大黄煎剂保留灌肠改善肝性脑病大鼠神经炎症的作用机制研究OACHSSCD

Objective:To observe the effects of Dahuang Decoction Retention Enema on cerebellar neuroinflammation in rats with hepatic encephalopathy(HE),based on the tumor necrosis factor receptor 1(TNFR1)/glutaminase(GLS)/γ-aminobutyric acid transporter 3(GAT3)signaling pathway.Methods:Rats were randomly divided into a blank group,a model group,a lactulose group,and low-,medium-,and high-dose Dahuang Decoction groups according to a random number table.Except for the blank group,all other groups were intraperitoneally injected with thioacetamide(TAA)to establish the HE model.After modeling,contin-uous enema administration was performed for 4 consecutive days,once daily.HE grading and behavioral changes were compared.Pathological changes in liver and cerebellar tissues were observed.Blood ammonia levels and liver function indices were measured.Inflammatory mediators in cerebellar tissue[tumor necrosis factor-α(TNF-α),interleukin-6(IL-6),and interleukin-1 β(IL-1 β)]and the mRNA and protein expression levels of the TNFR1/GLS/GAT3 signaling pathway were detected.Results:There was no statistically significant difference in HE grading among groups after modeling.Compared with the model group,rats in the lactulose group and the medium-and high-dose Dahuang Decoction groups showed increased crossing times on the platform and longer resi-dence time on the rotarod,and the total locomotor distance was increased in all treatment groups.After treatment,pathological chan-ges in liver and cerebellar tissues were alleviated in each group.Blood ammonia levels were reduced in the lactulose group and in the medium-and high-dose Dahuang Decoction groups.Liver function indices were improved in all treatment groups.The mRNA ex-pression levels of TNF-α,IL-6,and IL-1 β in cerebellar tissue were decreased.The mRNA and protein expression levels of TNFR1 and GLS were also reduced.Except for the low-dose Dahuang Decoction group,the mRNA and protein expression levels of GAT3 were decreased in the other groups.Conclusion:Dahuang Decoction Retention Enema reduces blood ammonia levels,improves liver function,alleviates cerebellar inflammatory response,and improves motor coordination in HE rats.The mechanism may be related to inhibition of activation of the TNFR1/GLS/GAT3 signaling pathway.