Based on the NLRP3 inflammasome activity mediated by TLR4/MyD88/NF-κB pathway,to investigate the manipulation mechanism of abdominal massage to improve the hippocampal inflammatory injury in CUMS model rats
Objective To observe the effect of abdominal massage on the activity of NLR protein 3(NLRP3)inflammasome mediated by toll-like receptor 4(TLR4)/myeloid differentiation factor 88(MyD88)/nuclear factor-KB(NF-κB)pathway in hippocampus of rats with depression.To explore the mechanism of abdominal massage to improve the hippocampal inflammatory damage in rats with depression.Methods 40 rats were randomly divided into 4 groups and the depression rat model was reproduced by chronic unpredictability mild stress.Iba1 immunofluorescence staining was used to detect the activation degree of microglia in hippocampal CA region of rats,and ELISA was used to detect the contents of tumor necrosis factor α(TNF-α),interleukin-1β(IL-1β),white hormone 6(IL-6)and interleukin-10(IL-10)in hippocampal tissue of rats.Western blot and real-time quantitative PCR were used to detect the expression of TLR4,MyD88,p-NF-κB,NLRP3 and ASC proteins and their genes in hippocampal tissues of rats in each group.Results(1)Compared with the normal group,the proportion of activated microglia in CA1,CA2,CA3 and CA4 regions of hippocampus in the model group was significantly increased(P＜0.01).Compared with the model group,the proportion of activated microglia in CA1,CA2 and CA4 regions of hippocampal tissue of rats in the abdominal oscillation group and the fluoxetine group were significantly decreased(P＜0.01),the proportion of activated microglia in CA3 region of hippocampal tissue in the fluoxetine group was significantly lower than that in the model group(P＜0.05),compared with the model group,the proportion of activated microglia in CA3 region of hippocampal tissue of rats in the shaking group had a decreasing trend.(2)Compared with the normal group,the contents of TNF-α,IL-1β,IL-6 and Caspase-1 in hippocampus of rats in the model group were significantly increased(P＜0.01),IL-10 content was significantly decreased(P＜0.01).Compared with the model group,the IL-10 content of rats in the abdominal oscillation group and the fluoxetine group was significantly increased(P＜0.01),the contents of TNF-α,IL-1β,IL-6 and Caspase-1 were significantly decreased(P＜0.01).(3)Compared with the normal group,the protein and mRNA contents of TLR4,MyD88,p-NF-κB,NLRP3 and ASC in hippocampus of the model group were significantly increased(P＜0.01).Compared with the model group,the protein contents of TLR4,MyD88,p-NF-κB and NLRP3 in hippocampus of the fluoxetine group were significantly decreased(P＜0.01),the protein content of ASC decreased significantly(P＜0.05);the mRNA contents of TLR4,MyD88,p-NF-κB,NLRP3 and ASC in the fluoxetine group were significantly decreased(P＜0.01).Compared with the model group,the protein content of TLR4 and ASC in hippocampal tissue of rats in the abdominal oscillation group were decreased significantly(P＜0.05),the protein contents of MyD88,p-NF-κB and NLRP3 were significantly decreased(P＜0.01);the mRNA contents of TLR4,MyD88,NF-κB and NLRP3 were significantly decreased(P＜0.01),mRNA content of ASC were decreased significantly(P＜0.05).Conclusion The mechanism of abdominal massage to relieve depression-like behavior in the depressed model rats is related to inhibition of NLRP3 in-flammasome activity mediated by TLR4/MyD88/NF-κB pathway in hippocampus and improvement of in-flammatory injury in hippocampus.
abdominal massagedepressionthe sea horseinflammatory injuryToll-like receptor 4/myeloid differentiation factor 88/nuclear factor-κB pathwayNLR protein 3 inflammasomeactivation of microglia
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