Yisireyili Maimaiti, Wulamu Wubulikasimu, Aili Aikebaier, Li Yiliang, Alimujiang Aziguli, Aipire Aliyeguli, Aizezi Maimaitiaili, Zhang Weimin, Cao Zhengyi, Mijiti Abulajiang, Abudureyimu Kelimu
Research Institute of General and Minimally Invasive Surgery, People's Hospital of Xinjiang Uygur Autonomous Region, Urumqi, Xinjiang 830001, P.R. China.
Department of Minimally Invasive Surgery, Hernia and Abdominal Wall Surgery, People's Hospital of Xinjiang Uygur Autonomous Region, Urumqi, Xinjiang 830001, P.R. China.
Exp Ther Med. 2019 Aug;18(2):1375-1383. doi: 10.3892/etm.2019.7669. Epub 2019 Jun 13.
Although the underlying mechanism of stress remains unknown, it has been associated with the pathophysiology of gastroesophageal reflux diseases, the development of which appear to be accelerated by oxidative stress and fibrosis. The aim of the current study was to investigate the effect of chronic restraint stress on esophageal oxidative stress and fibrosis, as well as the impact of oxidative stress in a murine model whereby 8-week old C57BL/6J male mice were subjected to intermittent chronic restraint stress for a two-week period. The current study demonstrated that chronic restraint stress significantly reduced the body weight of mice compared with the control group. Although chronic restraint stress did not significantly alter the levels of triglycerides or cholesterol, free fatty acid concentration was significantly increased compared with the control group. Furthermore, chronic restraint stress significantly upregulated the expression levels of several fibrotic biomarkers including collagen type I, transforming growth factor β-1, α-smooth muscle actin and SMAD-3 compared with the control group. In addition, the expression levels of the reactive oxygen species (ROS) NADPH oxidase-4 and malondialdehyde were significantly increased, while the expression levels of nuclear factor erythroid 2-related factor 2 and heme oxygenase-1 were significantly decreased in esophageal tissue from mice in the chronic restraint stress group compared with the control group. In conclusion, chronic restraint stress may induce esophageal fibrosis by accumulating ROS and increasing fibrotic gene expression in a murine model.
尽管应激的潜在机制尚不清楚，但它与胃食管反流病的病理生理学有关，胃食管反流病的发展似乎因氧化应激和纤维化而加速。本研究的目的是调查慢性束缚应激对食管氧化应激和纤维化的影响，以及氧化应激在小鼠模型中的作用，在该模型中，8周龄的C57BL/6J雄性小鼠接受了为期两周的间歇性慢性束缚应激。本研究表明，与对照组相比，慢性束缚应激显著降低了小鼠的体重。虽然慢性束缚应激没有显著改变甘油三酯或胆固醇水平，但与对照组相比，游离脂肪酸浓度显著升高。此外，与对照组相比，慢性束缚应激显著上调了几种纤维化生物标志物的表达水平，包括I型胶原、转化生长因子β-1、α-平滑肌肌动蛋白和SMAD-3。此外，与对照组相比，慢性束缚应激组小鼠食管组织中活性氧（ROS）烟酰胺腺嘌呤二核苷酸磷酸氧化酶-4和丙二醛的表达水平显著升高，而核因子红细胞2相关因子2和血红素加氧酶-1的表达水平显著降低。总之，在小鼠模型中，慢性束缚应激可能通过积累ROS和增加纤维化基因表达来诱导食管纤维化。
