Experimental Study On The Effect Of TLR4/MyD88/NF-κB Pathway On The Improvement Of Inflammatory Response In Ischemic Stroke By Using Ultrasound-assisted Drug-drug Electrotherap

Objective:To investigate the effects of TCM ultrasound drug permeation electrotherapy on the neurological impairment score,the percentage of cerebral infarct volume,the histopathological morphology of the ischemic side of the brain,the inflammatory response and the protein expression related to TLR4/MyD88/NF-κB signaling pathway in rats with cerebral ischemia,and to explore the mechanism of the effect of TCM ultrasound drug permeation electrotherapy on cerebral ischemia through the regulation of TLR4/MyD88/NF-κB signaling pathway-mediated inflammation in rats with cerebral ischemia.Methods:A randomized grouping method was used to divide 72 SD rats into 12 sham-operated rats and 60 rats in the modeling group,and middle cerebral artery occlusion(MCAO)model was prepared using the wire embolization method in the modeling group.The rats successfully molded were stratified and randomly divided into model group,Chinese medicine tablet group,blank tablet+TCM ultrasound drug permeation electrotherapy group(hereinafter referred to as "blank tablet+electrotherapy group"),Chinese medicine tablet+TCM ultrasound drug permeation electrotherapy group(hereinafter referred to as "Chinese medicine tablet+electrotherapy group")and butylphthalide group,12 units in each group.The corresponding treatment was given continuously for 7 days.After 7 days of treatment,neurological deficits were scored using the Longa method,and the percentage of cerebral infarct volume was calculated using TTC staining,and Hematoxylin-eosin staining(HE)to observe the morphology of brain cells in each group.The expression of TLR4/MyD88/NF-κB signaling pathway-related proteins in the brain tissue of each group of rats was measured by immunohistochemistry and western blot(WB).Results:After 7 days of treatment,1.neurological function score:compared with the model group,the neurological function score was reduced in the blank tablet+electrotherapy group,the Chinese medicine tablet+electrotherapy group and the butylphthalide group(P<0.05).2.cerebral infarct volume:Compared with the model group,the percentage of cerebral infarct volume was reduced in the herbal tablet group(P<0.05),and the percentage of cerebral infarct volume was reduced in all other treatment groups of rats(P<0.01).3.HE staining results:neuronal cells in the sham-operated group had clear structure,regular morphology,and uniform staining;brain tissue in the model group showed lysis and necrosis,forming skeleton-like cavities,with a large number of inflammatory cells infiltrating and disorganized structural arrangement;brain tissue in the herbal tablet group showed narrower lysis and necrosis,with fewer skeleton-like cavities and inflammatory cells infiltrating than in the model group;the blank tablet+electrotherapy group,the Chinese medicine tablet+electrotherapy group,and the butylphthalide group were basically comparable,with some of the cells pyknosis,deep dyeing and denaturation,and a smaller number of inflammatory cells were seen,with less regular cell arrangement.4.Serum inflammatory factor levels:compared with the model group,serum TNF-α and IL-1β levels in each treatment group were significantly lower than those in the model group(P<0.01).5.Western blot experiment results:compared with the model group,TLR4,MyD88,NF-κB protein expression was significantly lower in the blank tablet+electrotherapy group,Chinese medicine tablet+electrotherapy group and butylphthalide group rats(P<0.05).Conclusion:1.The TCM ultrasound drug permeation electrotherapy instrument can improve the symptoms of neurological function damage in cerebral ischemic rats,reduce the percentage of cerebral infarct volume,improve the pathological morphological structure of brain tissue on the ischemic side,and reduce the content of serum TNF-α and IL-1β,which has a certain protective effect on the brain tissue of cerebral ischemic rats.2.The TCM ultrasound drug permeation electrotherapy instrument can inhibit TLR4/MyD88/NF-κB signaling pathway,inhibit inflammatory response and reduce the release of serum inflammatory factors TNF-α and IL-1β,thus exerting brain tissue protective effects.