Expression Of HIF-1 And MMP-2 In Perihematoma After Intracerebral Hemorrhage In Rats

Objective The present series of experiments were performed to difine the time course of increased HIF-1αand MMP-2 expression and the change of brain water content that occurs in perihematoma after ICH in rats and to study the relation between HIF-1αand MMP-2.Methods The ICH animal models were established by injecting 50μl of autologous blood into the right caudate putamen(CP).55 healthy SD rats were randomly divided into normal group(n=5),sham-operated group(n=25)and ICH model group(n=25).Rats were sacrificed at 6h, 24h,72 h and 7d,21d after operation,respectively.Brain water content was measured by the dry-wet method.The mRNA expression of HIF-1αand MMP-2 was detected by reverse transcription polymerase chain reaction(RT-PCR).Immunohistochemical technique was used to evaluate the protein expression of HIF-1αand MMP-2.The correlation of HIF-1αand MMP-2 mRNA and protein expression between different groups was compared by Pearson's correlation coefficient.The correlation of BWC and HIF-1αprotein or MMP-2 protein expression between different groups was compared by Pearson's correlation coefficient.Results1.There is no brain edema in the sham-operated group and normal group.BWC was increased at the 6 hours after ICH in the rats,the peak value appeared at 24 to 72 hours,and began to decline at 7 days,and then went back to normal level at 21 days.2.It was not found of the expression of HIF-1αmRNA and HIF-1αprotein positive cells in the brain of sham-operated group and normal group,with the expression of HIF-1αmRNA and lots of buffy positive cells in the model group.The peek value appeared at 24 to 72 hours in the model group.There was positive correlation between HIF-1αprotein expression and BWC(r=0.818,P＜0.001).3.It was not found of the expression of MMP-2mRNA and a few MMP-2 protein positive cells in the brain of sham-operated group and normal group,with the expression of MMP-2mRNA and lots of buffy positive cells in the model group.The peek value appeared at 24 to 72 hours in the model group.There was positive correlation between MMP-2 protein expression.and BWC(r=0.795,P＜0.001).4.There was positive correlation between HIF-1αmRNA expression and MMP-2mRNA expression by Pearson's correlation coefficient (r=0.588,P=0.002).5.There was positive correlation between HIF-1αprotein expression and MMP-2 protein expression by Pearson's correlation coefficient (r=0.765,P＜0.001).Conclusions1.It was probably that brain edema was correlation with the up-regulation of HIF-1αand MMP-2 in perihematoma after intracerebral hemorrhage in rats.2.There was a positive relation of HIF-1αexpression and MMP-2 expression,and HIF-1αmaybe have interaction with MMP-2 in perihematoma after intracerebral hemorrhage in rats.