Regulatory Role Of MKP-1on The Arginine Metabolism Pathway After TBI

Objective: To observe the morphological changes of brain aftertraumatic brain injury (TBI), measure urea and NO content inpericontusional cerebral cortex, and detect MKP-1，arginaseⅠ，eNOS andMAPKs signaling changes, discuss regulatory role and molecularmechanism of MKP-1on the arginine metabolism pathway.Methods:1. Age, body and weight matched male rats used to constructthe Feeney’s TBI rat model.2. HE staining was performed to observemorphological changes after TBI.3. Urea and NO detection kits were usedto measure the urea and NO content in pericontusional cerebral cortexbetween control group and TBI group.4. Distribution and expression ofMKP-1and arginaseⅠ were detected by immunohistochemistry.5. WesternBlot were performed to detect expression level of MKP-1, eNOS,arginaseⅠ and MAPKs signaling in pericontusional cerebral cortex.Results: After TBI, HE staining showed that the brain tissue hadischemic changes. The space around the neurons and capillaries becamelarger, some of the neurons showed swlling. Concentration of urea graduallyincreased along with the injury time extendence, and reached its peak at24h and then decline to72h. Concentration of NO significantly decreased to3hand then slightly increased to72h, which was below to the level of thecontrol after TBI. The results of IHC showed that the positive expression ofMKP-1was widely distributed in neurons in the brain cortex andhypothalamus. The positive staining cells increased in pericontusionalcerebral cortex significantly at3h and6h, and partly positive staining cellswere distributed around the blood vessels. The positive expression ofarginaseⅠwere widely distributed in cytoplasm of neurons in the braincortex, hippocampus and hypothalamus. The positive staining cells slightlydecreased in pericontusional cerebral cortex with plenty of positive stainingcells distributed around the blood vessels. The level of MKP-1wasup-regulated by3h after TBI, and reached peak at6h with increasing level tonormal at24h. The level of eNOS were down-regulated by3h after TBI, andreached peak at6h with decreasing level to normal at24h. The level ofarginase-1were no changes from3h to24h, but significantly decreased at72h. pERK and pp38MAPK expression level significantly down-regulatedwith pJNK level intact.Conclusion: Pathological factors induced MKP-1expressionup-regulated in pericontusional cerebral cortex after TBI, which specificallydecreased the expression level of pERK and pp38MAPK with the pJNKintact to regulate the arginine metabolism by inhibiting the expression ofeNOS and facilitating the expression of arginaseⅠ. The decreased NO content and increased urea level attributed to the defect of cerebral bloodflow and formation of brain edema. MPK-1may be a new target for thetreatment of TBI.