Expression changes of Nrf2 and HO-1 in rat cortex following traumatic brain injury after hypoxic preconditioning

doi:10.3877/cma.j.issn.2095-9141.2015.04.009

Abstract

Abstract:

Objective

To investigatetheexpression changesof nuclear factor erythroid 2-related factor 2(Nrf2)and heme oxygenase-1(HO-1)in rat cortex following traumatic brain injury after hypoxic preconditioning.

Methods

Two hundred and sixteen adult male Sprague Dawley rats were randomly divided into control group(Con),hypoxic preconditioning group(HP),traumatic brain injury group(TBI)and hypoxic preconditioning+traumatic brain injury group(HP+TBI).Con and TBI groups had 12 rats respectively,TBI or HP+TBI group was subdivided into 8 groups according to sacrifice time points,namely group 1 h,3 h,6 h,12 h,24 h,3 d,7 d and 14d(n=12).TBImodels were made by the Feeney’s improved equipment and hypoxic preconditioning models were made by Hypobaric chamber for 3 days(-50kPa、3 h/d).The expression of Nrf2 and HO-1 in the brain cortex was detected by immunohistochemistry and western blotting.

Results

The expression of Nrf2 and HO-1 began to increase at 1 h,reached the peak at 24 h,and decreased slowly at 3 d after TBI.At the time points of 1 h to 7 d,the expression of Nrf2 and HO-1 in the HP+TBIor TBIgroup was significantly higher than those in the Con or HPgroup(p<0.05).After consecutive three days hypoxic preconditioning,the expression of Nrf2 and HO-1 had no significant difference between HPand Con groups,but the expression of Nrf2 and HO-1 in the HP+TBI group was higher than those in the TBI group from 1 h to 7 d(p<0.05).

Conclusion

Hypoxic preconditioning up-regulates the expression of Nrf2 and HO-1 in the brain cortex,which enhancestheanti-oxidativeability of brain after TBI.

Key words: Traumatic brain injury, Nuclear factor erythroid 2-related factor 2, Heme ox-ygenase-1, Hypoxic preconditioning

Longfei Shu, Jiachuan Liu, Jinbiao Wang, Yongming Zhang, Xing Zhang, Yanyan Yang, Tao Ma, Wenjiang Sun, Jianwei Zhuo. Expression changes of Nrf2 and HO-1 in rat cortex following traumatic brain injury after hypoxic preconditioning[J]. Chinese Journal of Neurotraumatic Surgery(Electronic Edition), 2015, 01(04): 227-231.

/ / Recommend

Add to citation manager EndNote|Ris|BibTeX

URL: https://zhsjcswkdzzz.cma-cmc.com.cn/EN/10.3877/cma.j.issn.2095-9141.2015.04.009

https://zhsjcswkdzzz.cma-cmc.com.cn/EN/Y2015/V01/I04/227

Figures/Tables 6

References 9

［1］	Hatic H,Kane MJ,Saykally JN,et al.Modulation of transcription factor Nrf2 in an in vitro model of traumatic brain injury［J］.JNeurotrauma,2012,29(6):1188-1196.
［2］	Yan W,Wang HD,Hu ZG,et al.Activation of Nrf2-ARE pathway in brain after traumatic brain injury［J］.Neurosci Lett,2008,431(2):150-154.
［3］	Obrenovitch TP.Molecular physiology of preconditioning induced brain tolerance to ischemia［J］.Physiol Rev,2008,88(1):211-247.
［4］	Huang XS,Chen HP,Yu HH,et al.Nrf2-dependent upregulation of antioxidative enzymes:a novel pathway for hypoxic preconditioning-mediated delayed cardioprotection［J］.Mol Cell Biochem,2013,Sep 19.［Epub ahead of print］.
［5］	疏龙飞,刘家传,王金标,等.缺氧预处理对颅脑损伤大鼠抗氧化应激和神经功能的影响［J］.中华神经医学杂志,2014,13(6):576-580.
［6］	Bryan HK,Olayanju A,Goldring CE,et al.The Nrf2 cell defence pathway:Keap1-dependent and-independent mechanisms of regulation［J］.Biochem Pharmacol,2013,85(6):705-717.
［7］	孟华星,郭军红,严澎.重组人促红细胞生成素对急性脑缺血大鼠Nrf2及HO-1表达的影响［J］.中华神经医学杂志,2012,11(2):134-137.
［8］	Wang Z,Ma C,Meng CJ,et al.Melatonin activates the Nrf2-ARE pathway when it protects against early brain injury in a subarachnoid hemorrhage model［J］.JPineal Res,2012,53(2):129-137.
［9］	Tanji K,Maruyama A,Odagiri S,et al.Keap1 is localized in neuronal and glial cytoplasmic inclusions in various neurodegenerative diseases［J］.J Neuropathol Exp Neurol,2013,72(1):18-28.

		对照组	伤后1 h	伤后3 h	伤后6 h	伤后12 h	伤后24 h	伤后3 d	伤后7 d	伤后14 d	F值	P值
例数		6	6	6	6	6	6	6	6	6
Nrf2光密度	未缺氧	0.134±0.024	0.170±0.031^a	0.187±0.034^a	0.227±0.018^a	0.266±0.036^a	0.330±0.035^a	0.224±0.028^a	0.152±0.025^a	0.136±0.018^a	31.640	0.000
Nrf2光密度	缺氧预处理	0.141±0.023	0.219±0.026^ab	0.265±0.030^ab	0.309±0.047^ab	0.356±0.029^aba	0.450±0.037^ab	0.303±0.056^ab	0.215±0.040^ab	0.165±0.032	41.672	0.000
HO-1光密度	未缺氧	0.144±0.025	0.177±0.026^a	0.207±0.032^a	0.252±0.045^a	0.304±0.041^a	0.371±0.037^a	0.260±0.031^a	0.186±0.034^a	0.147±0.029	30.132	0.000
HO-1光密度	缺氧预处理	0.149±0.029	0.216±0.031^ab	0.250±0.035^ab	0.325±0.049^ab	0.374±0.049^ab	0.447±0.045^ab	0.326±0.050^ab	0.234±0.035^ab	0.162±0.016	38.515	0.000

		对照组	伤后1 h	伤后3 h	伤后6 h	伤后12 h	伤后24 h	伤后3 d	伤后7 d	伤后14 d	F值	P值
例数		6	6	6	6	6	6	6	6	6
Nrf2光密度	未缺氧	0.134±0.024	0.170±0.031^a	0.187±0.034^a	0.227±0.018^a	0.266±0.036^a	0.330±0.035^a	0.224±0.028^a	0.152±0.025^a	0.136±0.018^a	31.640	0.000
Nrf2光密度	缺氧预处理	0.141±0.023	0.219±0.026^ab	0.265±0.030^ab	0.309±0.047^ab	0.356±0.029^aba	0.450±0.037^ab	0.303±0.056^ab	0.215±0.040^ab	0.165±0.032	41.672	0.000
HO-1光密度	未缺氧	0.144±0.025	0.177±0.026^a	0.207±0.032^a	0.252±0.045^a	0.304±0.041^a	0.371±0.037^a	0.260±0.031^a	0.186±0.034^a	0.147±0.029	30.132	0.000
HO-1光密度	缺氧预处理	0.149±0.029	0.216±0.031^ab	0.250±0.035^ab	0.325±0.049^ab	0.374±0.049^ab	0.447±0.045^ab	0.326±0.050^ab	0.234±0.035^ab	0.162±0.016	38.515	0.000

		对照组	伤后1 h	伤后3 h	伤后6 h	伤后12 h	伤后24 h	伤后3 d	伤后7 d	伤后14 d	F值	P值
例数		6	6	6	6	6	6	6	6	6
Nrf2/β-actin	未缺氧	0.223±0.028	0.309±0.019^a	0.387±0.029^a	0.520±0.029^a	0.667±0.047^a	0.771±0.069^a	0.466±0.031^a	0.334±0.034^a	0.219±0.014	82.204	0.000
Nrf2/β-actin	缺氧预处理	0.247±0.048	0.367±0.041^ab	0.512±0.039^ab	0.647±0.031^ab	0.834±0.051^ab	1.051±0.112^ab	0.603±0.053^ab	0.389±0.072^ab	0.224±0.032	110.888	0.000
HO-1/β-actin	未缺氧	0.239±0.036	0.320±0.030^a	0.406±0.028^a	0.532±0.039^a	0.657±0.049^a	0.806±0.042^a	0.516±0.046^a	0.363±0.040^a	0.244±0.036	73.221	0.000
HO-1/β-actin	缺氧预处理	0.261±0.029	0.422±0.040^ab	0.529±0.061^ab	0.648±0.050^ab	0.792±0.066^ab	1.016±0.093^ab	0.716±0.083^ab	0.487±0.063^ab	0.277±0.049	47.324	0.000

		对照组	伤后1 h	伤后3 h	伤后6 h	伤后12 h	伤后24 h	伤后3 d	伤后7 d	伤后14 d	F值	P值
例数		6	6	6	6	6	6	6	6	6
Nrf2/β-actin	未缺氧	0.223±0.028	0.309±0.019^a	0.387±0.029^a	0.520±0.029^a	0.667±0.047^a	0.771±0.069^a	0.466±0.031^a	0.334±0.034^a	0.219±0.014	82.204	0.000
Nrf2/β-actin	缺氧预处理	0.247±0.048	0.367±0.041^ab	0.512±0.039^ab	0.647±0.031^ab	0.834±0.051^ab	1.051±0.112^ab	0.603±0.053^ab	0.389±0.072^ab	0.224±0.032	110.888	0.000
HO-1/β-actin	未缺氧	0.239±0.036	0.320±0.030^a	0.406±0.028^a	0.532±0.039^a	0.657±0.049^a	0.806±0.042^a	0.516±0.046^a	0.363±0.040^a	0.244±0.036	73.221	0.000
HO-1/β-actin	缺氧预处理	0.261±0.029	0.422±0.040^ab	0.529±0.061^ab	0.648±0.050^ab	0.792±0.066^ab	1.016±0.093^ab	0.716±0.083^ab	0.487±0.063^ab	0.277±0.049	47.324	0.000

[1]	Ying Wang, Deping Wu, Yu Liu, Guodong Liu. MiR-9-5p reduces neuroinflammation and apoptosis in rats with traumatic brain injury by down-regulating CXCR4 [J]. Chinese Journal of Cell and Stem Cell(Electronic Edition), 2024, 14(02): 65-72.
[2]	Shousen Wang, Shilong Fu, Liang Xian, Long Lin. Further understanding of the prevention mechanism and effects for intraoperative encephalocele by controlled decompression technique in patients with traumatic brain injury [J]. Chinese Journal of Neurotraumatic Surgery(Electronic Edition), 2024, 10(05): 257-262.
[3]	Dongyang Wu, Xiangdan Lin, Zuolin Shi, Yulong Zhao, Zhen Wang, An'guo Wen, Xin Ji, Juzhi Li, Mingguang Zhao. Application value of NF-L，NLRP3，and S100B proteins in assessing the severity and prognosis of traumatic brain injury [J]. Chinese Journal of Neurotraumatic Surgery(Electronic Edition), 2024, 10(05): 279-285.
[4]	Dongsheng Pan, Guobiao Liang. Latest developments and future trends in the treatment of traumatic brain injury [J]. Chinese Journal of Neurotraumatic Surgery(Electronic Edition), 2024, 10(04): 193-197.
[5]	Liangfu Zhou. Diagnosis and treatment of blast-related traumatic brain injury [J]. Chinese Journal of Neurotraumatic Surgery(Electronic Edition), 2024, 10(03): 129-131.
[6]	Shenghao Zhang, Jie Zhou, Pengfei Yao, Changdong Li, Xiaodong Qu, Yaqiang Nan, Li Cao. Role and mechanism of celastrol in secondary injury after traumatic brain injury [J]. Chinese Journal of Neurotraumatic Surgery(Electronic Edition), 2024, 10(03): 132-140.
[7]	Changchun Cong, Chunlin Wang, Xiaogang Wu, Jinbiao Wang, Fubin Zhang, Lei Sun, Li Wang. Risk factors and etiology of ventilator-associated pneumonia in patients with severe traumatic brain injury [J]. Chinese Journal of Neurotraumatic Surgery(Electronic Edition), 2024, 10(03): 151-157.
[8]	Jinpeng Mao, Zhihe Tao, Qi Liu, Yong Wang, Ming Zhou, Jinsong Chen, Shaobin Tian. Experience of successful conservative management of traumatic large epidural hematoma: a report of 10 cases [J]. Chinese Journal of Neurotraumatic Surgery(Electronic Edition), 2024, 10(03): 164-168.
[9]	Qiang Xin, Wenhao Zhu, Chuan He, Wenchen Li, Bo Chen, Haifeng Wang. Effect of glial cell-derived exosomal miRNAs on neuroinflammation after traumatic brain injury [J]. Chinese Journal of Neurotraumatic Surgery(Electronic Edition), 2024, 10(03): 169-173.
[10]	Ruhai Wang, Shen Wang, Min Zhang, Chun Li, Chao Han, Qiang Yu, Haicheng Hu, Xizhen Li. Analysis of influencing factors of short-term mortality risk in patients with severe traumatic brain injury after decompressive craniectomy [J]. Chinese Journal of Brain Diseases and Rehabilitation(Electronic Edition), 2024, 14(05): 285-291.
[11]	Nan Si, Hongtao Sun. Research progress on risk factors of renal dysfunction after traumatic brain injury [J]. Chinese Journal of Brain Diseases and Rehabilitation(Electronic Edition), 2024, 14(05): 300-305.
[12]	Zhiheng Hu, Hongbo Ren, Zhiyuan Song, Yungang Zhao, Xiaozheng Han. Relationship between serum sTIM-3 and its ligand Gal-9, CEACAM-1 and the degree of brain injury and prognosis in patients with traumatic brain injury [J]. Chinese Journal of Brain Diseases and Rehabilitation(Electronic Edition), 2024, 14(04): 201-207.
[13]	Shen Wang, Ruhai Wang, Chun Li, Zhen Yang, Feilin Sun. Risk factors analysis and prediction model construction of prolonged length of stay in patients with moderate and severe traumatic brain injury [J]. Chinese Journal of Brain Diseases and Rehabilitation(Electronic Edition), 2024, 14(03): 146-153.
[14]	Fangkun Jing, Yanfeng Li. Current status and prospect of surgical treatment of chronic disturbance of consciousness after traumatic brain injury [J]. Chinese Journal of Brain Diseases and Rehabilitation(Electronic Edition), 2024, 14(03): 129-132.
[15]	Yan Wang, Haiqian Liang, Shanshan Guo. Research advances in role of inflammasome in traumatic brain injury [J]. Chinese Journal of Brain Diseases and Rehabilitation(Electronic Edition), 2024, 14(03): 177-181.

Please choose a citation manager

Content to export