Berberine Attenuates Intestinal Mucosal Barrier Dysfunction in Type 2 Diabetic Rats.

Berberine Attenuates Intestinal Mucosal Barrier Dysfunction in Type 2 Diabetic Rats.
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小檗碱减轻 2 型糖尿病大鼠的肠粘膜屏障功能障碍

DOI:
10.3389/fphar.2017.00042
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发表时间:
2017
影响因子:
5.6
通讯作者:
Lu F
Lu F
中科院分区:
医学2区
文献类型:
--
作者:
Gong J;Hu M;Huang Z;Fang K;Wang D;Chen Q;Li J;Yang D;Zou X;Xu L;Wang K;Dong H;Lu F

文献摘要

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背景:肠黏膜屏障功能障碍在糖尿病(DM)的发生发展中起重要作用。小檗碱(BBR)是一种异喹啉类生物碱,对糖尿病和腹泻均有疗效。本研究旨在探讨BBR的抗糖尿病作用是否与肠黏膜屏障功能有关。方法和结果:采用高糖高脂饲料喂养和链脲佐菌素静脉注射建立2型糖尿病大鼠模型。然后用不同浓度的BBR治疗糖尿病大鼠9周。结果显示,除了高血糖和高脂血症,糖尿病大鼠还具有促炎症肠道变化、肠源性激素改变和肠道通透性增加2.77倍的特征。而BBR可明显逆转糖尿病大鼠的上述变化,表现为改善高糖和甘油三酯水平,减轻肠道免疫系统的炎症改变,减轻肠道屏障损伤。高浓度的BBR治疗还使糖尿病大鼠的肠道通透性降低了27.5%。此外,BBR还可调节糖尿病大鼠肠组织中TLR 4/MyD 88/NF-κB信号通路相关分子的表达。结论:BBR的降血糖作用可能与其改善肠源性激素、减轻肠粘膜机械和免疫屏障损伤有关。
Background: Intestinal mucosal barrier dysfunction plays an important role in the development of diabetes mellitus (DM). Berberine (BBR), a kind of isoquinoline alkaloid, is widely known to be effective for both DM and diarrhea. Here, we explored whether the anti-diabetic effect of BBR was related to the intestine mucosal barrier. Methods and Results: The rat model of T2DM was established by high glucose and fat diet feeding and intravenous injection of streptozocin. Then, those diabetic rats were treated with BBR at different concentrations for 9 weeks. The results showed, in addition to hyperglycemia and hyperlipidemia, diabetic rats were also characterized by proinflammatory intestinal changes, altered gut-derived hormones, and 2.77-fold increase in intestinal permeability. However, the treatment with BBR significantly reversed the above changes in diabetic rats, presenting as the improvement of the high glucose and triglyceride levels, the relief of the inflammatory changes of intestinal immune system, and the attenuation of the intestinal barrier damage. BBR treatment at a high concentration also decreased the intestinal permeability by 27.5% in diabetic rats. Furthermore, BBR regulated the expressions of the molecules involved in TLR4/MyD88/NF-κB signaling pathways in intestinal tissue of diabetic rats. Conclusion: The hypoglycemic effects of BBR might be related to the improvement in gut-derived hormones and the attenuation of intestinal mucosal mechanic and immune barrier damages.