Effects of edaravone on apoptosis and expression of apoptotic proteins in hippocampal neurons of intermittent hypoxia rats_Chinese Journal of Respiratory and Critical Care Medicine

Authors：

 WANG Ling ¹ , WANG Yuan ¹ , ZHANG Jiabin ¹ , WANG Yanhui ² , ZHANG Min ³

1. Department of Respiratory Medicine, North China University of Science and Technology Affiliated Hospital, Tangshan, Hebei 063000, P. R. China;
2. Clinical Medical College, North China University of Science and Technology, Tangshan, Hebei 063000, P. R. China;
3. Department of Respiratory Medicine, First Hospital of Qinhuangdao, Qinhuangdao, Hebei 066000, P. R. China;

Corresponding?author：

WANG Ling, Email: 906874749@qq.com

Keywords：

Obstructive sleep apnea-hypopnea syndrome; Hypoxia; Edaravone; Apoptosis

DOI：

10.7507/1671-6205.202006030

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Objective To explore effects of edaravone on apoptosis and expressions of apoptotic proteins Smac and XIAP in hippocampal CA1 pyramidal cell of rats under intermittent hypoxia. Methods A total of 96 adult male Wistar rats were randomly divided into control group, 5% intermittent hypoxic group and edaravone group, and each group was divided into 4 time groups at 7 d, 14 d, 21 d and 28 d, respectively, with 8 rats in each subgroup. The content of reactive oxygen species (ROS) in hippocampal tissues of the experimental rats was detected by the reactive oxygen species detection kit. Immunohistochemistry and Western blot were used to detect the expressions of Smac and XIAP protein in hippocampal CA1 region. The Tunel method detected the apoptosis of neurons. Results Compared with the control group, the content of ROS, the expressions of Smac and XIAP proteins and the neuronal apoptosis index in the hippocampus were increased in the 5% intermittent hypoxia group and the edaravone group at each time point (all P<0.05). The content of ROS, the Smac protein expression and the neuronal apoptosis index in the edaravone group were significantly lower than those in the 5% intermittent hypoxia group (all P<0.05). The expression of XIAP protein in the edaravone group was significantly higher than that in the 5% intermittent hypoxia group (P<0.05). Conclusion Edaravone may improve the antioxidant capacity of the body by scavenging oxygen free radicals and regulate Smac and XIAP- mediated apoptosis, thus playing a protective role on neurons.

Citation： WANG Ling, WANG Yuan, ZHANG Jiabin, WANG Yanhui, ZHANG Min. Effects of edaravone on apoptosis and expression of apoptotic proteins in hippocampal neurons of intermittent hypoxia rats. Chinese Journal of Respiratory and Critical Care Medicine, 2021, 20(9): 632-636. doi: 10.7507/1671-6205.202006030 Copy

1.	Zhu X, Wang P, Liu H, et al. Changes and significance of SYP and GAP-43 expression in the hippocampus of CIH rats. Int J Med Sci, 2019, 16(3): 394-402.
2.	Koehler U, Cassel W, Hildebrandt O, et al. Obstructive sleep apnea in neurological diseases: specially as a risk factor for stroke. Nervenarzt, 2014, 85(1): 35-42.
3.	Olea E, Agapito MT, Gallego-Martin T, et al. Intermittent hypoxia and diet-induced obesity: effects on oxidative status, sympathetic tone, plasma glucose and insulin levels, and arterial pressure. J Appl Physiol (1985), 2014, 117(7): 706-719.
4.	王玲, 張盼盼, 韓曉慶, 等. 細胞外信號調節激酶抑制劑對間歇低氧早期大鼠神經元凋亡及 P53 表達的影響. 中華老年心腦血管病雜志, 2019, 21(7): 754-758.
5.	Wang SD, Fu YY, Han XY, et al. Hyperbaric oxygen preconditioning protects against cerebral ischemia/reperfusion injury by inhibiting mitochondrial apoptosis and energy metabolism disturbance. Neurochem Res, 2021, 46(4): 866-877.
6.	王玲, 王袁, 張嘉賓, 等. 細胞外信號調節激酶抑制劑對間歇低氧大鼠認知功能的影響. 中華老年心腦血管病雜志, 2020, 22(8): 866-870.
7.	Moreno-Indias I, Torres M, Montserrat JM, et al. Intermittent hypoxia alters gut microbiota diversity in a mouse model of sleep apnoea. Eur Respir J, 2015, 45(4): 1055-1065.
8.	李麗芳, 原新慧, 凌繼祖, 等. 間歇低氧導致大鼠腎臟損傷以及依達拉奉的干預作用. 中國呼吸與危重監護雜志, 2019, 18(4): 331-338.
9.	王玲, 張盼盼, 付愛雙, 等. 間歇低氧對大鼠認知功能的影響及其分子機制的研究. 中華解剖與臨床雜志, 2020, 25(3): 322-330.
10.	Martinez M, Rossetto IMU, Neto FSL, et al. Interactions of ethanol and caffeine on apoptosis in the rat cerebellum (voluntary ethanol consumers). Cell Biol Int, 2018, 42(11): 1575-1583.
11.	Jeong S, Jo MJ, Yun HK, et al. Cannabidiol promotes apoptosis via regulation of XIAP/Smac in gastric cancer. Cell Death Dis, 2019, 10(11): 846.
12.	Liu X, Hong L, Peng W, et al. The neuroprotective effect of miR-181a after oxygen-glucose deprivation/reperfusion and the associated mechanism. J Mol Neurosci, 2019, 68(2): 261-274.
13.	王亮, 董偉. 高血糖對創傷性腦損傷后皮質 SMAC 和 XIAP 表達的影響. 檢驗醫學與臨床, 2019, 16(9): 1228-1231.
14.	Tian A, Ma H, Zhang R, et al. Edaravone improves spatial memory and modulates endoplasmic reticulum stress-mediated apoptosis after abdominal surgery in mice. Exp Ther Med, 2017, 14(1): 355-360.
15.	Li C, Mo Z, Lei J, et al. Edaravone attenuates neuronal apoptosis in hypoxic-ischemic brain damage rat model via suppression of TRAIL signaling pathway. Int J Biochem Cell Biol, 2018, 99: 169-177.
16.	齊登斌, 郭振元, 閆波, 等. 依達拉奉對癲癇持續狀態大鼠神經元凋亡及 XIAP、Caspase-3 表達的影響. 中外醫療, 2019, 38(3): 23-25.
17.	王玲, 張盼盼, 付愛雙, 等. 間歇低氧對大鼠海馬神經細胞突觸相關蛋白表達及認知功能的影響. 中華老年心腦血管病雜志, 2020, 22(5): 534-537.

1. Zhu X, Wang P, Liu H, et al. Changes and significance of SYP and GAP-43 expression in the hippocampus of CIH rats. Int J Med Sci, 2019, 16(3): 394-402.
2. Koehler U, Cassel W, Hildebrandt O, et al. Obstructive sleep apnea in neurological diseases: specially as a risk factor for stroke. Nervenarzt, 2014, 85(1): 35-42.
3. Olea E, Agapito MT, Gallego-Martin T, et al. Intermittent hypoxia and diet-induced obesity: effects on oxidative status, sympathetic tone, plasma glucose and insulin levels, and arterial pressure. J Appl Physiol (1985), 2014, 117(7): 706-719.
4. 王玲, 張盼盼, 韓曉慶, 等. 細胞外信號調節激酶抑制劑對間歇低氧早期大鼠神經元凋亡及 P53 表達的影響. 中華老年心腦血管病雜志, 2019, 21(7): 754-758.
5. Wang SD, Fu YY, Han XY, et al. Hyperbaric oxygen preconditioning protects against cerebral ischemia/reperfusion injury by inhibiting mitochondrial apoptosis and energy metabolism disturbance. Neurochem Res, 2021, 46(4): 866-877.
6. 王玲, 王袁, 張嘉賓, 等. 細胞外信號調節激酶抑制劑對間歇低氧大鼠認知功能的影響. 中華老年心腦血管病雜志, 2020, 22(8): 866-870.
7. Moreno-Indias I, Torres M, Montserrat JM, et al. Intermittent hypoxia alters gut microbiota diversity in a mouse model of sleep apnoea. Eur Respir J, 2015, 45(4): 1055-1065.
8. 李麗芳, 原新慧, 凌繼祖, 等. 間歇低氧導致大鼠腎臟損傷以及依達拉奉的干預作用. 中國呼吸與危重監護雜志, 2019, 18(4): 331-338.
9. 王玲, 張盼盼, 付愛雙, 等. 間歇低氧對大鼠認知功能的影響及其分子機制的研究. 中華解剖與臨床雜志, 2020, 25(3): 322-330.
10. Martinez M, Rossetto IMU, Neto FSL, et al. Interactions of ethanol and caffeine on apoptosis in the rat cerebellum (voluntary ethanol consumers). Cell Biol Int, 2018, 42(11): 1575-1583.
11. Jeong S, Jo MJ, Yun HK, et al. Cannabidiol promotes apoptosis via regulation of XIAP/Smac in gastric cancer. Cell Death Dis, 2019, 10(11): 846.
12. Liu X, Hong L, Peng W, et al. The neuroprotective effect of miR-181a after oxygen-glucose deprivation/reperfusion and the associated mechanism. J Mol Neurosci, 2019, 68(2): 261-274.
13. 王亮, 董偉. 高血糖對創傷性腦損傷后皮質 SMAC 和 XIAP 表達的影響. 檢驗醫學與臨床, 2019, 16(9): 1228-1231.
14. Tian A, Ma H, Zhang R, et al. Edaravone improves spatial memory and modulates endoplasmic reticulum stress-mediated apoptosis after abdominal surgery in mice. Exp Ther Med, 2017, 14(1): 355-360.
15. Li C, Mo Z, Lei J, et al. Edaravone attenuates neuronal apoptosis in hypoxic-ischemic brain damage rat model via suppression of TRAIL signaling pathway. Int J Biochem Cell Biol, 2018, 99: 169-177.
16. 齊登斌, 郭振元, 閆波, 等. 依達拉奉對癲癇持續狀態大鼠神經元凋亡及 XIAP、Caspase-3 表達的影響. 中外醫療, 2019, 38(3): 23-25.
17. 王玲, 張盼盼, 付愛雙, 等. 間歇低氧對大鼠海馬神經細胞突觸相關蛋白表達及認知功能的影響. 中華老年心腦血管病雜志, 2020, 22(5): 534-537.

Chinese Journal of Respiratory and Critical Care Medicine

Effects of edaravone on apoptosis and expression of apoptotic proteins in hippocampal neurons of intermittent hypoxia rats

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