The Physiological Levels Of Androgen's Protective Effect On Focal Cerebral Ischemia In Male Rats

Objective :Our topic is to study the protective mechanism of physiological levels of androgen after focal cerebral ischemia of orchiectomized rats on the expression of NF-κB,caspase-3,MDA,SOD and so on. Then to established the oretical basis for the view of androgen treatment of cerebrovascular disease.Methods:In this study,we selected 96 healthy male Sprague-Dawley rats, which were randomly divided into three groups: sham operation group(N=32), orchiectomized group(ORX)(N=32),sham orchiectomized group(SORX)(N=32), Each group was further divided into 4 subgroups respectively according to 6 h,24 h,48 h and 72 h after model creation,each group has 8 rats. We product model of male rats castration and middle cerebral artery occlusion (MCAO) to simulation of clinical patients with ischemic cerebrovascular disease. The middle cerebral artery oclusion (MCAO) model was made after orchiectomized 2 weeks. Sham operation group only isolated carotid artery, not embolizate middle cerebral artery. Sham orchiectomized group only cut testicular capsule, not castrated。In the corresponding time points after the success of manufacturing model, each group rats'neurological deficit score were tested, Brain water content was detected by dry-wet weight method. the levels of NF-κB p65,caspase-3 were detectived byImmuno histochemistry technology. The contents of MDA and SOD were determined separately by thiobarbituric acid method and xanthine oxidase method; We adopted SPSS13.0 software to carry out statistics analysis. The differences of groups were analyzed by t-tests and ANOVA.Results:1. Neurological deficit score: ORX groups'score were significantly higher than SORX group in each detected time(P<0.05).2. Brain water content: the brain water content of sham groups had little changes in every detected time points, compared to sham groups, SORX groups'brain water content began to consistently rise from 6 hours, and got its peak at 72 hour post- Ischemia. the changing trend of brain water content of ORX groups'was same as SORX groups', but all higher in each detected time points except 6h. The brain water content of ORX groups were significantly higher than SORX group(P<0.05).3. NF-κB p65 and caspase-3 expression were detected by immunohistochemistry mothod: Ischemic brain tissue in sham operation group have very little expression of NF-KB p65, the ORX group have little NF-κB p65 expression after 6h, increased and got its peak at 24h post- ischemia, then descented, but still in high expression at the 72h points. the changing trend of NF-KB p65 expression in ORX group was same as SORX groups, but all higher in each detected time point. There was statistically significant difference between the ORX group,SORX group and the sham operation group. (p<0.01), There was statistically significant difference between the ORX group and the SORX group (p<0.05). The changing trend of caspase-3 expression was same as NF-KB p65 in each group. There was also statistically significant difference between the ORX group and the SORX group (p<0.05).4. The contents of SOD and MDA: In ORX group, the contents of SOD had significant increased at 6h in brain tissue, then decreased and got its peak at 24 hour post- ischemia , the SORX group had the same change with the ORX group, but all higher in each detected time points. There was statistically significant difference between the ORX group,SORX group and the sham operation group. (p<0.01),There was statistically significant difference between the ORX group and the SORX group (p<0.05); in ORX group, the the contents of MDA had little expression at 6h in brain tissue, the expression increased significantly in 24-48h, and got its peak at 72 hour post- ischemia. the SORX group had the same change with the ORX group, but all lower in each detected time points. There was statistically significant difference between the ORX group,SORX group and the sham operation group. (p<0.01),There was statistically significant difference between the ORX group and the SORX group (p<0.05).Conclusion:1. Physiological levels of androgen can reduce rat neurologic deficits degree and cerebral edema degree after cerebral ischemia.2. Physiological levels of androgen could block the NF-κB p65 activation and reduce the caspase-3 expression, could reduce the brain tissue inflammation and reduce the cell apoptosis in ischemic penumbra after cerebral ischemia.3. Physiological levels of androgen could reduced the content of MDA and raised the expression of SOD in the brain ischemia area, and had an obviously protective effect on neuronal injury after ischemia.