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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Abstract Full text Figures/Tables Video References Cited by

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, 张盼盼, 韩晓庆, 等. 细胞外信号调节激酶抑制剂对间歇低氧早期大鼠神经元凋亡及 P53 表达的影响. 中华老年心脑血管病杂志, 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, 张嘉宾, 等. 细胞外信号调节激酶抑制剂对间歇低氧大鼠认知功能的影响. 中华老年心脑血管病杂志, 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.	李丽芳, 原新慧, 凌继祖, 等. 间歇低氧导致大鼠肾脏损伤以及依达拉奉的干预作用. 中国呼吸与危重监护杂志, 2019, 18(4): 331-338.
9.	王玲, 张盼盼, 付爱双, 等. 间歇低氧对大鼠认知功能的影响及其分子机制的研究. 中华解剖与临床杂志, 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, 董伟. 高血糖对创伤性脑损伤后皮质 SMAC 和 XIAP 表达的影响. 检验医学与临床, 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.	齐登斌, 郭振元, 闫波, 等. 依达拉奉对癫痫持续状态大鼠神经元凋亡及 XIAP、Caspase-3 表达的影响. 中外医疗, 2019, 38(3): 23-25.
17.	王玲, 张盼盼, 付爱双, 等. 间歇低氧对大鼠海马神经细胞突触相关蛋白表达及认知功能的影响. 中华老年心脑血管病杂志, 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, 张盼盼, 韩晓庆, 等. 细胞外信号调节激酶抑制剂对间歇低氧早期大鼠神经元凋亡及 P53 表达的影响. 中华老年心脑血管病杂志, 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, 张嘉宾, 等. 细胞外信号调节激酶抑制剂对间歇低氧大鼠认知功能的影响. 中华老年心脑血管病杂志, 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. 李丽芳, 原新慧, 凌继祖, 等. 间歇低氧导致大鼠肾脏损伤以及依达拉奉的干预作用. 中国呼吸与危重监护杂志, 2019, 18(4): 331-338.
9. 王玲, 张盼盼, 付爱双, 等. 间歇低氧对大鼠认知功能的影响及其分子机制的研究. 中华解剖与临床杂志, 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, 董伟. 高血糖对创伤性脑损伤后皮质 SMAC 和 XIAP 表达的影响. 检验医学与临床, 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. 齐登斌, 郭振元, 闫波, 等. 依达拉奉对癫痫持续状态大鼠神经元凋亡及 XIAP、Caspase-3 表达的影响. 中外医疗, 2019, 38(3): 23-25.
17. 王玲, 张盼盼, 付爱双, 等. 间歇低氧对大鼠海马神经细胞突触相关蛋白表达及认知功能的影响. 中华老年心脑血管病杂志, 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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