C-Jun N-terminal kinase inhibitor SP600125 attenuates cerebral ischemia-reperfusion injury in rats by downregulating MMP-9 expression
10.3760/cma.j.cn115354-20191016-00598
- VernacularTitle:JNK抑制剂SP600125通过下调MMP-9的表达减轻大鼠脑缺血再灌注损伤
- Author:
Chenchen XU
1
;
Hao FU
;
Hongyan ZHU
;
Qiang MENG
Author Information
1. 昆明理工大学医学院，昆明 650093
- Keywords:
Cerebral ischemia-reperfusion injury;
C-Jun N-terminal kinase;
Matrix metalloproteinase-9;
Blood-brain barrier
- From:
Chinese Journal of Neuromedicine
2020;19(5):449-453
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To investigate the changes of c-Jun N-terminal kinase (JNK) and matrix metalloproteinase-9 (MMP-9) expressions after cerebral ischemia-reperfusion in rats and whether JNK inhibitor SP600125 can protect the cerebral ischemia-reperfusion injury by down-regulating the expression of MMP-9. Methods:Eighty-five adult male SD rats were divided into sham-operated group ( n=35), ischemia group ( n=35) and SP600125 group ( n=15). The middle cerebral artery occlusion models in rats of ischemia group and SP600125 group were established by thread embolism method, and reperfusion was performed one h after ischemia. Rats in the SP600125 group were injected with SP600125 solvent (being dissolved in 10% dimethyl sulfoxide with final concentration of 20 mmol/L) in the lateral ventricle 30 min before cerebral ischemia. At 48 h after reperfusion, neurological impairment scale scores, volume ratio of ischemic lesion, and moisture content of brain tissues in rats from each group were evaluated. The protein expression levels of phosphorylated (p)-JNK, JNK and MMP-9 in the ischemic cortex were detected by Western blotting in rats from the sham-operated group and ischemic group at 3, 6, 24 and 48 h after reperfusion, and in rats from SP600125 group at 48 h after reperfusion. Results:As compared with the sham-operated group, rats in the ischemia group had significantly decreased neurological impairment scale scores, and significantly increased infarction volume ratio and moisture content of brain tissues 48 h after reperfusion. At 24 and 48 h after reperfusion, the p-JNK/JNK values and MMP-9 protein level in the ischemia group were significantly increased as compared with those in the sham-operated group ( P<0.05). As compared with the ischemia group, at 48 h after reperfusion, rats in the SP600125 group had significantly increased neurological impairment scale scores, and significantly reduced volume ratio of ischemic lesion and moisture content of brain tissues, and significantly reduced p-JNK/JNK values and MMP-9 protein level in the ischemic cortex ( P<0.05). Conclusion:The expressions of JNK and MMP-9 are increased after cerebral ischemia-reperfusion, and the JNK inhibitor SP600125 may decrease MMP-9 expression to reduce the degrees of cerebral infarction after cerebral ischemia-reperfusion, thereby playing a role in brain protection.
