Expression of C/EBP homologous protein in lung tissue of chronic intermittent hypoxic rats and the effect of edaravone_Chinese Journal of Respiratory and Critical Care Medicine

Authors：

ZHANG Jiabin , GE Yanlei , LIU Conghui , ZHANG Panpan ,  WANG Hongyang , ZHU Xiaoying , LI Hongli , LI Zhenzhen

Affiliated Hospital of North China University of Technology, Tangshan, Hebei 063000, P. R. China;

Corresponding author：

WANG Hongyang, Email: tsmywhy@163.com

Keywords：

Chronic intermittent hypoxia; Obstructive sleep apnea hypopnea syndrome; Lung injury; C/EBP homologous protein; Edaravone

DOI：

10.7507/1671-6205.201809023

Video：

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Objective To investigate the expression of C/EBP homologous protein (CHOP) in lung tissue of chronic intermittent hypoxia rats, and explore the intervention effect of edaravone and its possible mechanism.Methods A total of 120 adult male Wistar rats were randomly divided into three groups: a normal control group (UC group), a chronic intermittent hypoxia group (CIH group), an edaravone intervention group (NE group), and a normal saline group (NS group). The above four groups were also randomly divided into five time subgroups of 3 days, 7 days, 14 days, 21 days and 28 days, respectively, with 6 rats in each time subgroup. The histopathological changes of lung tissue were observed by hematoxylin-eosin (HE) staining and the expression of CHOP in lung tissue was detected by immunohistochemical method.Results HE staining results showed that there was no obvious pathological change in UC group. The epithelial cells of lung tissue in CIH group showed edema, hyperemia, widening of alveolar septum and inflammatory cell infiltration. The pathological injury was more serious with the prolongation of intermittent hypoxia time. There were also pathological changes in NE group, but the degree of lung tissue injury was significantly lower than that in CIH group. The results of immunohistochemistry showed that the expression of CHOP in CIH group was significantly higher than that in UC group. The expression of CHOP in NE group was higher than that in UC group, but it was still significantly lower than that in CIH group.Conclusions The expression of CHOP protein in lung tissue of chronic intermittent hypoxic rats is enhanced and the high expression of CHOP protein plays a certain role in the lung injury of chronic intermittent hypoxia rats complicated with lung injury. Edaravone may protect lung tissue from chronic intermittent hypoxia by inhibiting the expression of CHOP.

Citation： ZHANG Jiabin, GE Yanlei, LIU Conghui, ZHANG Panpan, WANG Hongyang, ZHU Xiaoying, LI Hongli, LI Zhenzhen. Expression of C/EBP homologous protein in lung tissue of chronic intermittent hypoxic rats and the effect of edaravone. Chinese Journal of Respiratory and Critical Care Medicine, 2019, 18(4): 327-330. doi: 10.7507/1671-6205.201809023 Copy

1.	张嘉宾, 张盼盼, 王红阳, 等. 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. 中国现代医学杂志, 2016, 26(15): 38-43.
2.	Dewan NA, Nieto FJ, Somers VK. Intermittent hypoxemia and OSA: implications for comorbidities. Chest, 2015, 147(1): 266-274.
3.	刘志娟, 郝青林. 氧化应激在 OSAHS 合并代谢综合征作用机制研究进展. 临床肺科杂志, 2011, 16(9): 1435-1437.
4.	王玲, 张盼盼, 王红阳, 等. 线粒体自噬对间歇低氧早期大鼠认知功能影响的初探. 中华结核和呼吸杂志, 2014, 37(11): 840-844.
5.	Julian GS, Oliveira RW, Favaro VM, et al. Chronic intermittent hypoxia increases encoding pigment epithelium-derived factor gene expression, although not that of the protein itself, in the temporal cortex of rats. J Bras Pneumol, 2015, 41(1): 39-47.
6.	王金凤, 谢宇平, 马薇, 等. 阻塞性睡眠呼吸暂停低通气综合征与支气管哮喘关系的研究进展. 临床耳鼻咽喉头颈外科杂志, 2015, 29(4): 381-384.
7.	Oyadomari S, Mori M. Roles of CHOP/GADD153 in endoplasmic reticulum stress. Cell Death Differ, 2004, 11(4): 381-389.
8.	Rao J, Zhang C, Wang P, et al. C/EBP homologous protein (CHOP) contributes to hepatocyte death via the promotion of ERO1α signaling in acute liver failure. Biochem J, 2015, 466(2): 369-378.
9.	刘宝琴, 王华芹. 内质网应激与未折叠蛋白反应的研究进展. 中华肿瘤防治杂志, 2010, 17(11): 869-872.
10.	杜锡潮, 韩冰, 谢汝佳, 等. 肝纤维化大鼠肝脏中内质网应激相关分子 CHOP 和 TRB3 的表达变化. 中国病理生理杂志, 2013, 29(5): 906-912.
11.	张嘉宾, 张盼盼, 寇育乐, 等. 慢性间歇低氧大鼠肺泡上皮细胞 CCAAT/增强子结合蛋白同源蛋白(CHOP)表达增强. 细胞与分子免疫学杂志, 2016, 32(1): 79-83.
12.	Oldham RA, Berinstein EM, Medin JA. Lentiviral vectors in cancer immunotherapy. Immunotherapy, 2015, 7(3): 271-284.
13.	Morgan RA, Kakarla S. Genetic modification of T cells. Cancer J, 2014, 20(2): 145-150.
14.	Geng X, Doitsh G, Yang Z, et al. Efficient delivery of lentiviral vectors into resting human CD4 T cells. Gene Ther, 2014, 21(4): 444-449.
15.	王琪, 段冷昕. 内质网应激中 GRP78 和 ATF4-CHOP-Puma 信号通路与帕金森病的关系及其治疗靶点的研究进展. 神经药理学报, 2013, 3(3): 19-26.
16.	Ron D, Habener JF. CHOP, a novel developmentally regulated nuclear protein that dimerizes with transcription factors C/EBP and LAP and functions as a dominant-negative inhibitor of gene transcription. Genes Dev, 2002, 6(3): 439-453.
17.	曲鹏, 张鸿, 张正洪, 等. NGF 和 CGRP 对局灶性脑缺血再灌注后大鼠皮质 CHOP 蛋白表达的影响. 解剖科学进展, 2006, 12(3): 215-218.
18.	Tajima S, Soda M, Bando M, et al. Preventive effects of edaravone, a free radical scavenger, on lipopolysaccharide-induced lung injury in mice. Respirology, 2008, 13(5): 646-653.
19.	Zhi QM, Sun HC, Qian XM, et al. Edaravone, a novel antidote against lung injury and pulmonary fibrosis induced by paraquat?. Int Immunopharamacol, 2011, 11(1): 96-102.
20.	寇育乐, 张盼盼, 王红阳, 等. ACE2 在慢性间歇低氧肺组织氧化应激损伤中的作用. 四川大学学报(医学版), 2016, 47(1): 43-48.

1. 张嘉宾, 张盼盼, 王红阳, 等. 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. 中国现代医学杂志, 2016, 26(15): 38-43.
2. Dewan NA, Nieto FJ, Somers VK. Intermittent hypoxemia and OSA: implications for comorbidities. Chest, 2015, 147(1): 266-274.
3. 刘志娟, 郝青林. 氧化应激在 OSAHS 合并代谢综合征作用机制研究进展. 临床肺科杂志, 2011, 16(9): 1435-1437.
4. 王玲, 张盼盼, 王红阳, 等. 线粒体自噬对间歇低氧早期大鼠认知功能影响的初探. 中华结核和呼吸杂志, 2014, 37(11): 840-844.
5. Julian GS, Oliveira RW, Favaro VM, et al. Chronic intermittent hypoxia increases encoding pigment epithelium-derived factor gene expression, although not that of the protein itself, in the temporal cortex of rats. J Bras Pneumol, 2015, 41(1): 39-47.
6. 王金凤, 谢宇平, 马薇, 等. 阻塞性睡眠呼吸暂停低通气综合征与支气管哮喘关系的研究进展. 临床耳鼻咽喉头颈外科杂志, 2015, 29(4): 381-384.
7. Oyadomari S, Mori M. Roles of CHOP/GADD153 in endoplasmic reticulum stress. Cell Death Differ, 2004, 11(4): 381-389.
8. Rao J, Zhang C, Wang P, et al. C/EBP homologous protein (CHOP) contributes to hepatocyte death via the promotion of ERO1α signaling in acute liver failure. Biochem J, 2015, 466(2): 369-378.
9. 刘宝琴, 王华芹. 内质网应激与未折叠蛋白反应的研究进展. 中华肿瘤防治杂志, 2010, 17(11): 869-872.
10. 杜锡潮, 韩冰, 谢汝佳, 等. 肝纤维化大鼠肝脏中内质网应激相关分子 CHOP 和 TRB3 的表达变化. 中国病理生理杂志, 2013, 29(5): 906-912.
11. 张嘉宾, 张盼盼, 寇育乐, 等. 慢性间歇低氧大鼠肺泡上皮细胞 CCAAT/增强子结合蛋白同源蛋白(CHOP)表达增强. 细胞与分子免疫学杂志, 2016, 32(1): 79-83.
12. Oldham RA, Berinstein EM, Medin JA. Lentiviral vectors in cancer immunotherapy. Immunotherapy, 2015, 7(3): 271-284.
13. Morgan RA, Kakarla S. Genetic modification of T cells. Cancer J, 2014, 20(2): 145-150.
14. Geng X, Doitsh G, Yang Z, et al. Efficient delivery of lentiviral vectors into resting human CD4 T cells. Gene Ther, 2014, 21(4): 444-449.
15. 王琪, 段冷昕. 内质网应激中 GRP78 和 ATF4-CHOP-Puma 信号通路与帕金森病的关系及其治疗靶点的研究进展. 神经药理学报, 2013, 3(3): 19-26.
16. Ron D, Habener JF. CHOP, a novel developmentally regulated nuclear protein that dimerizes with transcription factors C/EBP and LAP and functions as a dominant-negative inhibitor of gene transcription. Genes Dev, 2002, 6(3): 439-453.
17. 曲鹏, 张鸿, 张正洪, 等. NGF 和 CGRP 对局灶性脑缺血再灌注后大鼠皮质 CHOP 蛋白表达的影响. 解剖科学进展, 2006, 12(3): 215-218.
18. Tajima S, Soda M, Bando M, et al. Preventive effects of edaravone, a free radical scavenger, on lipopolysaccharide-induced lung injury in mice. Respirology, 2008, 13(5): 646-653.
19. Zhi QM, Sun HC, Qian XM, et al. Edaravone, a novel antidote against lung injury and pulmonary fibrosis induced by paraquat?. Int Immunopharamacol, 2011, 11(1): 96-102.
20. 寇育乐, 张盼盼, 王红阳, 等. ACE2 在慢性间歇低氧肺组织氧化应激损伤中的作用. 四川大学学报(医学版), 2016, 47(1): 43-48.

Chinese Journal of Respiratory and Critical Care Medicine

Expression of C/EBP homologous protein in lung tissue of chronic intermittent hypoxic rats and the effect of edaravone

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