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牛磺熊去氧胆酸减轻内质网应激并保护肝脏免受慢性间歇性缺氧诱导的损伤。

Tauroursodeoxycholic acid attenuates endoplasmic reticulum stress and protects the liver from chronic intermittent hypoxia induced injury.

作者信息

Hou Yanpeng, Yang Huai'an, Cui Zeshi, Tai Xuhui, Chu Yanling, Guo Xing

机构信息

Department of Otolaryngology, The First Affiliated Hospital of China Medical University, Shenyang, Liaoning 110001, P.R. China.

Department of Otolaryngology, The 463rd Hospital of The Chinese People's Liberation Army, Shenyang, Liaoning 110042, P.R. China.

出版信息

Exp Ther Med. 2017 Sep;14(3):2461-2468. doi: 10.3892/etm.2017.4804. Epub 2017 Jul 19.

Abstract

Obstructive sleep apnea that characterized by chronic intermittent hypoxia (CIH) has been reported to associate with chronic liver injury. Tauroursodeoxycholic acid (TUDCA) exerts liver-protective effects in various liver diseases. The purpose of this study was to test the hypothesis that TUDCA could protect liver against CIH injury. C57BL/6 mice were subjected to intermittent hypoxia for eight weeks and applied with TUDCA by intraperitoneal injection. The effect of TUDCA on liver histological changes, liver function, oxidative stress, inflammatory response, hepatocyte apoptosis and endoplasmic reticulum (ER) stress were investigated. The results showed that administration of TUDCA attenuated liver pathological changes, reduced serum alanine aminotransferase and aspartate aminotransferase level, suppressed reactive oxygen species activity, decreased tumor necrosis factor-α and interleukin-1β level and inhibited hepatocyte apoptosis induced by CIH. TUDCA also inhibited CIH-induced ER stress in liver as evidenced by decreased expression of ER chaperone 78 kDa glucose-related protein, unfolded protein response transducers and ER proapoptotic proteins. Altogether, the present study described a liver-protective effect of TUDCA in CIH mice model, and this effect seems at least partly through the inhibition of ER stress.

摘要

据报道,以慢性间歇性缺氧(CIH)为特征的阻塞性睡眠呼吸暂停与慢性肝损伤有关。牛磺熊去氧胆酸(TUDCA)在各种肝脏疾病中发挥肝脏保护作用。本研究的目的是验证TUDCA可以保护肝脏免受CIH损伤这一假说。将C57BL/6小鼠进行八周的间歇性缺氧处理,并通过腹腔注射给予TUDCA。研究了TUDCA对肝脏组织学变化、肝功能、氧化应激、炎症反应、肝细胞凋亡和内质网(ER)应激的影响。结果表明,给予TUDCA可减轻肝脏病理变化,降低血清丙氨酸氨基转移酶和天冬氨酸氨基转移酶水平,抑制活性氧物质活性,降低肿瘤坏死因子-α和白细胞介素-1β水平,并抑制CIH诱导的肝细胞凋亡。TUDCA还抑制了CIH诱导的肝脏ER应激,这可通过ER伴侣78 kDa葡萄糖相关蛋白、未折叠蛋白反应转导子和ER促凋亡蛋白表达的降低得到证明。总之,本研究描述了TUDCA在CIH小鼠模型中的肝脏保护作用,且这种作用似乎至少部分是通过抑制ER应激实现的。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c12f/5609300/5eded5912562/etm-14-03-2461-g00.jpg

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