磷酸化蛋白激酶样内质网激酶、C/EBP同源蛋白在慢性间歇低氧大鼠肺组织中的表达变化及意义

Expression and significance of p-PERK and CHOP protein in lung tissue of rats in chronic intermittent hypoxia

摘要:

目的  探讨慢性间歇低氧（CIH）大鼠肺组织中磷酸化的蛋白激酶样内质网激酶（p-PERK）、CCAAT增强子结合蛋白（C/EBP）同源蛋白（CHOP）表达变化及意义。方法  将60只大鼠随机分成正常组（UC组）、CIH组，每组各自分成3、7、14、21和28 d 5个时间亚组。采用HE法观察UC组和CIH组大鼠肺组织病理形态变化；采用免疫组织化学法检测p-PERK、CHOP蛋白表达及两者的相关性；采用逆转录-聚合酶链反应（RT-PCR）方法检测两组大鼠肺组织CHOP mRNA表达。结果  ①CIH组肺泡壁及间质轻度水肿，少量炎症细胞浸润，肺泡结构紊乱，部分肺泡融合；UC组大鼠肺组织无明显病理变化。②CIH组肺组织p-PERK、CHOP蛋白表达高于UC组，于21 d表达最高。③CIH组肺组织CHOP mRNA表达高于UC组，于21 d表达最高。④P-PERK、CHOP表达的上调呈正相关。结论  慢性间歇低氧可引起肺组织损伤，而p-PERK、CHOP蛋白的活化表达在慢性间歇低氧大鼠肺组织的损伤中可能存在一定的作用。

Abstract:

Objective To investigate the changes of RNA-dependent protein kinase-like endoplasmic reticulum kinase (p-PERK) and CCAAT enhancer binding protein (C/EBP) homology protein (CHOP) expression in lung tissue of rats with chronic intermittent hypoxia (CIH). Methods Wistar rats were selected to produce a sleep rat model with chronic intermittent hypoxia. Sixty rats were randomly divided into normal group (UC) and CIH group; and each group was separated into 3-d, 7-d, 14-d and 21-d and 28-d five subgroups. HE method was used to observe the pathological changes of the rat lung tissue in the control and model groups. Immunohistochemical method was used to detect the p-PERK and CHOP expressions and their correlation was analyzed. RT-PCR was adopted for detection of CHOP mRNA expression in the rat lung tissue of the two groups. Results In the CIH group, there were mild edema and a small amount of inflammatory cell infiltration in the alveolar walls and interstitium, alveolar structure disorder, and partial alveolar fusion; while there were no obvious pathological changes of rat lung tissue in the UC group. The expressions of p-PERK and CHOP in the CIH group was higher than those in the UC group, the expression levels on the 21st d were the highest. The expression of CHOP mRNA in the lung tissue of the CIH group was higher than that in the lung tissue of the UC group, which was the highest on the 21st d. The up-regulated p-PERK and CHOP expressions were in a positive correlation. Conclusions Chronic intermittent hypoxia can cause lung injury; and the up-regulated expressions of p-PERK and CHOP may play certain roles in the injury of lung tissue in rats with chronic intermittent hypoxia.