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L-精氨酸在热应激条件下对大鼠和 IEC-6 细胞系肠上皮屏障的保护作用。

Protective effects of L-arginine on the intestinal epithelial barrier under heat stress conditions in rats and IEC-6 cell line.

机构信息

College of Veterinary Medicine, China Agricultural University, Beijing, China.

Institute of Microbiology, Chinese Academy of Sciences, Beijing, China.

出版信息

J Anim Physiol Anim Nutr (Berl). 2020 Jan;104(1):385-396. doi: 10.1111/jpn.13246. Epub 2019 Nov 11.

Abstract

Heat stress (HS) and the associated restricted blood flow to the intestine have been proven to destroy intestinal integrity. Considering the beneficial properties of L-arginine on gut function, we investigated the protective effects of L-arginine on the intestine under HS conditions. In vivo, the serum cortisol level and the rectal temperature increased in response to HS. Under HS, the intestinal damage showed obvious morphological changes. Furthermore, HS decreased the mRNA and protein expression levels of Nurr1, ZO-1, occludin, claudin-6 and E-cadherin, increased the mRNA expression of NF-κB and IL-1β, and increased the protein expression of cleaved caspase-3. In contrast, L-arginine supplementation maintained intestinal integrity and increased the villus/crypt ratio. L-arginine also suppressed the expression of inflammation-related genes and the protein expression of cleaved caspase-3, whereas it upregulated the mRNA and protein expression of tight junction proteins and LC3B protein expression. In vitro, L-arginine attenuated HS-induced apoptosis as demonstrated by flow cytometry and decreased cleaved caspase-3 protein expression. L-arginine induced autophagy, which was demonstrated by decreased expression of p62 and p-mTOR/mTOR, and increased expression of LC3B. The protein expression levels of TJ proteins also enhanced by L-arginine in IEC-6 cells. Taken together, these results suggest that L-arginine can alleviate intestinal damage and protect the intestinal integrity by suppressing local inflammation response, promoting the production of TJs and facilitating autophagy under HS conditions.

摘要

热应激(HS)和相关的肠道血流受限已被证明会破坏肠道完整性。考虑到 L-精氨酸对肠道功能的有益特性,我们研究了 L-精氨酸在 HS 条件下对肠道的保护作用。在体内,血清皮质醇水平和直肠温度升高是对 HS 的反应。在 HS 下,肠道损伤表现出明显的形态变化。此外,HS 降低了 Nurr1、ZO-1、occludin、claudin-6 和 E-cadherin 的 mRNA 和蛋白表达水平,增加了 NF-κB 和 IL-1β 的 mRNA 表达,并增加了 cleaved caspase-3 的蛋白表达。相比之下,L-精氨酸补充剂维持了肠道完整性,增加了绒毛/隐窝比。L-精氨酸还抑制了炎症相关基因的表达和 cleaved caspase-3 的蛋白表达,同时上调了紧密连接蛋白的 mRNA 和蛋白表达以及 LC3B 蛋白表达。在体外,L-精氨酸通过流式细胞术减轻了 HS 诱导的细胞凋亡,并降低了 cleaved caspase-3 蛋白的表达。L-精氨酸诱导了自噬,这表现为 p62 和 p-mTOR/mTOR 的表达减少以及 LC3B 的表达增加。L-精氨酸还增强了 IEC-6 细胞中 TJ 蛋白的蛋白表达水平。总之,这些结果表明,L-精氨酸可以通过抑制局部炎症反应、促进 TJ 的产生和促进自噬来减轻肠道损伤并保护肠道完整性。

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