Aspirin Induce The Expression Of NGF And BFGF After Ischemia/reperfusion In Rats

Backgroung and purpose: Besides its promoting neuron growthand differentiation, regulating metabolism and function of nervoussystem,neurotrophic factor family(NTFs) play a important role in neuronreactivation and recovery after nervous system damage .NTF,as comparedwith ASA,have similar neuroprotective mechanism--- reducing excitatoryamino acid toxicity and free radical damage, inhibiting iNOS release andcell apoptosis ,regulating glycometabolism, stabilizing intra-cellular Ca2+density, degrade vascular resistance after Ischemia/Reperfusion(CI/RP),et al. Apart from its preventive actions against stroke due to itsantithrombotic properties, recent data in the literature suggest that ASAalso exert direct neuroprotective effects by inhibiting excitatory amino acidrelease, NF-kappaB translocation to the nucleus,inducing nitric oxidesynthase (iNOS) expression , decreasing of brain ATP levels, production offree radical and inflammatory and facilitating neuron nitric oxidesynthase(nNOS) expression and Bcl-2/Bax. The mechanism of ASA and NTFs have many similaraspects,taking effects on excitatory amino acid , free radical ,energymetabolism,apoptosis and nitric oxide.However , little research of theeffect of ASA to the expression of NTFs have been reported. Thus,ourpurpose ,through observing the ASA' s contribution to the neurologicfunction,brain infarct volume and the expression of Nerve GrowthFactor(NGF) and basic Fibroblast Growth Factor(bFGF) ,is to probe themechanism of ASA neuroprotective effect. Methods: Established the rat MCA cerebral ischemia/reperfusion(CI/RP)model with suture occlusion technique and then the rats wereevaluated with reformed Bederson measuring scale. We establish five timedots(6hour,1day,2day,4day and 7day),and set up experiment group andcontrast group on each time dots. The rats of 1～3 score was selected intothe ten groups and were evaluated with reformed Bederson measuring scaleevery morning after CI/RP.And at the same time,the experiment groupswere intraperitoneal injected with ASA80 mg·kg –1as intervention factorand the contrast group was given the same volume menstruum.The firstinject was given just after CI/RP,and the first evaluation was at two hoursafter CI/RP.Every laboratory animal was perfused withparaformaldehyde,taken brain and detected the expression of NGF andbFGF with immunhistochemistry on its corresponding time dot,except forsix rats selected randomly from seven day time dot group which were takenout for TTC staining. Result: Comparing with contrast group,the Bederson measuringscale of experiment group was conspicuously reduced and have statisticalsignificance(p﹤0.05) during four day to seven day after CI/RP and thedisparation became very significantly in seven day after CI/RP.The infarctvolume of experiment group deflated in sevebn day after CI/RP ,and havesignificant disparation with contrast group(p ﹤ 0.05). Application ofASA,the peak time of NGF expression in neuron bring forward from fourday to one day and had significant disparation between experiment groupand contrast group; the peak time of bFGF expression in neuron advancedfrom 2d ～ 4d to 6h ～ 1d,and hadn't decrease obviously.Significantdisparation of NGF expression had not found in glia cell;but with regard tobFGF,glia cell with ASA can raise up the second peak(p﹤0.05) which wasat four day after CI/RP,and the peak time was lengthened beyond seven dayafter CI/RP. Conclusion: 1.Application of ASA after CI/RP can reduce infarctvolume and decrease neurologic impairment; 2.Application of ASA afterCI/RP can increase expression of endogenous NGF and bFGF after CI/RPin brain,and this effect can be observed early after CI/RP and retain for atlest one week;3.The mechanism of neuroprotective effect of ASA maybepartly due to its effect of inducing the expression of NTFs after CI/RP.