Mechanism of Neuroprotective Effect of Dexmedetomidine on Hypoxic-ischemic Brain Injury in Neonatal Mice

WU Xiaojun; WANG Rixing; LIN Fangchong; LYU Youkai; FENG Qitao; YUN Tianqi

doi:10.3969/j.issn.2095-3097.2023.06.001

Abstract：Objective To investigate the neuroprotective effect of Dexmedetomidine(Dex)on hypoxic-ischemic brain injury(HIBD)in neonatal mice and its mechanism.Methods C57BL/6 neonatal mice(n =70)were randomly divid-ed into Sham operation group(Sham group,n =10),model group[hypoxic-ischemia(HI)group,n =10]and Dex treat-ment group(HI +Dex group,n =10),HI +NS-siRNA group(n =10),HI + PPARγ-siRNA group(n =10),HI + Dex + NS-siRNA group(n =10),and HI +Dex +PPARγ-siRNA group(n =10).HIBD models of neonatal mice were constructed in all groups except the Sham group,and the HI +Dex group was intraperitoneally injected with 0.1 mg/kg Dex.The learning and memory ability of mice in Sham group,HI group and HI +Dex group was determined by Morris water maze test.The vol-ume of cerebral infarction was detected by 2,3,5-triphenyltetrazolium chloride(TTC)staining,the apoptosis of brain tissue cells was detected by TUNEL staining,and the level of reactive oxygen species(ROS)was detected.Western blotting was used to detect the protein expressions of Bax,cleaved caspase-3,Bcl-2,SOD2,peroxissome proliferator-activated receptor(PPARγ),and signal transduction and transcriptional activator 3(STAT3)in brain tissue.The effect of Dex on the expres-sion of SOD2 protein through PPARγ/STAT3 pathway was analyzed.Results Compared with Sham group,the volume of cer-ebral infarction in HI group was increased,the escape latency was prolonged,and the percentage of swimming time in the plat-form quadrant was decreased.The number of apoptotic cells in brain tissue and the expression of Bax and cleaved caspase-3 protein were increased,the expression of Bcl-2 protein was decreased,the ROS level was increased,and the level of SOD2 protein were decreased;the expression levels of p-PPARγ and p-STAT3 protein were decreased(P<0.01).Compared with HI group,after Dex treatment,the volume of cerebral infarction was decreased,the escape latency was shortened,and the percentage of swimming time in the platform quadrant was increased.The number of apoptotic cells in brain tissue as well as the expression of Bax and cleaved caspase-3 protein was decreased,while the expression of Bcl-2 protein was increased;the ROS level was decreased,while the level of SOD2 protein and the levels of p-PPARγ and p-STAT3 protein were increased(P<0.01).Compared with HI + NS-siRNA group,p-PPARγ,p-STAT3 and SOD2 protein levels in HI + Dex + NS-siRNA group were increased,while p-PPARγ protein levels in HI + PPARγ-siRNA group were decreased(P<0.01).Compared with HI + Dex + NS-siRNA group,the levels of p-PPARγ,p-STAT3 and SOD2 protein in HI + Dex + PPARγ-siRNA group were decreased(P<0.01).Conclusion Dex can reduce oxidative stress injury and inhibit cell apoptosis of neonatal HIBD mice by regulating PPARγ/STAT3 pathway,thus playing a neuroprotective role.