膈下逐瘀汤加减方通过ROS/P38MAPK信号通路改善输卵管炎性不孕的机制研究OA

Objective To investigate the therapeutic mechanism of Jiajian Gexia Zhuyu Decoction(膈下逐瘀汤加减方,JGZD)in ameliorating salpingitis inflammatory infertility(SOI)with qi stagnation and blood stasis syndrome via the reactive oxygen species(ROS)/p38 mitogen-activated protein Kinase(P38MAPK)pathway.Methods Eighty female Sprague-Dawley rats were randomly assigned to four groups:blank control,model(SOI),JGZD,and positive control(levofloxacin).The JGZD group was administered the decoction at 2.16 g·kg-1·d-1,and the positive control group received levofloxacin at 0.045 g·kg-1·d-1 via intragastric gavage for 28 con-secutive days.Upon completion,fallopian tube morphology was examined.The TCM syndrome score for qi stagnation and blood stasis was evaluated.Pathological changes were observed via hematoxylin-eosin(HE)staining.Protein expression of Bax,Bcl-2,Caspase-3,Cleaved Caspase-3,p38 MAPK,and p-p38 MAPK in fallopian tubes was detected by Western blot(WB).Apoptosis was assessed by terminal deoxynucleotidyl transferase dUTP nick end labeling(TUNEL)staining.Serum levels of IL-1β,IL-10,and ROS,as well as fallopian tube levels of superoxide dismutase(SOD)and malondialdehyde(MDA),were measured by enzyme-linked immunosorbent assay(ELISA).mRNA expression of Bax,Bcl-2,Caspase-3,and p38 MAPK was quantified by reverse transcription quantitative poly-merase chain reaction(RT-qPCR).Pregnancy rates were recorded.Results The model group exhibited uneven luminal dilation and wall thickening in fallopian tubes,along with a significantly increased TCM syndrome score.The JGZD group showed markedly improved tubal pathology,a significantly reduced syndrome score,and an increased pregnancy rate.Compared with the blank control,the model group demonstrated significantly elevated levels of apoptosis,oxidative stress markers(ROS,MDA;decreased SOD),and inflammatory cytokines(IL-1β;decreased IL-10)in fallopian tubes(P<0.01).These aberrant increases were significantly reversed by JGZD treatment(P<0.01,P<0.05).Conclusion JGZD ameliorated tubal morphology and function in rats with SOI and qi stagnation and blood stasis syndrome.Its mechanisms involve alleviating inflammation and oxidative damage,and inhibiting fallopian tube cell apoptosis via modulation of the ROS/P38MAPK signaling pathway,thereby delaying disease progression and improving fertility.