Blocking ERK signaling pathway lowers MMP-9 expression to alleviate brain edema after traumatic brain injury in rats / 浙江大学学报·医学版
Journal of Zhejiang University. Medical sciences
; (6): 1018-1022, 2020.
Article
ي Zh
| WPRIM
| ID: wpr-828505
المكتبة المسؤولة:
WPRO
ABSTRACT
OBJECTIVE@#To investigate the effects of blocking the activation of ERK pathway on the expression of matrix metalloproteinase-9 (MMP-9) and the formation of cerebral edema in SD rats after brain injury.@*METHODS@#Ninety SD rats were randomly divided into 3 equal groups, including a sham-operated group, modified Feeney's traumatic brain injury model group, and ERK inhibition group where the ERK inhibitor SCH772984 (500 μg/kg) was injected via the femoral vein 15 min before brain trauma. At 2 h and 2 days after brain trauma, the permeability of blood-brain barrier was assessed by Evans blue method, the water content of the brain tissue was determined, and the phosphorylation level of ERK and the expression level of MMP-9 mRNA and protein were measured by RT-PCR and Western blotting.@*RESULTS@#Compared with the sham-operated group, the rats with brain trauma exhibited significantly increased level of ERK phosphorylation at 2 h and significantly increased expression of MMP-9 mRNA and protein 2 days after the injury ( < 0.01). Treatment with the ERK inhibitor significantly decreased the phosphorylation level of ERK after the injury ( < 0.01), suppressed over-expression of MMP-9 mRNA and protein 2 days after the injury ( < 0.01). The permeability of blood-brain barrier increased significantly 2 h after brain trauma ( < 0.05) and increased further at 2 days ( < 0.01); the water content of the brain did not change significantly at 2 h ( > 0.05) but increased significantly 2 d after the injury ( < 0.01). Treatment with the ERK inhibitor significantly lowered the permeability of blood-brain barrier and brain water content after brain trauma ( < 0.01).@*CONCLUSIONS@#Blocking the activation of ERK pathway significantly reduced the over-expression of MMP-9 and alleviates the damage of blood-brain barrier and traumatic brain edema, suggesting that ERK signaling pathway plays an important role in traumatic brain edema by regulating the expression of MMP-9.
النص الكامل:
1
الفهرس:
WPRIM
الموضوع الرئيسي:
Pharmacology
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Piperazines
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Brain Edema
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Random Allocation
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Gene Expression Regulation, Enzymologic
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Rats, Sprague-Dawley
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Matrix Metalloproteinase 9
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MAP Kinase Signaling System
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Therapeutic Uses
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Protein Kinase Inhibitors
المحددات:
Animals
اللغة:
Zh
مجلة:
Journal of Zhejiang University. Medical sciences
السنة:
2020
نوع:
Article