Preventive and therapeutic effects of resveratrol alone or in combination with miR-27b agonist on secondary pathological injury of brain tissues in rats with ICH
Objective To observe the preventive and therapeutic effects of resveratrol(Res)alone or in combina-tion with miR-27b agonist on secondary pathological injury of brain tissues in rats with intracerebral hemorrhage(ICH).Methods Totally 180 male SD rats were randomly divided into the sham-operated group,the ICH group,the Res group,the Res+miR-27b agomir group,and the NC group,with 36 rats in each group.The rats in the ICH group,the Res group,the Res+miR-27b agomir group,and the NC group were used to establish the ICH models by collagenase injection of the caudate nucleus method.Rats in the Res,Res+miR-27b agomir,and NC groups were injected intraperitoneally with Res for 7 consecutive days before modeling,while rats in the sham-operated and ICH groups were injected with an equal vol-ume of DMSO.Rats in the Res+miR-27b agomir group were injected with the miR-27b agomir into the right ventricle of the rats for 3 d before modeling,while rats in the NC group were injected with agomir-negative control reagents.And rats in the sham operation,ICH,and Res groups were injected with equal volume of normal saline.After successful modeling,the rats in each group continued to receive feedings for 24 h.Neurological function was assessed by using the mNSS scor-ing scale.The brain tissues of rats in each group were taken after execution,and the apoptosis rate of neuronal cells in the brain tissues was measured by TUNEL method,while inflammatory factors and oxidative stress-related factors in the brain tissues of rats were detected by ELISA.Besides,qRT-PCR was used for the detection of miR-27b and nuclear factor-relat-ed factor 2(Nrf2)mRNA in the brain tissues of rats.Western blotting was used to detect the Nrf2/ARE signaling pathway-related proteins Nrf2,heme oxygenase(HO-1),and quinone oxidoreductase 1(Nqo1)in the brain tissues of rats.Re-sults The mNSS score,neuronal apoptosis rate of brain tissue,and the expression levels of TNF-α,IL-1β,and MDA in the sham-operated group were lower than those in the rest of the groups(all P<0.05),and the SOD activity was higher than those in the rest of groups(all P<0.05).The rat mNSS score,brain tissue neuronal cell apoptosis rate,and the ex-pression levels of TNF-α,IL-1β,and MDA were higher in the ICH group than in the rest of groups(all P<0.05),and the SOD activity was lower than the rest of the groups(all P<0.05).Moreover,the mNSS score,apoptosis rate of neuronal cells in the brain tissue and the expression levels of TNF-α,IL-1β and MDA were higher in the Res+miR-27b agomir group than in the Res group and the NC group(all P<0.05),while the SOD vitality was lower than those in the Res group and the NC group(all P<0.05).Compared with the sham-operated group,the relative expression of miR-27b decreased in the brain tissues of rats in the ICH group,the Res group,the Res+miR-27b agomir group,and the NC group,whereas the relative expression of Nrf2 mRNA and protein,HO-1 protein,and NQO1 protein increased(all P<0.05).In comparison with the ICH group,the relative expression of miR-27b in the brain tissues of rats in the Res group,the Res+miR-27b agomir group,and the NC group decreased,while the relative expression of Nrf2 mRNA and protein,HO-1 protein,and NQO1 protein all increased(all P<0.05).Compared with the Res+miR-27b agomir group,the relative expression of miR-27b decreased,while the relative expression levels of Nrf2 mRNA and protein,HO-1 protein,and NQO1 protein were ele-vated in the brain tissues of the rats in the Res group and the NC group(all P<0.05).Conclusion Res alone or in com-bination with miR-27b agomir has preventive effect on secondary pathological damage of brain tissue in rats with intracere-bral hemorrhage,and this effect may be associated with the activation of the Nrf2/ARE signaling pathway.