Resolvins 可通过 HO-1 途径防止糖尿病引起的结肠氧化应激、屏障功能障碍和相关腹泻。

IF 5 3区 生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY
BioFactors Pub Date : 2024-03-14 DOI:10.1002/biof.2049
Ting Yu, Die Chen, Hongyan Qi, Lin Lin, Yurong Tang
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引用次数: 0

摘要

糖尿病与氧化应激增加有关,导致结肠上皮细胞紧密连接形成改变和凋亡增加。这些变化可能导致糖尿病患者肠道屏障功能障碍和相应的胃肠道症状,包括腹泻。本研究旨在阐明 Resolvin D1(RvD1)对糖尿病引起的氧化应激和结肠屏障破坏的影响和机制。用 RvD1 治疗链脲佐菌素诱导的糖尿病小鼠 2 周,然后评估小鼠的大便次数、大便含水量、肠道通透性、结肠跨上皮电阻、活性氧(ROS)的产生、细胞凋亡以及紧密连接蛋白 Zonula Occludens 1 (ZO-1) 和 occludin 的表达。在葡萄糖升高的人结肠培养物中也评估了相同的参数。我们发现,RvD1 处理不会影响血糖,但会使粪便含水量正常化,并防止肠屏障功能障碍、上皮氧化应激和细胞凋亡。RvD1 还能恢复糖尿病小鼠体内 ZO-1 和闭塞素的表达。RvD1 处理增加了 Akt 的磷酸化,同时上皮细胞中血红素加氧酶-1(HO-1)的表达增加了 3.5 倍。RvD1的保护作用被HO-1的竞争性抑制剂ZnPP阻断。在经 RvD1 处理的葡萄糖升高的人结肠培养物中也观察到了类似的结果。总之,糖尿病患者的氧化应激会导致粘膜屏障功能障碍,从而引发糖尿病性腹泻。通过激活细胞内 PI3K/Akt 以及随后上调肠上皮细胞中的 HO-1 来防止 ROS 介导的粘膜损伤并保护肠道屏障功能。这些作用可使糖尿病小鼠的大便次数和大便含水量恢复正常,这表明resolvins可用于治疗糖尿病腹泻。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

Resolvins protect against diabetes-induced colonic oxidative stress, barrier dysfunction, and associated diarrhea via the HO-1 pathway

Resolvins protect against diabetes-induced colonic oxidative stress, barrier dysfunction, and associated diarrhea via the HO-1 pathway

Diabetes is associated with increased oxidative stress, leading to altered tight junction formation and increased apoptosis in colonic epithelial cells. These changes may lead to intestinal barrier dysfunction and corresponding gastrointestinal symptoms in patients with diabetes, including diarrhea. The aim of this study was to characterize the effect and mechanism of Resolvin D1 (RvD1) on diabetes-induced oxidative stress and barrier disruption in the colon. Mice with streptozotocin-induced diabetes were treated with RvD1 for 2 weeks, then evaluated for stool frequency, stool water content, gut permeability, and colonic transepithelial electrical resistance as well as production of reactive oxygen species (ROS), apoptosis, and expression of tight junction proteins Zonula Occludens 1 (ZO-1) and occludin. The same parameters were assessed in human colonoid cultures subjected to elevated glucose. We found that RvD1 treatment did not affect blood glucose, but normalized stool water content and prevented intestinal barrier dysfunction, epithelial oxidative stress, and apoptosis. RvD1 also restored ZO-1 and occludin expression in diabetic mice. RvD1 treatment increased phosphorylation of Akt and was accompanied by a 3.5-fold increase in heme oxygenase-1 (HO-1) expression in the epithelial cells. The protective effects of RvD1 were blocked by ZnPP, a competitive inhibitor of HO-1. Similar findings were observed in RvD1-treated human colonoid cultures subjected to elevated glucose. In conclusion, Oxidative stress in diabetes results in mucosal barrier dysfunction, contributing to the development of diabetic diarrhea. Resolvins prevent ROS-mediated mucosal injury and protect gut barrier function by intracellular PI3K/Akt activation and subsequent HO-1 upregulation in intestinal epithelial cells. These actions result in normalizing stool frequency and stool water content in diabetic mice, suggesting that resolvins may be useful in the treatment of diabetic diarrhea.

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来源期刊
BioFactors
BioFactors 生物-内分泌学与代谢
CiteScore
11.50
自引率
3.30%
发文量
96
审稿时长
6-12 weeks
期刊介绍: BioFactors, a journal of the International Union of Biochemistry and Molecular Biology, is devoted to the rapid publication of highly significant original research articles and reviews in experimental biology in health and disease. The word “biofactors” refers to the many compounds that regulate biological functions. Biological factors comprise many molecules produced or modified by living organisms, and present in many essential systems like the blood, the nervous or immunological systems. A non-exhaustive list of biological factors includes neurotransmitters, cytokines, chemokines, hormones, coagulation factors, transcription factors, signaling molecules, receptor ligands and many more. In the group of biofactors we can accommodate several classical molecules not synthetized in the body such as vitamins, micronutrients or essential trace elements. In keeping with this unified view of biochemistry, BioFactors publishes research dealing with the identification of new substances and the elucidation of their functions at the biophysical, biochemical, cellular and human level as well as studies revealing novel functions of already known biofactors. The journal encourages the submission of studies that use biochemistry, biophysics, cell and molecular biology and/or cell signaling approaches.
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