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：

Export PDF Favorites Scan Get Citation

Abstract Full text Figures/Tables Video References Cited by

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.	張嘉賓, 張盼盼, 王紅陽, 等. 磷酸化蛋白激酶樣內質網激酶、C/EBP 同源蛋白在慢性間歇低氧大鼠肺組織中的表達變化及意義. 中國現代醫學雜志, 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.	劉志娟, 郝青林. 氧化應激在 OSAHS 合并代謝綜合征作用機制研究進展. 臨床肺科雜志, 2011, 16(9): 1435-1437.
4.	王玲, 張盼盼, 王紅陽, 等. 線粒體自噬對間歇低氧早期大鼠認知功能影響的初探. 中華結核和呼吸雜志, 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.	王金鳳, 謝宇平, 馬薇, 等. 阻塞性睡眠呼吸暫停低通氣綜合征與支氣管哮喘關系的研究進展. 臨床耳鼻咽喉頭頸外科雜志, 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.	劉寶琴, 王華芹. 內質網應激與未折疊蛋白反應的研究進展. 中華腫瘤防治雜志, 2010, 17(11): 869-872.
10.	杜錫潮, 韓冰, 謝汝佳, 等. 肝纖維化大鼠肝臟中內質網應激相關分子 CHOP 和 TRB3 的表達變化. 中國病理生理雜志, 2013, 29(5): 906-912.
11.	張嘉賓, 張盼盼, 寇育樂, 等. 慢性間歇低氧大鼠肺泡上皮細胞 CCAAT/增強子結合蛋白同源蛋白(CHOP)表達增強. 細胞與分子免疫學雜志, 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. 內質網應激中 GRP78 和 ATF4-CHOP-Puma 信號通路與帕金森病的關系及其治療靶點的研究進展. 神經藥理學報, 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.	曲鵬, 張鴻, 張正洪, 等. NGF 和 CGRP 對局灶性腦缺血再灌注后大鼠皮質 CHOP 蛋白表達的影響. 解剖科學進展, 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.	寇育樂, 張盼盼, 王紅陽, 等. ACE2 在慢性間歇低氧肺組織氧化應激損傷中的作用. 四川大學學報(醫學版), 2016, 47(1): 43-48.

1. 張嘉賓, 張盼盼, 王紅陽, 等. 磷酸化蛋白激酶樣內質網激酶、C/EBP 同源蛋白在慢性間歇低氧大鼠肺組織中的表達變化及意義. 中國現代醫學雜志, 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. 劉志娟, 郝青林. 氧化應激在 OSAHS 合并代謝綜合征作用機制研究進展. 臨床肺科雜志, 2011, 16(9): 1435-1437.
4. 王玲, 張盼盼, 王紅陽, 等. 線粒體自噬對間歇低氧早期大鼠認知功能影響的初探. 中華結核和呼吸雜志, 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. 王金鳳, 謝宇平, 馬薇, 等. 阻塞性睡眠呼吸暫停低通氣綜合征與支氣管哮喘關系的研究進展. 臨床耳鼻咽喉頭頸外科雜志, 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. 劉寶琴, 王華芹. 內質網應激與未折疊蛋白反應的研究進展. 中華腫瘤防治雜志, 2010, 17(11): 869-872.
10. 杜錫潮, 韓冰, 謝汝佳, 等. 肝纖維化大鼠肝臟中內質網應激相關分子 CHOP 和 TRB3 的表達變化. 中國病理生理雜志, 2013, 29(5): 906-912.
11. 張嘉賓, 張盼盼, 寇育樂, 等. 慢性間歇低氧大鼠肺泡上皮細胞 CCAAT/增強子結合蛋白同源蛋白(CHOP)表達增強. 細胞與分子免疫學雜志, 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. 內質網應激中 GRP78 和 ATF4-CHOP-Puma 信號通路與帕金森病的關系及其治療靶點的研究進展. 神經藥理學報, 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. 曲鵬, 張鴻, 張正洪, 等. NGF 和 CGRP 對局灶性腦缺血再灌注后大鼠皮質 CHOP 蛋白表達的影響. 解剖科學進展, 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. 寇育樂, 張盼盼, 王紅陽, 等. ACE2 在慢性間歇低氧肺組織氧化應激損傷中的作用. 四川大學學報(醫學版), 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

Abstract Full text Figures/Tables Video References Cited by

Previous Article

Next Article

Format

Content