Effect Of Taohong Siwu Decoction On Pyroptosis In Rats With Cerebral Ischemia Reperfusion

Objective:Taohong Siwu Decoction(THSWD)is one of the classic prescriptions for promoting blood circulation and removing blood stasis,which has a good therapeutic effect on ischemic stroke.In order to provide experimental and theoretical basis for further comprehensive development and utilization of THSWD,the effects of THSWD on pyroptosis in rats with middle cerebral artery occlusion with reperfusion(MCAO/R).Method:MCAO/R model of SD rats were established by the suture-occluded method.After24 hours of surgery,MCAO/R rats were randomly divided into 5 groups based on Longa behavioral scores,which were model group,nimodipine group,THSWD high,medium and low dose group(18,9,and 4.5 g/kg,respectively),rats of sham group without thread embolus.All rats were treated by intragastric administration for 7 days.After 2 hours of the last intragastric administration,all rats were subjected for behavioral function with Bederson scores.And the rats were quickly decapitated and the serum and brain tissue were separated for use.TTC staining method was used to detect the volume of cerebral infarction in rats,the pathological damage of brain tissue was observed by HE staining,enzyme-linked immunosorbent assay was used to detect the levels of inflammatory factors in penumbra and serum.NLRP3 and Caspase-1 were detected by immunofluorescence.Western blot was used to detect NLRP3,Caspase-1,ASC,TXNIP,and GSDMD in penumbra.HMGB1/RAGE,TLR4/NF-?B,and MAPK protein were also detected by western blot.Results:Compared with model group,the THSWD and nimodipine groups improved the behavioral function,cerebral infarction volume was significantly reduced,pathological damage was improved in penumbra.These results of pyroptosis levels in penumbrashowed that the levels of IL-1? and IL-18 in the THSWD and nimodipine treatment groups were significantly reduced.THSWD could significantly reduce the expression levels of NLRP3,Caspase-1,Caspase-1 p10,ASC,TXNIP,GSDMD.Similarly,THSWD could significantly reduce the expression levels of HMGB1/RAGE,TLR4/NF-?B,p38 MAPK,and JNK in penumbra.Conclusion:These results showed that THSWD could reduce the level of inflammatory response,inhibites the activation of NLRP3 inflammatory bodies,down-regulate GSDMD in MCAO/R rats.THSWD could inhibit pyroptosis,which may be affected by inhibiting HMGB1/TLR4/NF-?B,MAPK signaling pathways.