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急性低氧对大鼠胃黏膜组织细胞端粒长度的影响及其机制

王亚平, 朱智勇, 唐颖, 马颖才

青海省人民医院消化内科，西宁 810007

摘要

本文旨在观察急性低氧对大鼠胃黏膜组织细胞端粒长度的影响，并探讨其机制。40只雄性Wistar大鼠，随机分为对照组(兰州，1 500 m，n = 10)与实验组(低压氧舱，5 000 m)，实验组根据低氧暴露时间不同，又分为低氧1、3、7 d三组，每组各10只。低氧暴露完毕，取各组大鼠胃组织，行HE染色观察胃黏膜组织显微形态变化；采用real-time PCR法测胃黏膜组织细胞端粒长度；采用real-time PCR及ELISA法分别检测端粒酶逆转录酶(telomerase reverse transcriptase, TERT)、低氧诱导因子1α (hypoxia-inducible factor 1α, HIF-1α)、HIF-2α mRNA及蛋白表达水平；采用化学荧光法检测其活性氧(reactive oxygen species, ROS)水平；并分析TERT表达水平与HIF-1α、HIF-2α表达水平及端粒长度的相关性。结果显示，随着低氧时间的延长，胃黏膜组织细胞损伤逐渐加重，ROS生成量逐渐升高，端粒长度逐渐增加，TERT和HIF-1α mRNA及蛋白表达水平的变化趋势与端粒长度的变化趋势一致，而HIF-2α表达水平未见明显变化，仅在低氧7 d时表达增加；TERT mRNA表达水平与端粒长度之间、TERT mRNA和蛋白表达水平与HIF-1α之间均存在正相关性，而TERT mRNA表达水平与HIF-2α之间无明显相关性。上述结果提示，急性高原严重低氧环境下，机体产生大量ROS，损伤胃黏膜组织细胞，同时又通过HIF-1α上调TERT的表达及端粒酶活性，增加细胞端粒长度，使胃黏膜组织细胞产生适应性反应，避免发生严重损伤。

关键词： 低氧; 端粒 ; 端粒酶逆转录酶 ; 低氧诱导因子 ; 活性氧自由基

分类号：R339.5

Effects of acute hypoxia on telomere length of rat gastric mucosa tissue and underlying mechanism

WANG Ya-Ping, ZHU Zhi-Yong, TANG Ying, MA Ying-Cai

Digestive Department of Qinghai Provincial People’s Hospital, Xining 810007, China

Abstract

The present study was aimed to investigate the effect of acute hypoxia on telomere length of rat gastric mucosa tissue and possible mechanism. Forty male Wistar rats were randomly divided into control group (resided in Lanzhou, 1 500 m) and experimental group (hypoxia chamber, 5 000 m). The experimental group was further divided into 3 subgroups and exposed to hypoxia for 1, 3, 7 d (n = 10), respectively. The morphological changes of the gastric mucosa tissue were observed by HE staining. By means of real-time PCR, ELISA and chemical immunofluorescence methods, the telomere length, the mRNA and protein levels of telomerase reverse transcriptase (TERT), hypoxia-inducible factor 1α (HIF-1α) and HIF-2α, and reactive oxygen species (ROS) level in gastric mucosa tissue were measured, respectively. The results showed that, with the extension of hypoxia-exposure time, the injury in gastric mucosa cells progressively became worse, and telomere length was increased gradually, along with intracellular ROS generation. The changes of TERT and HIF-1α expressions induced by acute hypoxia were in the same trend as that of telomere length. There were positive correlations between TERT mRNA expression and telomere length and between TERT and HIF-1α expressions, but not between TERT and HIF-2α mRNA expressions. These results suggest that under acute severe hypoxia environment, ROS could damage the gastric mucosa tissue cells, meanwhile the expressions of TERT and telomerase activity may be up-regulated by HIF-1α, which can elongate the telomere length and protect gastric mucosa tissue against fatal injury.

Key words: Hypoxia; telomere ; telomerase reverse transcriptase ; hypoxia-inducible factor ; reactive oxygen species

收稿日期：2017-03-25　　录用日期：2017-05-08

通讯作者：王亚平　　E-mail: rose19820721@126.com

引用本文：

王亚平, 朱智勇, 唐颖, 马颖才. 急性低氧对大鼠胃黏膜组织细胞端粒长度的影响及其机制[J]. 生理学报 2017; 69 (4): 429-436.

WANG Ya-Ping, ZHU Zhi-Yong, TANG Ying, MA Ying-Cai. Effects of acute hypoxia on telomere length of rat gastric mucosa tissue and underlying mechanism. Acta Physiol Sin 2017; 69 (4): 429-436 (in Chinese with English abstract).