Exploring the Efficacy and Mechanism of Modified Yinjia Formula in the Treat-ment of Persistent Genital Tract Chlamydia Infection Based on Ras/Raf/MEK/ERK Signaling Pathway
Objective:To investigate the efficacy and mechanism of modified Yinjia formula in the treatment of persistent genital tract chlamydia trachomatis infections based on the targeted regulation of CD8+T cell autophagy pathway.Methods:Thirty-six BALB/c mice,except for the blank group,were inoculated intravaginally with chlamydia to establish a model of persistent chlamydia trachomatis infection.After successful modeling,patients were divided into groups and given low,medium and high doses of Yinjia modifiedformula and azithromycin by continuous gavage for 4 weeks,respectively.HE staining was used to observe the histomorphologic changes of uterus and fallopian tube tissues of the mice.Real-time fluorescence quantitative polymerase chain reaction was used to detect the expression level of chlamydia trachomatis genes in the low reproductive tract.Proportion of OX40 and LAG-3 positive cells in mouse lymph nodes was detected by flow cytometry.Immunoblotting was used to detect the expression of autophagy-related protein Beclin-1,Atg5,LC3Ⅱ/LC3Ⅰ,p62,and Ras/Raf/MEK/ERK pathway protein in mouse splenic CD8+T cells.Results:Compared with the model group,the inflammatory cell infiltration was reduced to different degrees in all treatment groups.Among them,only a very small amount of in-flammatory cell infiltration was observed in the uterus and fallopian tubes in the high-dose group of traditional Chi-nese medicine,and no significant inflammatory exudation and thickening was observed in the fallopian tubes.Compared with the model group,the expression of Beclin-1,Atg5,LC3Ⅱ/LC3Ⅰ was decreased in all treatment groups(P＜0.01),while the protein expression of p62,Ras,P-Raf,P-MEK and P-ERK was up-regulated(P＜0.01).Additionally,the proportion of OX40 and LAG-3 positive cells in lymphocytes was decreased(P＜0.01).A-mong them,Beclin-1,Atg5,LC3Ⅱ/LC3Ⅰ protein expression as well as the percentage of OX40 and LAG-3 positive cells were the lowest in the high-dose group of traditional Chinese medicine(P＜0.01).Conclusions:The modi-fied Yinjia formula may inhibit the autophagic activity of CD8+T cells through the Ras/Raf/MEK/ERK signaling pathway,thereby enhancing the targeted clearance function of chlamydia trachomatis inclusion bodies by CD8+T cells and delaying the process of persistent chlamydia trachomatis infection in the reproductive tract.
万方数据
维普
