金丝桃苷调节TXNIP/NLRP3信号通路对细菌性脑膜炎大鼠神经炎症的影响OACSTPCD

Objective:To analyze the effects of Hypericin(Hyp)on neuroinflammation in bacterial meningitis(BM)rats by regulating the thioredoxin-interacting protein(TXNIP)/nucleotide-binding oligome-rization domain-like receptor protein 3(NLRP3)signaling pathway.Methods:Fifteen healthy rats were ran-domly selected as the control group(tail vein injection of saline).BM model rats were randomly divided into BM group(tail vein injection of saline),L-Hyp group(tail vein injection of 10mg/kg Hyp),H-Hyp group(tail vein injection of 50mg/kg Hyp),TXNIP-AAV group(tail vein injection of TXNIP-AAV),AAV group(tail vein injection of AAV-NC),and Resveratrol(Res)group(tail vein injection of 30mg/kg Res).Neuro-logical function after treatment was evaluated using the Loeffler score;white blood cell(WBC)count was de-termined using a blood cell analyzer;reactive oxygen species(ROS),interleukin(IL)-1β,IL-6,and tumor necrosis factor-alpha(TNF-α)levels in cerebrospinal fluid(CSF)were analyzed by ELISA;brain tis-sue water content was measured;pathological changes in brain tissue were observed using HE staining;cell apoptosis in brain tissue was observed using TUNEL staining;and protein expressions of TXNIP,NLRP3,caspase-1,apoptosis-associated speck-like protein(ASC),ionized calcium-binding adaptor molecule 1(Iba1),and IL-1β in brain tissue were analyzed using Western blotting.Results:Compared with the control group,the BM group showed increased levels of ROS,WBC,IL-1β,IL-6,and TNF-α in CSF,increased brain tissue water content and cell apoptosis rate,and decreased Loeffler scores(P＜0.05).Compared with the BM group,the L-Hyp and H-Hyp groups showed increased Loeffler scores,and decreased levels of ROS,WBC,IL-1β,IL-6,and TNF-α in CSF,brain tissue water content,and cell apoptosis rate(P＜0.05).Compared with the H-Hyp group,the TXNIP-AAV and AAV groups showed increased levels of ROS,WBC,IL-1β,IL-6,and TNF-α in CSF,brain tissue water content,and cell apoptosis rate,and decreased Loeffler scores(P＜0.05),whereas the Res group showed increased Loeffler scores and decreased levels of ROS,WBC,IL-1β,IL-6,and TNF-α in CSF,brain tissue water content,and cell apoptosis rate(P＜0.05).The brain tissues of rats in the control group showed normal morphology;in the BM,TXNIP-AAV,and AAV groups,brain tissues showed morphological changes,disordered cell arrangement,and nuclear shrinkage;in the L-Hyp,H-Hyp,and Res groups,brain tissues showed improved morphology,with reduced cell necrosis and shrinkage.Compared with the control group,the BM group showed increased expressions of TXNIP,NL-RP3,caspase-1,ASC,Iba1,and IL-1β in brain tissues(P＜0.05).Compared with the BM group,the L-Hyp and H-Hyp groups showed decreased expressions of TXNIP,NLRP3,caspase-1,ASC,Iba1,and IL-1β in brain tissues(P＜0.05).Compared with the H-Hyp group,the TXNIP-AAV and AAV groups showed increased expressions of TXNIP,NLRP3,caspase-1,ASC,Iba1,and IL-1β in brain tissues,while the Res group showed decreased expressions of these proteins(P＜0.05).Conclusion:Hypericin may inhibit neuroin-flammation in BM rats,possibly through inhibition of the TXNIP/NLRP3 pathway.