Objective To investigate the effect of exogenous kallikrein on apoptosis of the neurons aroundthe cerebralinfarctareain rats. Methods Thirty rats wjth cerebral infarction induced by middle cerebral artery occlusion(MCAO)were assigned randomly into 3 groups(n=10),namely the blank control group,saline group,and pAdCMV-HTK group.In the pAdCMV-HTK group,kallikrein gene was delivered into the cerebral ischemie lesion via a replication-defective adenovims using stereotaetic injection technique, and the expression of exogenous kallikrein was detected immunohistoehemically.TUNEL staining was performed to evaluate the neuronal apoptosis around the infarct area,and RT-PCR used to detect the mRNA expressions ofbcl-2,bax and caspase-3 in the brain tissues. Results At 24 h aftertreatment there were some HTK expressed cells found in group C and peal(at 72 h after treatment.While compare with group B and group C,there existed significant difference(112±6.1,68±4.2,59±3.9,P<0.05).At 72 h after treatment,the NSS of group C was significantly lower than that ofgruop B and A(6.70±0.16,8.13±0.16,7.93±0.20,P<0.05);7 days after the treatment,the difference was more significant(5.14±0.18,7.82±0.14,7.91±0.10,P<0.01).Apoptotic cells were mostly seen around the infarct area.The ratsinpAdCMV-HTK group showed significantly reduced number of cells positive for TUNEL staining as compared to those in the saline and blank control groups at 3 days(10.1±0.9,16.7±1.1,and 20.4±0.8,respectively)and 7 days after the treatment(15.2±1.2,33.6±1.3,and 28.8±1.7,respectively)(P<0.05).The mRNA levels ofbc1-2.bax and caspasc-3 were elevated in all the groups at 24 h,peaked at 72 h,and decreased gradually till 7 days alter the treatment.Compared with those in the other two groups，bcl-2 mRNA level in the pAdCMV-HTK group increased slightly P>0.05) while bax and caspase-3 mRNA levels decreased markedly(P<0.05) 72 h and 7 days after the treatment.Conclusion Kallikrein can inhibit neuronal apoptosis around the cerebral infarct and improve the neurological fimction of rats following cerebral infarction probably by reducing the expressions of such apoptotic factors as bax and caspase-3.

Objective To analyze the gene expression profiling in the periinfarct cortex in the late stage after stroke onset in renovascular hypertensive rats (RHRs) with gene chip technology.Methods RHRs were induced by the method of Goldblatt's 2k2c operation. Cerebral infarction was also induced by permanent middle cerebral artery occlusion (pMCAO) in RHRs. Sham-operated group was established as controls. Total RNA was extracted from the perinfarct cerebral cortex in injured hemisphere 7 d after pMCAO, and the RNA was performed fluorescence labeling, followed by hybridization with 5705 oligo chips. And then, scanning was performed; the data was collected and chosen for microarray analysis using oligonucleotide arrays. Resuits In total, 197 genes were expressed differentially, including 174 genes up-regulated expression and 23 genes down-regulated expression. The up-regulated genes were distributed among all 12 functional categories; the down-regulated genes were distributed only in the categories of transport, transcription regulator, signal,response to stress, metabolism and cell adhesion. Among the 12 functional categories, only 17differentially expressed genes were not previously reported to be associated with brain ischemia/infarction. Conelusion Active gene expression at late stage of cerebral infarction may imply the molecular mechanisms of injury or repair, being the targets of therapeutic intervention.