| Objective:To evaluate the effects of different time courses of Mild Therapeutic Hypothermia(MTH)on Cerebral ischemia-reperfusion injury(CIRI)in rats,By comparing MTH treatments given at different time points after cerebral ischemia in rats.Observing the effects on cerebral ischemia reperfusion injury in rats,Providing a theoretical basis for clinically MTH in the treatment time window of CIRI.Methods:72 healthy adult male SD rats weighing 250～300g were randomly divided into 6groups(n=12): sham operation group(S group),cerebral ischemia reperfusion injury group(IR Group),immediate therapeutic mild hypothermia group after ischemia(MTH1 group),immediate therapeutic mild hypothermia group after ischemiareperfusion(MTH2 group),therapeutic mild hypothermia group 1h after reperfusion(MTH3 group)and 2h after reperfusion Therapeutic mild hypothermia group(MTH4group).The IR group,MTH1 group,MTH2 group,MTH3 group,and MTH4 group were treated with a suture method for 2h reperfusion of cerebral ischemia in rats to prepare CIRI models,and no suture was placed in the S group.S group and IR group were placed at room temperature,MTH1 group,MTH2 group,MTH3 group and MTH4 group were respectively treated immediately after cerebral ischemia,immediately after ischemia-reperfusion,1h after reperfusion,and 2h after reperfusion,MTH treatment was performed at low temperature and maintain for 4h.Modified Neurological Severity Scores(m NSS scores)were performed 24 hours after reperfusion.After the behavioral test,the rat brain tissues were taken,and 2,3,5-(Triphenyltetrazolium chloride,TTC)was used,stain and detect cerebral infarction volume,TUNEL method to detect neuronal apoptosis,chemical colorimetric method to detect brain tissue superoxide dismutase(SOD)and malondialdehyde(MDA)activity,Elisa method measured the levels of Tumor necrosis factor-α(TNF-α)and interleukin-6(IL-6)in brain tissue.Western-blot method detects protein expression of Caspase-3,Bax,and B-cell lymphoma-2(Bcl-2)Caspase-3 in brain tissue.Results:(1)Compared with the S group,the m NSS score,cerebral infarction volume and the percentage of infarct volume increased in the other 5 groups(P<0.05);Compared with the IR group,rats in the MTH1,MTH2,MTH3 and MTH4 groups m NSS score,cerebral infarction volume,and percentage of infarct volume all decreased(P<0.05);compared with MTH1 group,m NSS score,cerebral infarction volume,and percentage of infarct volume increased in MTH2,MTH3,and MTH4 groups(P<0.05));Compared with the MTH2 group,the NSS score,cerebral infarction volume and infarct volume percentage of rats in the MTH3 and MTH4 groups all increased(P<0.05).(2)Compared with the S group,the MDA activity in the brain tissue of the other5 groups increased,while the SOD activity in the brain tissue decreased(P<0.05);compared with the IR group,the MTH1 group,MTH2 group,MTH3 group and MTH4 group rat brain Tissue MDA activity decreased,brain tissue SOD activity increased(P<0.05);compared with MTH1 group,MTH2 group,MTH3 group and MTH4 group rat brain tissue MDA activity increased,brain tissue SOD activity decreased(P<0.05);Compared with the MTH2 group,the activity of MDA in the brain tissue of rats in the MTH3 and MTH4 groups increased,and the activity of SOD in the brain tissue was decreased(P<0.05).(3)Compared with the S group,the brain tissue TNF-α and IL-6 levels of the other 5 groups increased(P<0.05);compared with the IR group,the MTH1,MTH2,MTH3,and MTH4 groups levels of TNF-α and IL-6 in brain tissue decreased(P<0.05);compared with the MTH1 group,the levels of TNF-α and IL-6 in the brain tissue of rats in the MTH2,MTH3 and MTH4 groups increased(P<0.05));Compared with the MTH2 group,the levels of TNF-α and IL-6 in the brain tissue of rats in the MTH3 and MTH4 groups were increased(P<0.05).(4)Compared with group S,the expression of neuronal apoptosis index,brain tissue Caspase-3 and Bax in the other 5 groups were increased,while the expression of brain tissue Bcl-2 was decreased(P<0.05).Compared with IR group,the neuronal apoptosis index and the expression of Caspase-3 and Bax in brain tissue of rats in MTH1,MTH2,MTH3 and MTH4 groups were decreased,while the expression of Bcl-2 in brain tissue was increased(P<0.05).Compared with MTH1 group,the neuronal apoptosis index,the expression of Caspase-3 and Bax in brain tissue of MTH2 group,MTH3 group and MTH4 group were increased,and the expression of Bcl-2 in brain tissue was decreased(P<0.05).Compared with MTH2 group,the neuronal apoptosis index,the expression of Caspase-3 and Bax in brain tissue of rats in MTH3 and MTH4 groups were increased,and the expression of Bcl-2 in brain tissue was decreased(P<0.05).Conclusion:Mild Therapeutic Hypothermia(MTH)can reduce cerebral ischemiareperfusion injury(CIRI)in rats,and the MTH treatment immediately performed after cerebral ischemia has the best effect. |
PDF Full Text Request