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[急性缺氧对大鼠胃黏膜组织端粒长度的影响及潜在机制]

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

作者信息

Wang Ya-Ping, Zhu Zhi-Yong, Tang Ying, Ma Ying-Cai

机构信息

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

出版信息

Sheng Li Xue Bao. 2017 Aug 25;69(4):429-436.

PMID:28825101
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.

摘要

本研究旨在探讨急性缺氧对大鼠胃黏膜组织端粒长度的影响及其可能机制。将40只雄性Wistar大鼠随机分为对照组(居住在兰州,海拔1500米)和实验组(缺氧舱,海拔5000米)。实验组进一步分为3个亚组,分别缺氧暴露1、3、7天(n = 10)。通过HE染色观察胃黏膜组织的形态学变化。分别采用实时荧光定量PCR、酶联免疫吸附测定法(ELISA)和化学免疫荧光法检测胃黏膜组织中端粒长度、端粒酶逆转录酶(TERT)、缺氧诱导因子1α(HIF-1α)和HIF-2α的mRNA及蛋白水平,以及活性氧(ROS)水平。结果显示,随着缺氧暴露时间延长,胃黏膜细胞损伤逐渐加重,端粒长度逐渐增加,同时细胞内ROS生成增加。急性缺氧诱导的TERT和HIF-1α表达变化与端粒长度变化趋势一致。TERT mRNA表达与端粒长度之间、TERT与HIF-1α表达之间呈正相关,但TERT与HIF-2α mRNA表达之间无相关性。这些结果表明,在急性重度缺氧环境下,ROS可损伤胃黏膜组织细胞,同时HIF-1α可能上调TERT的表达及端粒酶活性,从而延长端粒长度,保护胃黏膜组织免受致命损伤。

相似文献

1
[Effects of acute hypoxia on telomere length of rat gastric mucosa tissue and underlying mechanism].[急性缺氧对大鼠胃黏膜组织端粒长度的影响及潜在机制]
Sheng Li Xue Bao. 2017 Aug 25;69(4):429-436.
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Telomere elongation protects heart and lung tissue cells from fatal damage in rats exposed to severe hypoxia.端粒延长可保护暴露于严重缺氧环境下的大鼠心脏和肺组织细胞免受致命损伤。
J Physiol Anthropol. 2018 Feb 17;37(1):5. doi: 10.1186/s40101-018-0165-y.
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Gastric epithelial reactive oxygen species prevent normoxic degradation of hypoxia-inducible factor-1alpha in gastric cancer cells.胃上皮活性氧可防止胃癌细胞中缺氧诱导因子-1α的常氧降解。
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The Apoptotic Effect of HIF-1α Inhibition Combined with Glucose plus Insulin Treatment on Gastric Cancer under Hypoxic Conditions.缺氧条件下HIF-1α抑制联合葡萄糖加胰岛素治疗对胃癌的凋亡作用
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引用本文的文献

1
The HIF-1α as a Potent Inducer of the Hallmarks in Gastric Cancer.缺氧诱导因子-1α作为胃癌特征的强效诱导剂。
Cancers (Basel). 2022 May 30;14(11):2711. doi: 10.3390/cancers14112711.
2
Telomere elongation protects heart and lung tissue cells from fatal damage in rats exposed to severe hypoxia.端粒延长可保护暴露于严重缺氧环境下的大鼠心脏和肺组织细胞免受致命损伤。
J Physiol Anthropol. 2018 Feb 17;37(1):5. doi: 10.1186/s40101-018-0165-y.