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Objective To observe the effects of electroacupuncture on central inflammatory response and neurotransmitter release in rats with post stroke spasticity(PSS);To exploring the mechanism in treating PSS based on IL-6/JAK2/STAT3 signaling pathway.Methods Totally 30 male SD rats were randomly divided into sham-operation group,model group and electroacupuncture group,with 10 rats in each group.The PSS model was prepared by the method of suture and N-methyl-D-aspartic acid receptor injection into internal capsule.The rats in the electroacupuncture group were electroacupulated on the affected side of the body at"Quchi"and"Yanglingquan"for 30 min/d for consecutive 7 d.The sham-operation group and the model group were only fixed without any interventions.The Zea Longa neurological function score and the modified Ashworth muscle tension score were evaluated before and after treatment in each group;the pathological changes of the cortex on the ischemic side were observed by HE staining;the contents of interleukin-6(IL-6),tumor necrosis factor-α(TNF-α),and γ-aminobutyric acid(GABA)in cortex on the ischemic side were detected by ELISA;the content of glutamate(Glu)was detected by biochemical kit;Western blot was used to detect the expressions of tyrosine kinase 2(JAK2),p-JAK2,signal transduction and transcription activating factor 3(STAT3)and p-STAT3 protein in ischemic cortex;RT-PCR was used to detect the mRNA expressions of JAK2 and STAT3 in ischemic cortex.Results Compared with the sham-operation group,neurological function score and muscle tension score significantly increased in the model group(P<0.01),with disorganized neurons in cerebral cortex,nucleus accumbens,the contents of IL-6,TNF-α and Glu significantly increased,the content of GABA significantly decreased(P<0.01),and p-JAK2,p-STAT3 proteins and JAK2 and STAT3 mRNA expression significantly increased(P<0.01,P<0.05).Compared with the model group,the neurological function score and muscle tension score of rats in the electroacupuncture group were significantly decreased(P<0.05),the degree of neuronal damage in cerebral cortex was reduced,the cell contour was clear,the content of IL-6,TNF-α and Glu were significantly decreased,and the content of GABA significantly increased(P<0.05,P<0.01),p-JAK2,p-STAT3 protein and JAK2,STAT3 mRNA expression significantly decreased(P<0.01).Conclusion Electroacupuncture may alleviate central inflammatory response and improve limb spasticity of PSS model rats by inhibiting the IL-6/JAK2/STAT3 signaling pathway.
RESUMO
Objective To observe the effects of electroacupuncture on post-stroke spasticity(PSS)rats and the relationship between microglia polarization-mediated neuroinflammation and neurotransmitter glutamate(Glu)and γ-aminobutyric acid(GABA)in cerebral cortex;To investigate the possible mechanism of electroacupuncture to relieve PSS.Methods Male SD rats were randomly divided into sham-operation group,model group and electroacupuncture group,with 10 rats in each group.A rat model of PSS was prepared using suture method combined with internal capsule injection of NMDA receptor.The electroacupuncture group selected"Quchi"and"Yanglingquan"electroacupuncture for 30 minutes per day,for 7 days,the model group and the sham-operation group were fixed at the same time without intervention.Zea Longa neurological function score and modified Ashworth muscular tone score were evaluated,and electrophysiology was tested;kits were used to GABA,Glu,tumor necrosis factor-α(TNF-α)and interleukin-10(IL-10)content in ischemic cortex;Western blot was used to detect the expression of GABRA1 and GAD67 protein in ischemic cortex;The co-expression of ionized calcium-binding protein 1(Iba-1),inducible nitric oxide synthase(iNOS)and Arg-1 were detected by immunofluorescence staining.Results Compared with the sham-operation group,the neurological function score and muscle tone score of the model group rats significantly increased(P<0.01),and muscle tone significantly increased(P<0.01);the contents of GABA and IL-10 in ischemic cortex significantly decreased(P<0.01),and the contents of TNF-α and Glu significantly increased(P<0.01),Glu/GABA ratio increased(P<0.01),GABRA1 and GAD67 protein expression significantly decreased(P<0.01),the co-expression of Iba-1 and iNOS significantly increased(P<0.01),while the co-expression of Iba-1 and Arg-1 was significantly decreased(P<0.01).Compared with the model group,the nerve function score and muscle tone score of the electroacupuncture group rats were significantly reduced(P<0.05),and muscle tone was significantly reduced(P<0.01);the contents of GABA and IL-10 in ischemic cortex significantly increased(P<0.01),and the contents of TNF-α and Glu significantly decreased(P<0.01),Glu/GABA ratio decreased(P<0.01),the protein expressions of GABRA1 and GAD67 significantly increased(P<0.01),the co-expression of Iba-1 and iNOS significantly decreased(P<0.01),while the co-expression of Iba-1 and Arg-1 significantly increased(P<0.05).Conclusion Electroacupuncture can effectively alleviate PSS,and its mechanism of action may be related to electroacupuncture regulating microglia polarization and reduing neuroinflammation.
RESUMO
Objective:To observe the effects of electroacupuncture on the expression of cortical solute carrier family 7 member 11(SLC7A11),glutathione(GSH)and glutathione peroxidase 4(GPX4)in rats with post stroke spasticity(PSS),and to explore the mechanism of electroacupuncture in the treatment ferrozosis in PSS.Methods:Thirty SD male rats were randomly divided into sham group,model group and electroacupuncture group.A modified Zea-Longa wire bolus+internal capsule injection NMDA method was used to produce a rat model of PSS.In the electroacupunc-ture group,the affected side of Yanglingquan and Quchi were needled once/day for 30 min/time for 7 d.In the sham group and the model group,only fixation without intervention was performed during the same period.Zea-Longa Neuro-logical Function Score was used to detect the neurological function of rats,electrophysiological tracing method was used to detect the muscle tone of rat quadriceps,Western Blot was used to detect the protein expression of rat cortical SLC7A11 and GPX4,Enzyme-linked immunosorbent assay(ELISA)was used to detect the GSH content of rat cortex,and real time RT-PCR was used to detect the mRNA of rat cortical SLC7A11 and GPX4 mRNA expression.Results:Neurological function scores were elevated;quadriceps muscle tone was increased;GSH content was decreased;the protein expression of SLC7A11 and GPX4 was significantly decreased;the expression of SLC7A11 mRNA and GPX4 mRNA was significantly decreased.Electroacupuncture treatment resulted in lower neurological function scores,lower quadriceps muscle tone,increased GSH content in rat cortex,significantly up-regulated protein expression of SLC7A11 and GPX4,and significantly increased expression of SLC7A11 and GPX4 mRNA.Conclusion:Electroacupuncture on"Yanglingquan"and"Quchi"could improve limb spasticity and promote the recovery of neurological function in PSS rats,and its mechanism of action may be related to the inhibition of ferroptosis of cortical cells by electroacupuncture regulating the SLC7A11 and GPX4 expression.