Adenosine preconditioning inhibits endoplasmic reticulum stress and protects against cerebral ischemia-reperfusion injury in rats
Objective To study the effect of pretreatment with adenosine on the expression of endoplasmic reticulum stress(ERS)glucose-regulated protein 78(GRP78),C/EBP homologous protein(CHOP)and tumor necrosis factor-α(TNF-α),interleukin-6(IL-6),IL-1β and nuclear factor kappa-B(NF-κB)after cerebral ischemia reperfusion injury(CIRI)in rats,in order to investigate the neuroprotective effect of adenosine on CIRI.Methods Thirty-six healthy male Srague Dawley(SD)rats weighing 250-280 g were randomly divided into three groups and 12 rats in each group:sham group,ischemia reperfusion(I/R)group,and adenosine preconditioning(AP)group.The rat model of middle cerebral artery occlusion(MCAO)was established by thread embolization.In AP group,2 mL of adenosine was injected intraperitoneally at 1.5 mg/kg body weight 3 days before making model,once a day for 3 days.The neurological severity score(NSS)was measured after 2 h of embolization.After 24 h of reperfusion,the rats were killed and the brains were harvested.TTC stent method was used to observe the infarct volume of the rat's brain.The mRNA expression of GRP78 and CHOP was detected by RT-qPCR.The expression of TNF-α,IL-6 and IL-1β in brain tissue were measured by ELISA and Western blot was used to measure the expression of NF-κB protein.Results The expression levels of NSS,GRP78 mRNA,CHOP mRNA,TNF-α,IL-6,IL-1β,IκB protein and p65 protein in brain tissue of rats in I/R model group were higher than those in sham group(all P＜0.05);The infarct volume and NSS in AP group were lower than those in I/R model group(both P＜0.05).The expression levels of GRP78 mRNA,CHOP mRNA,TNF-α,IL-6,IL-1β,IκB protein and p65 protein in brain tissue in AP group were lower than those of I/R model group(P＜0.0 5).Conclusions AP can alleviate the secondary injury of nerve cells induced by I/R,and its mechanism may be related to the inhibition of ERS by adenosine.
brain infarctionbrain ischemiareperfusion injuryadenosineendoplasmic reticulum stressinflammationnuclear factor-kappa B
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