| Object:Acute cerebral ischemia was a major disease with high disability and high mortality that took huge economic burden and psychological pressure for individual,family,society At present,thrombolysis therapy was the most commonly and approved treatment in clinical practice and recombinant tissue plasminogen activator(rt-PA)was the only FDA-approved thrombolytic agent that aimed to restore the blood flow of ischemic region and recovered the neurological function.Although rt-PA thrombolysis has been used as a golden standard treatment for ischemic stroke,the limitation of thrombolysis time window increased the risk of brain edema and intracranial hemorrhagic transformation(HT),only a few patients benefit from thrombolysis therapy.Therefore,it was critical to develop effective therapy strategies to save majority of acute ischemic infraction patients who missed the best time of rt-PA thrombolysis therapy.To investigate the protective effect and mechanism of electroacupuncture therapy to extend therapeutic window in acute cerebral ischemia model of rats..Method:Adult Sprague-Dawley rats were randomly divided into 5 groups:sham group,cerebral ischemia group(CI),rt-PA group,electroacupuncture combined with rt-PA group(acupuncture group),Inhibitor combined with rt-PA group(medicine group),and rt-PA group,acupuncture group,medicine group were divided into 4 subgroup(3h,4.5h,6h,9h)based on different thrombolysis time.Rats in all groups except sham group were established acute cerebral ischemia model,recombinant tissue plasminogen activator(rt-PA)were used in intravenous thrombolysis therapy,EA+rt-PA group received acupuncture therapy by needling at Renzhong(GV26)and Neiguan(PC6),and Doxycycline which was used as a broad spectrum inhibitor to inhibit matrix metalloproteases to control with electroacupuncture treatment Results:The results showed that EA retreatment down-regulated the expression of inflammatory factors(IL-1?,TNF-?)and inhibited the overexpression of MMPs(MMP-9,MMP-2)after rt-PA thrombolysis treatment,illuminated the molecular mechanism of EA therapy of protecting the BBB structure and function integrity,neurological function deficit and infract volume.The study suggested that EA extended the rt-PA thrombolysis therapy time window via upregulated the expression of MMP-9 and MMP-2.Conclusion:(1)Rat neurological function score:Compared with the ischemic model group,the neurological function of the rats in the supernatant window thrombolysis(6h,9h,)changed to varying degrees,but thrombolysis in the time window(3h,4.5h),the improvement trend of neurological dysfunction was more significant and the thrombolytic therapy was effective(P<0.05).Acupuncture combined with thrombolysis group and western medicine combined with thrombolysis group could improve the neurological function score Acupuncture was better than western medicine(P<0.05),the difference was statistically significant.(2)Percentage of cerebral infarction volume in rats:Compared with ischemic model group,the infarct volume of rats in each group was increased to some extent in the time window(6h,9h)Thrombolysis(3h,4.5h),cerebral infarction was significant in rats,thrombolytic therapy was effective(P<0.05);acupuncture combined with thrombolysis group and western medicine combined with thrombolysis group can reduce the percentage of cerebral infarction volume,Acupuncture was better than western medicine(P<0.05),the difference was statistically significant.(3)Cerebral hemorrhage:Compared with the ischemic model group,the amount of cerebral hemorrhage in the rats in the super-window thrombolysis(6h,9h)increased to varying degrees,but in the time window(3h,4.5h),the amount of cerebral hemorrhage in rats was significantly decreased,thrombolytic therapy was effective(P<0.05);acupuncture combined with thrombolysis group and western medicine combined with thrombolysis group can reduce the amount of cerebral hemorrhage,Acupuncture was better than western medicine(P<0.05),the difference was statistically significant.(4)Blood-brain barrier permeability:Compared with the ischemic model group,the changes of blood-brain barrier permeability were increased in different groups of thrombolysis(6h,9h)the blood-brain barrier injury was significantly decreased in the time window,and the thrombolytic therapy was effective(P<0.05).The combination of acupuncture combined with thrombolysis group and western medicine combined with thrombolysis group(P<0.05).The difference was statistically significant(P<0.05),but the effect of acupuncture was better than that of western medicine.(5)Brain water content:Compared with the ischemic model group,the brain water content of the rats in the supernatant window thrombolysis(6h,9h)showed an increasing trend,but thrombolysis in the time window(P<0.05).Acupuncture combined with thrombolysis group and western medicine combined with thrombolysis group could reduce the brain water content of rats,but the effect of acupuncture was significant(P<0.05)(P<0.05),the difference was statistically significant.(6)The levels of IL-1?,TNF-?mRNA and protein in the brain tissue of the rats in each group were significantly higher than those in the control group(P<0.05)(P<0.05).The expression of IL-1? and TNF-amRNA and protein in the time window were significantly lower than those in the control group(P<0.05)(P<0.05).The acupuncture combined with thrombolysis group and western medicine combined with thrombolysis group could effectively inhibit the expression of IL-1?,TNF-amRNA and protein,but the curative effect was better than that of western medicine(P<0.05).The difference was statistically significant.(8)The expression of occluding and Claudin-5 in the brain tissue of rats in each group was significantly higher than that in the control group(P<0.05)(P<0.05).The expression of occludin and Claudin-5 was significantly increased in thrombolysis(3h,4.5h),and the thrombolytic therapy was effective(P<0.05)The expression of occludin and Claudin-5 was up-regulated by thrombolysis group and western medicine combined with thrombolysis group,but the curative effect was better than that of western medicine(P<0.05).The difference was statistically significant. |
PDF Full Text Request