电针调节RIP1/RIP3/MLKL通路对脑缺血再灌注损伤大鼠神经元程序性坏死的影响OA北大核心CSTPCD

Objective To investigate the neuroprotective effect of electroacupuncture(EA)at"Quchi"(LI11)and"Zusanli"(ST36)in the rats with cerebral ischemia reperfusion injury and its influence on programmed necrosis of cerebral cortical neurons.Method Sixty male SD rats were randomly divided into sham-operation group,model group,EA group and inhibitor group,with 15 rats in each group.Left middle cerebral artery occlusion model was estab-lished using the modified thread embolism method.In the sham-operation group,the carotid artery was exposed and dissociated in each rat.EA was applied to"Quchi"(LI11)and"Zusanli"(ST36)on the right side for 30 min each time,once daily for 7 days in the rats of the EA group.The rats in the inhibitor group were intraperitoneally injected with norstatin-1(0.6 mg/kg)for consecutive 7 days.The neurological deficit score of rats in each group was observed.HE staining was adopted to detect the degree of pathological damage of the cerebral cortex in the infarction area.Using TUNEL staining,the apoptosis of cortical neurons in the infarction area was determined;the contents of tumor necrosis factor α(TNF-α),interleukin(IL)-1β and IL-6 were detected by ELISA;the mRNA and protein expression of the recep-tor interacting protein-1(RIP1),the receptor interacting protein-3(RIP3)and the substrate mixed lineage kinase like protein(MLKL)were detected by fluorescence quantitative PCR and Western blot,respectively.Results In compari-son with the sham-operation group,the neurological deficit score in the model group was higher(P<0.01);HE staining showed that there was the pathological damage in the infarction area;the neuron apoptosis rate,the contents of TNF-α,IL-1β and IL-6,and the mRNA and protein expressions of RIP1,RIP3 and MLKL increased(P<0.01)in the model group.In the EA group,the neurological deficit score was reduced(P<0.01);HE staining showed that the pathological damage was ameliorated in the infarction area;the neuron apoptosis rate,the contents of TNF-α,IL-1β and IL-6,and the mRNA and protein expressions of RIP1,RIP3,MLKL decreased(P<0.05,P<0.01)when compared with those in the model group.Conclusion EA can attenuate cerebral ischemia reperfusion injury and display its neuroprotective effect probably through inhibiting programmed necrosis of cerebral cortical neurons in the rats.