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高原应激诱导的肠衰竭大鼠自噬的激活

Activation of autophagy in rats with plateau stress-induced intestinal failure.

作者信息

Zhang Fangxin, Deng Zhiyun, Li Wenxiang, Zheng Xiaofeng, Zhang Jiucong, Deng Shangxin, Chen Jiayu, Ma Qiang, Wang Yong, Yu Xiaohui, Wang Xiufeng

机构信息

Department of Gastroenterology, Lanzhou General Hospital of Lanzhou Military Command Lanzhou 730050, China.

Department of Clinical Laboratory, Lanzhou General Hospital of Lanzhou Military Command Lanzhou 730050, China.

出版信息

Int J Clin Exp Pathol. 2015 Feb 1;8(2):1816-21. eCollection 2015.

Abstract

Hypobaric hypoxia may damage the intestinal mucosa, which may induce multiple organ dysfunction. However, little work has been done regarding whether high altitude hypoxia is associated with failure of the intestinal mucosal barrier. The aim of this study was to investigate the change of the autophagy after the intestinal failure in rats acutely exposed to plateau stress. Fifty Wistar rats were randomly divided into five groups: the plain group, plateau for 6 h, 12 h, 24 h, and 48 h (n = 10 in each group). The acute exposure to plateau was established at a simulated altitude of 4767 meters (m) in a decompression chamber. Intestinal injury was verified by light microscopy. The autophagosomes in the intestinal epithelial cells were observed by transmission electron microscopy (TEM). The protein expression of Beclin1 and LC3B in the intestinal epithelial cells were analyzed by immunohistochemistry. Compared with the plain group, acute exposure to plateau led to a time-dependent damage of the intestinal epithelium. The autophagosome was observed after the intestinal failure following acute exposure to high altitude for 6 h. The expression of Beclin1 and LC3B protein in the rats exposed to acute plateau for 6 h, 12 h, 24 h and 48 h were significantly higher than those in the plain group. The expression of autophagy also showed a significant increase in rats with intestinal failure following acute exposure to plateau stress.

摘要

低压缺氧可能会损害肠黏膜,进而可能诱发多器官功能障碍。然而,关于高原缺氧是否与肠黏膜屏障功能衰竭相关的研究较少。本研究旨在探讨急性暴露于高原应激的大鼠肠功能衰竭后自噬的变化。将50只Wistar大鼠随机分为五组:平原组、高原6小时组、12小时组、24小时组和48小时组(每组n = 10)。在减压舱中模拟海拔4767米建立急性高原暴露模型。通过光学显微镜验证肠道损伤。通过透射电子显微镜(TEM)观察肠上皮细胞中的自噬体。采用免疫组织化学法分析肠上皮细胞中Beclin1和LC3B的蛋白表达。与平原组相比,急性高原暴露导致肠上皮出现时间依赖性损伤。急性高原暴露6小时后肠功能衰竭时观察到自噬体。急性高原暴露6小时、12小时、24小时和48小时的大鼠中Beclin1和LC3B蛋白表达明显高于平原组。急性高原应激后肠功能衰竭的大鼠自噬表达也显著增加。

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