Histological Features of Uterine Myometrial Dysfunction:Possible Involvement of Localized Inflammation  

作　　者：Sheng-lan ZHU Hui-ting ZHANG Yuan-yuan DU Yi JIANG Shao-shuai WANG Wen-cheng DING Ling FENG 

机构地区：[1]National Clinical Research Center for Obstetrics and Gynecology,Tongji Hospital,Tongji Medical College,Huazhong University of Science and Technology,Wuhan,430030,China [2]Department of Obstetrics and Gynecology,Tongji Hospital,Tongji Medical College,Huazhong University of Science and Technology,Wuhan,430030,China

出　　处：《Current Medical Science》2024年第3期633-641,共9页当代医学科学（英文）

基　　金：supported by the National Key Research and Development Program of China(No.2021YFC2701500).

摘　　要：Objective The latest perspective suggests that elevated levels of inflammation and cytokines are implicated in atonic postpartum hemorrhage.Lipopolysaccharide(LPS)has been widely used to induce inflammation in animal models.Therefore,this study aimed to induce uterine inflammation using LPS to investigate whether local inflammation triggers dysfunction and atrophy in the myometrium,as well as the potential underlying molecular mechanisms involved.Methods In vivo,an animal model was established by intraperitoneal injection of 300μg/kg LPS in rats on gestational day 21.Hematoxylin-eosin(H&E)staining and Masson staining were employed to determine morphological changes in the rat uterine smooth muscle.Enzyme-linked immunosorbent assay(ELISA)was used to detect inflammatory cytokines.Immunohistochemistry,tissue fluorescence,and Western blotting were conducted to assess the expression levels of the uterine contraction-related proteins Toll-like receptor 4(TLR4)and the nuclear factor kappa-B(NF-κB)signaling pathway.In vitro,human uterine smooth muscle cells(HUtSMCs)were exposed to 2μg/mL LPS to further elucidate the involvement of the TLR4/NF-κB signaling pathway in LPS-mediated inflammation.Results In this study,LPS induced uterine myometrial dysfunction in rats,leading to a disorganized arrangement,a significant increase in collagen fiber deposition,and widespread infiltration of inflammatory cells.In both in vivo animal models and in vitro HUtSMCs,LPS elevated IL-6,IL-1β,and TNF-αlevels while concurrently suppressing the expression of connexin 43(Cx43)and oxytocin receptor(OXTR).Mechanistically,the LPS-treated group exhibited TLR4 activation,and the phosphorylation levels of p65 and IκBαwere notably increased.Conclusion LPS triggered the TLR4/NF-κB signaling pathway,inducing an inflammatory response in the myometrium and leading to uterine myometrial dysfunction and uterine atony.

关 键 词：LIPOPOLYSACCHARIDE inflammatory response TLR4 NF-κB MYOMETRIUM 

分 类 号：R711[医药卫生—妇产科学]