Ameliorative Effect of Hemiplegic Oral Solution on Ischemic Stroke Rats Based on TLR4/NLRP3 Signaling Pathway
Objective To study the improvement effect and mechanism of hemiplegic oral solution on ischemic stroke model rats.Methods Totally 40 rats were randomly divided into sham operation group,model group,ginkgo leaf tablet group(positive control,5.76 mg/kg),low-dose group and high-dose group of hemiplegic oral solution(1.5,6.0 g/kg).The rat model of middle cerebral artery occlusion(MCAO)was duplicated with the improved suture method in other groups except the sham operation group.Rats in each group continuous administered for 5 days after modeling.During experiment,general condition of the rats and the neurological function score was examined and performed respectively.Organ index was calculated after the last administration.ELISA was applied to measure the levels of interleukin-1β(IL-1β),interleukin-6(IL-6),tumor necrosis factor-α(TNF-α),and kit method evaluate malondialdehyde(MDA),superoxide dismutase(SOD),glutathione(GSH)in brain tissue.HE staining was used to observe the histopathological changes in the ischemic area.Western blotting was employed to assay the expression levels of apoptosis-related and TLR4/NLRP3 signaling pathway-related proteins in the rat brain tissue.Results Compared with the sham operation group,neurological deficit score,brain tissue index,spleen tissue index,IL-1β,IL-6,TNF-α and MDA levels were significantly increased(P<0.01),and SOD,GSH levels were significantly lowered in the brain tissue of model group(P<0.01).The brain tissue showed structural relaxation,a large number of irregular arrangement of cavities,nuclear shrinkage and other typical lesions.Compared with model group,high-dose hemiplegic oral solution group and ginkgo leaf tablet group decreased the neurological deficit score,lowered the IL-1β,IL-6,TNF-α and MDA levels(P<0.05),and elevated the SOD and GSH levels in the brain tissue(P<0.01),the pathology of brain tissue was improved obviously.Compared with the sham operation group,the model group showed elevated protein levels of Bax,TLR4,p-NF-κB,NF-κB,NLRP3(P<0.01),and inhibited protein level of Bcl-2 in the brain tissue(P<0.01).Compared with the model group,the low and high dose groups of hemiplegia oral solution could effectively reverse the protein expression trend of the above-mentioned brain tissue injury.Conclusion Hemiplegia oral solution has powerful therapeutic effect on ischemic stroke model rats,the mechanism may be related to the regulation of TLR4/NLRP3 signaling pathway to inhibit neuroinflammatory response and oxidative stress.
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