin-1,and ZO-1 were observed through HE staining and immunohistochemistry. Spontaneous alternation test was conducted to observe the effect on spatial memory ability. Compared with the results in the control group, FBG and HOMA-IR in the T2DM group were significantly increased(P< 0. 01); species richness index(Sobs index), Shannon diversity index(Shannon index), and species abundance estimate index(Chao index) were decreased; LPS was significantly increased(P< 0. 001), while the levels of 5-HT,SCFAs, occludin, claudin-1, and ZO-1 were significantly decreased(P< 0. 01), indicating impaired colonic barrier function;spontaneous alternation accuracy was significantly decreased(P<0. 05). After 6 weeks of Sijunzi Decoction treatment, compared with the results in the T2DM group, FBG and HOMA-IR in the Sijunzi Decoction 15 g·kg(-1) group were significantly decreased(P<0. 01);Sobs index, Shannon index, and Chao index were increased; LPS was significantly decreased(P<0. 01), while the levels of 5-HT,SCFAs, occludin, claudin-1, and ZO-1 were significantly increased(P< 0. 05), indicating improved colonic barrier function;spontaneous alternation accuracy was increased(P<0. 001). In conclusion, Sijunzi Decoction has the effect of improving intestinal barrier in diabetic mice.

摘要

本研究旨在探讨四君子汤对糖尿病小鼠肠道屏障的改善作用。通过给C57BL/6J小鼠喂食高糖高脂饮食并联合链脲佐菌素(STZ)建立2型糖尿病(T2DM)模型。将T2DM小鼠随机分为对照组、T2DM组、多奈哌齐(DON)组、罗格列酮(RGZ)组和四君子汤组(7.5、15和30 g·kg⁻¹),并进行六周的口服给药。记录小鼠的体重和空腹血糖(FBG)。观察空腹血浆胰岛素(FINS)和胰岛素抵抗指数(HOMA-IR)以评估胰岛素抵抗(IR)。分析肠道菌群以及血清中血清素(5-HT)、脂多糖(LPS)和短链脂肪酸(SCFAs)的水平。通过HE染色和免疫组织化学观察结肠结构以及紧密连接蛋白闭合蛋白、闭合蛋白-1和闭锁小带蛋白-1的变化。进行自发交替试验以观察对空间记忆能力的影响。与对照组结果相比,T2DM组的FBG和HOMA-IR显著升高(P<0.01);物种丰富度指数(Sobs指数)、香农多样性指数(Shannon指数)和物种丰度估计指数(Chao指数)降低;LPS显著升高(P<0.001),而5-HT、SCFAs、闭合蛋白、闭合蛋白-1和闭锁小带蛋白-1的水平显著降低(P<0.01),表明结肠屏障功能受损;自发交替准确性显著降低(P<0.05)。四君子汤治疗6周后,与T2DM组结果相比,四君子汤15 g·kg⁻¹组的FBG和HOMA-IR显著降低(P<0.01);Sobs指数、Shannon指数和Chao指数升高;LPS显著降低(P<0.01),而5-HT、SCFAs、闭合蛋白、闭合蛋白-1和闭锁小带蛋白-1的水平显著升高(P<0.05),表明结肠屏障功能改善;自发交替准确性升高(P<0.001)。综上所述,四君子汤具有改善糖尿病小鼠肠道屏障的作用。

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