發(fā)布時(shí)間：2018-10-24 06:53

【摘要】：本文旨在觀察急性低氧對(duì)大鼠胃黏膜組織細(xì)胞端粒長(zhǎng)度的影響,并探討其機(jī)制。40只雄性Wistar大鼠,隨機(jī)分為對(duì)照組(蘭州,1 500 m,n=10)與實(shí)驗(yàn)組(低壓氧艙,5 000 m),實(shí)驗(yàn)組根據(jù)低氧暴露時(shí)間不同,又分為低氧1、3、7 d三組,每組各10只。低氧暴露完畢,取各組大鼠胃組織,行HE染色觀察胃黏膜組織顯微形態(tài)變化;采用real-time PCR法測(cè)胃黏膜組織細(xì)胞端粒長(zhǎng)度;采用real-time PCR及ELISA法分別檢測(cè)端粒酶逆轉(zhuǎn)錄酶(telomerase reverse transcriptase,TERT)、低氧誘導(dǎo)因子1α(hypoxia-inducible factor 1α,HIF-1α)、HIF-2α mRNA及蛋白表達(dá)水平;采用化學(xué)熒光法檢測(cè)其活性氧(reactive oxygen species,ROS)水平;并分析TERT表達(dá)水平與HIF-1α、HIF-2α表達(dá)水平及端粒長(zhǎng)度的相關(guān)性。結(jié)果顯示,隨著低氧時(shí)間的延長(zhǎng),胃黏膜組織細(xì)胞損傷逐漸加重,ROS生成量逐漸升高,端粒長(zhǎng)度逐漸增加,TERT和HIF-1α mRNA及蛋白表達(dá)水平的變化趨勢(shì)與端粒長(zhǎng)度的變化趨勢(shì)一致,而HIF-2α表達(dá)水平未見(jiàn)明顯變化,僅在低氧7 d時(shí)表達(dá)增加;TERT mRNA表達(dá)水平與端粒長(zhǎng)度之間、TERT mRNA和蛋白表達(dá)水平與HIF-1α之間均存在正相關(guān)性,而TERT mRNA表達(dá)水平與HIF-2α之間無(wú)明顯相關(guān)性。上述結(jié)果提示,急性高原嚴(yán)重低氧環(huán)境下,機(jī)體產(chǎn)生大量ROS,損傷胃黏膜組織細(xì)胞,同時(shí)又通過(guò)HIF-1α上調(diào)TERT的表達(dá)及端粒酶活性,增加細(xì)胞端粒長(zhǎng)度,使胃黏膜組織細(xì)胞產(chǎn)生適應(yīng)性反應(yīng),避免發(fā)生嚴(yán)重?fù)p傷。
[Abstract]:The aim of this study was to observe the effect of acute hypoxia on telomere length of gastric mucosa in rats and to explore its mechanism. The experimental group was randomly divided into three groups: control group (Lanzhou, 1 500 mNM) and experimental group (low pressure oxygen chamber, 5 000 m),). According to the time of hypoxia exposure, the experimental group was divided into 3 groups, 10 rats in each group. After hypoxic exposure, the gastric tissue of rats in each group was taken and observed by HE staining, and the telomere length of gastric mucosal cells was measured by real-time PCR method. The expression levels of telomerase reverse transcriptase (telomerase reverse transcriptase,TERT), hypoxia inducible factor 1 偽 (HIF-1 偽), HIF-2 偽 mRNA and protein were detected by real-time PCR and ELISA, respectively. The correlation between TERT expression and HIF-1 偽, HIF-2 偽 expression and telomere length was analyzed. The results showed that with the prolongation of hypoxic time, the injury of gastric mucosal tissue cells was gradually aggravated, the ROS production and telomere length were gradually increased, and the expression of TERT and HIF-1 偽 mRNA and protein were consistent with the changes of telomere length. However, there was no significant change in HIF-2 偽 expression level. Only at 7 days after hypoxia, there was a positive correlation between the expression level of, TERT mRNA and protein and the expression of, TERT mRNA and protein in telomere length, but there was no significant correlation between TERT mRNA expression level and HIF-2 偽 expression. These results suggest that in acute high altitude and severe hypoxia, a large amount of ROS, damages gastric mucosal cells, at the same time, HIF-1 偽 upregulated the expression of TERT and telomerase activity, and increased the telomere length of the cells. Make gastric mucosal tissue cells produce adaptive response to avoid serious damage.
【作者單位】： 青海省人民醫(yī)院消化內(nèi)科;
【基金】：supported by the Natural Science Youth Foundation of Qinghai Province,China(No.2015-ZJ-941Q)
【分類(lèi)號(hào)】：R57
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本文編號(hào)：2290641