Effect of basic fibroblast growth factor and danshen on bcl-2 and p53 mRNA expression in the brain o

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BACKGROUND:Both animal experiments and clinical studies have shown that basic fibroblast growth factor(bFGF)and danshen(Salvia miltiorrhiza)can exhibit protective effects on ischemia-reperfusion cerebral injury.OBJECTIVE:To test whether bFGF and danshen can protect cerebral injury induced by exposure to repeated,high,positive acceleration(+Gz)in an animal model and to analyze the possible mechanisms.DESIGN,TIME AND SETTING:Randomized controlled animal study.The experiment was performed at the Research Center for Molecular Biology,Air-force General Hospital of Chinese PLA from April to August 2000.MATERIALS:A total of 20 clean grade,healthy,Sprague Dawley rats of both genders,weighing(200±15)g,were provided by our experimental animal center.Rats were randomly divided into 5 groups:the control group,+Gz exposure group,bFGF group,danshen group,and saline group,with 4 animals per group.bFGF(Beijing Bailuyuan Biotechnology Co.Ltd.)and danshen solution(Shanghai Zhongxi Pharmaceutical Co.Ltd.)were used.METHODS:All rats were fixed on a rotary arm of a centrifugal apparams(2 m in radius)with their heads oriented towards the center of the apparatus.Except for rats in the control group.the value of+Gz exposure was+14 Gz with an acceleration rate of 1.5 G/s.The peak force lasted for 45 seconds.+Gz exposure was performed three times with intervals of 30 minutes.Rats in the control group received the same+Gz procedure,but the G value was+1 Gz.Rats in bFGF group and danshen group were intraperitoneally injected with 100 μg/kg bFGF or 15 g/kg danshen solution,respectively,at 30 minutes prior to centrifugation and immediately after tentrifugation.Rats in saline group were injected with the same volume of saline.Six hours after exposure,rats were decapitated.One hemisphere was preserved in liquid nitrogen for RNA extraction and the other was processed for apoptosis detection.MAIN OUTCOME MEASURES:mRNA levels of bcl-2 and p53 were measured by semi-quantitative reverse-transcription polymerase chain reaction.Apoptotic cell death was detected by terminal deoxvnuleotidyl transferase-mediated dUTP nick end labeling.RESULTS:Changes in mRNA expression of bcl-2 and p53 and apoptotic cells were observed in rat brain six hours after repeated+Gz cxposurcs.bFGF and danshen were able block the changes of bcl-2 and p53 expression and inhibit apoptotic cell death.CONCLUSION:The data suggest that apoptosis and changes in bcl-2 and p53 expression in the rat brain can be induced by repeated+Gz exposures.Apoptosis is,therefore,one of the molecular mechanisms of brain damage induced by repeated+Gz exposures.bFGF and danshen were of the equal potency in preventing brain injury induced by repeated+Gz exposures.
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