Effects of Exendin-4 on cognitive function and Nrf2 signaling pathway in rats with traumatic brain injury
10.3760/cma.j.issn.1674-6554.2019.01.006
- VernacularTitle:Exendin-4对颅脑创伤大鼠认知功能及Nrf2信号通路的影响
- Author:
Qicai ZHANG
1
,
2
;
Sai ZHANG
;
Yongge WANG
;
Ran ZHAO
Author Information
1. 天津医科大学研究生院 300070
2. 天津市神经创伤修复重点实验室
- Keywords:
Traumatic brain injury;
Exendin-4;
Alzheimer's disease;
Nuclear factor erythroid 2-related factor 2;
Aβ1-42
- From:
Chinese Journal of Behavioral Medicine and Brain Science
2019;28(1):33-37
- CountryChina
- Language:Chinese
-
Abstract:
Objective To explore the effect of Exendin-4 on dementia after traumatic brain injury (TBI) in rats and its related mechanism.Methods Thirty SD rats were randomly divided into sham group (n=10),TBI group(n=10) and Exendin-4 group(n=10).Cortical impact injury was used to construct the TBI model.Morris water maze test was used to test the memory function of rats one month after TBI.The beta-amyloid protein (Aβ1-42) and nuclear factor erythroid-2-related factor 2 (Nrf2) were detected by Western blot.Results One month after TBI compared with the sham group,the escape latency (EL) ((35.31 ± 13.23)s vs (8.79±9.71)s) was prolonged and the target quadrant stay time ((17.78±4.68)s vs (26.35± 5.83)s) was shortened,the number of crossing platforms ((1.40±1.75) vs (3.50±1.45)) decreased,the relative content of Aβ1-42 in hippocampus ((1.0140±0.0328) vs (0.4355±0.0152)) increased the relative content of tau protein ((0.8039±0.0251) vs (0.5170±0.0185)) increased,and Nrf2 expression levels ((0.3851±0.0188) vs (0.4901±± 0.0140)) decreased significantly,and the differences were statistically significant (t=5.110,3.625,4.068,16.010,9.208,4.474,all P<0.01);Compared with TBI group,EL ((23.74±10.95) vs (35.31±13.23)) shortened,target quadrant dwell time ((24.28±5.37) vs (17.78±± 4.68)) shortened,the number of crossing platforms ((3.30±1.88) vs (1.40±1.75)) decreased,and the relative content of Aβ1-42 in hippocampus ((0.8370±0.0188) vs (1.0140±0.0328)) significantly decreased,the relative content of tau protein ((0.6693±0.0166) vs (0.8039±0.0251)) significantly decreased,and the expression level of Nrf2 ((0.4738 ± 0.0166) vs (0.3851 ± 0.0188)) significantly increased,and the differences were statistically significance (t=2.052,2.866,5.196,4.693,3.480,3.538,all P<0.01).Conclusion Exendin-4 can significantly improve the learning and memory function of TBI rats,increase the expression of Nrf2,decrease the content of Aβ1-42 and tau in hippocampus,and improve the prognosis of neurological function of TBI rats.