Study On The Protective Mechanism Of CART Threatment On Cerebral Ischemia-Reperfusion Injury

Object:To investigate the mechanism of cocaine-and amphetamine-regulated transcript peptides(CART)on neuroprotection after cerebral ischemia-reperfusion injury.Method:All 288 ealthy male Kunming white mice,10 to 12 weeks of age,were randomly divided into four groups:ischemia-reperfusion group(I/R group,n=81),I/R+CART group(n=81)and sham-operation group(sham group,n=63),sham+CART group(n=63).The model that middle cerebral artery occlusion(MCAO)2 h,reperfusion 24 h,72 h and 7 d was estabilished.Before reperfusion,CART55-102(0.5 jig,repeat every 24 h)injection and equivalent CART were injected via tail vein in sham+CART group.TTC assay examined cerebral infarction volume.The transmission electron microscope(TEM)was used to detect the changes of synaptic ultrastructure at different time points and the expression of postsynaptic density 95(PSD-95)were quantitatively analyzed by West blot at reperfusion 72 h.Result:(1)Compared with sham-operation group,the number of synapses was significantly decreased[(3.37±0.38)num/μm2 vs(7.04±0.55)num/μm2,(2.89±0.22)num/μm2 vs(6.89±0.04)num/μm2,(3.25±0.18)num/μm2 vs(6.78±0.42)num/μm2;all P<0.05],the density of PSD was significantly decreased[(24.4±2.8)nm vs(47.3±6.1)nm,(23.8±3.7)nm vs(46.5±7.5)nm,(24.6±2.2)nm vs(48.1±5.1)nm;all P<0.05],the width of synaptic space was increased[(25.2±2.1)nm vs(21.54±1.63)nm,(25.2±1.4)nm vs(21.3±1.0)nm,(23.7±2.6)nm vs(21.6±1.6)nm;all P<0.05]at different time points and the expression of PSD-95 protein was decreased(P<0.05)at reperfusion 72 h in ischemia-reperfusion group.(2)Compared with the ischemia-reperfusion group,the infarction volumes in the CART group were significantly lower than that in the I/R group[(29.0±1.9)%vs(36.3±1.4)%,(38.1±1.4)%vs(47.6±2.7)%,(36.0±2.8)%vs(42.5±2.0)%,respectively;all P<0.05].There was a significant increase in the number of synapses[(4.322±0.35)num 个/μm2]and the expression of PSD-95 at reperfusion 72 h(P<0.05);the PSD density thickening[(33.8±3.4),(34.2±4.6),(38.2±4.0)nm]was increased at different time points(P<0.05);but there was no significant difference in the synaptic gap width at each time point(P>0.05)in CART group.Conclusion:CART treatment can regulation of synaptic plasticity and reduced cerebral infarction volume in ischemia reperfusion mice.