Protective effects of L-arginine on the intestinal epithelial barrier under heat stress conditions in rats and IEC-6 cell line
Protective effects of L-arginine on the intestinal epithelial barrier under heat stress conditions in rats and IEC-6 cell line
复制标题
L-精氨酸对热应激条件下大鼠和IEC-6细胞系肠上皮屏障的保护作用
DOI：
10.1111/jpn.13246
复制
发表时间：
2019-11-11
影响因子：
2.7
通讯作者：
Xia, Zhaofei
中科院分区：
文献类型：
--
作者：
Huang, Liqing;Yin, Peng;Xia, Zhaofei
热应激（HS）和相关的限制血液流向肠道已被证明会破坏肠道的完整性。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增加响应HS。HS条件下，肠组织损伤表现出明显的形态学改变。此外，HS降低了Nurr 1、ZO-1、occludin、claudin-6和E-cadherin的mRNA和蛋白表达水平，增加了NF-κ B B和IL-1 β的mRNA表达，并增加了切割的caspase-3的蛋白表达。与此相反，L-精氨酸补充剂保持肠道完整性，增加绒毛/隐窝比。L-精氨酸还抑制炎症相关基因的表达和切割的caspase-3的蛋白表达，而它上调紧密连接蛋白和LC 3B蛋白表达的mRNA和蛋白表达。在体外，L-精氨酸衰减HS诱导的细胞凋亡，通过流式细胞术和减少裂解的caspase-3蛋白表达。L-精氨酸诱导自噬，表现为p62和p-mTOR/mTOR表达降低，LC 3B表达增加。在IEC-6细胞中，TJ蛋白的蛋白表达水平也被L-精氨酸增强。总而言之，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HS条件下的自噬来减轻肠道损伤并保护肠道完整性。
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-kappa B and IL-1 beta, 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.