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有氧运动通过 TLR4/MyD88/NF-κB 信号通路改善糖尿病大鼠的肠道黏膜屏障功能障碍。

Aerobic exercise improves intestinal mucosal barrier dysfunction through TLR4/MyD88/NF-κB signaling pathway in diabetic rats.

机构信息

Key Laboratory of Physical Fitness and Exercise Rehabilitation of Hunan Province, College of Physical Education, Hunan Normal University, Changsha, China.

出版信息

Biochem Biophys Res Commun. 2022 Dec 17;634:75-82. doi: 10.1016/j.bbrc.2022.09.075. Epub 2022 Sep 22.

Abstract

This study examined the effects of aerobic exercise on the intestinal mucosal barrier dysfunction in diabetic rats. We established a diabetic rats model consisting of three groups: normal control (NC), diabetes control (DC), and diabetes eight-week aerobic exercise (DE). We measured serum fasting blood glucose (FBG), insulin (INS), diamine oxidase (DAO), D(-)-lactate (D-Lac), lipopolysaccharide (LPS), tumour necrosis factor-α (TNF-α), interleukin-6 (IL-6), and insulin resistance index (HOMA-IR). Intestinal sections of tissue were stained with H&E and examined using transmission electron microscopy. Expressions of occludin, claudin-1, toll-like receptor-4 (TLR4), myeloid differentiation primary response protein 88 (MyD88), and nuclear factor-κB (NF-κB) in small intestinal mucosa were determined by Western Blot. In comparison to NC, FBG, HOMA-IR, DAO, D-Lac, TNF-α, IL-6, and LPS were increased (P < 0.05) in DC, whereas INS, villus height, crypt depth, and mucosal thickness were decreased (P < 0.05). In comparison to DC, FBG, DAO, D-Lac, TNF-α, and LPS were decreased (P < 0.05) in DE, whereas INS, villus height, crypt depth, and mucosal thickness were increased (P < 0.05). In comparison to NC, occludin and claudin-1 were decreased (P < 0.05) in DC, whereas TLR4, MyD88, and NF-κB were increased (P < 0.05). In comparison to DC, occludin and claudin-1 were increased (P < 0.05) in DE, whereas TLR4, MyD88, and NF-κB were decreased (P < 0.05). In conclusion, eight-week aerobic exercise improved intestinal mucosal barrier dysfunction in diabetic rats, by inhibiting LPS release, TLR4/MyD88/NF-κB signaling pathway, and pro-inflammatory cytokines expression.

摘要

本研究探讨了有氧运动对糖尿病大鼠肠黏膜屏障功能障碍的影响。我们建立了一个糖尿病大鼠模型,包括三个组:正常对照组(NC)、糖尿病对照组(DC)和糖尿病八周有氧运动组(DE)。我们测量了血清空腹血糖(FBG)、胰岛素(INS)、二胺氧化酶(DAO)、D(-)-乳酸(D-Lac)、脂多糖(LPS)、肿瘤坏死因子-α(TNF-α)、白细胞介素-6(IL-6)和胰岛素抵抗指数(HOMA-IR)。用 H&E 染色肠道组织切片,并通过透射电子显微镜进行检查。用 Western Blot 测定小肠黏膜中闭合蛋白、闭合蛋白-1、Toll 样受体 4(TLR4)、髓样分化初级反应蛋白 88(MyD88)和核因子-κB(NF-κB)的表达。与 NC 相比,DC 组的 FBG、HOMA-IR、DAO、D-Lac、TNF-α、IL-6 和 LPS 均升高(P<0.05),而 INS、绒毛高度、隐窝深度和黏膜厚度均降低(P<0.05)。与 DC 相比,DE 组的 FBG、DAO、D-Lac、TNF-α和 LPS 均降低(P<0.05),而 INS、绒毛高度、隐窝深度和黏膜厚度均升高(P<0.05)。与 NC 相比,DC 组的闭合蛋白和闭合蛋白-1 降低(P<0.05),而 TLR4、MyD88 和 NF-κB 升高(P<0.05)。与 DC 相比,DE 组的闭合蛋白和闭合蛋白-1 升高(P<0.05),而 TLR4、MyD88 和 NF-κB 降低(P<0.05)。综上所述,八周有氧运动通过抑制 LPS 释放、TLR4/MyD88/NF-κB 信号通路和促炎细胞因子表达,改善了糖尿病大鼠的肠黏膜屏障功能障碍。

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