RESUMO
Endometritis, a common inflammation of the uterus, often causes severe damage to human and animal reproductive health. Polydatin is a polyphenol extracted from the rhizome of Polygonum cuspidatum that has anti-inflammatory and anti-oxidative effects. The purpose of this study was to investigate the underlying protective effects and mechanisms of polydatin against lipopolysaccharide (LPS)-induced endometritis in mice. The mouse model of endometritis was established by injection of LPS through the vagina. The uterine tissues of each group were gathered to analyze histopathological changes, inflammatory cytokine production, and the degree of activation of the NF-κB and Nrf2 signaling pathways. The myeloperoxidase (MPO) activity assay indicated that polydatin treatment significantly alleviated inflammatory cell infiltration in LPS-induced endometritis mice. Furthermore, polydatin treatment remarkably impeded the expression of TNF-α, IL-1ß, and IL-6 by ELISA assay. Hematoxylin-eosin staining (H&E) showed that polydatin significantly decreased impairment of the uterus. In addition, polydatin was also found to suppress LPS-induced NF-κB activation in a dose-dependent manner. The expression of Nrf2 and HO-1 was enhanced by polydatin treatment. All the results suggest that polydatin helpfully alleviates LPS-induced endometritis by suppressing the NF-ĸB signaling pathway and activating the Nrf2 signaling pathway.
Assuntos
Endometrite/tratamento farmacológico , Glucosídeos/farmacologia , Lipopolissacarídeos/efeitos adversos , Substâncias Protetoras/farmacologia , Estilbenos/farmacologia , Animais , Anti-Inflamatórios/farmacologia , Citocinas/metabolismo , Modelos Animais de Doenças , Endometrite/induzido quimicamente , Feminino , Heme Oxigenase-1/metabolismo , Interleucina-1beta/metabolismo , Interleucina-6/metabolismo , Proteínas de Membrana/metabolismo , Camundongos , Camundongos Endogâmicos BALB C , Fator 2 Relacionado a NF-E2/metabolismo , NF-kappa B/metabolismo , Peroxidase/metabolismo , Transdução de Sinais/efeitos dos fármacos , Fator de Necrose Tumoral alfa/metabolismo , Útero/efeitos dos fármacos , Útero/patologia , VaginaRESUMO
Endometritis is an inflammatory disease of the uterus caused by bacterial infection, and it affects both human and animal health. This study aims to investigate the protective effects and molecular mechanisms of probiotics such as Clostridium tyrobutyricum (C. tyrobutyricum) on Staphylococcus aureus (S. aureus)-induced endometritis. The results showed that S. aureus infection significantly induced the pathological damage of the uterus, increased the production of pro-inflammatory cytokines, such as TNF-α and IL-1ß, and attenuated the expression of tight junction proteins of uterine tissues. However, C. tyrobutyricum pretreatment obviously reduced the inflammatory response and reversed the changes of tight junction proteins of the uterus induced by S. aureus. Together, the data showed that C. tyrobutyricum also inhibited the expression of the TLR2/NF-κB signaling pathway and HDAC induced by S. aureus. In addition, the treatment of mice with live C. tyrobutyricum, spent culture supernatants (SCS) from C. tyrobutyricum, rather than inactive C. tyrobutyricum, inhibited the inflammatory response induced by S. aureus. Through further research, we found that the levels of butyrate in both blood and uterine tissues of mice treated with C. tyrobutyricum were significantly increased. These findings underscore the protective effect of C. tyrobutyricum on endometritis by enhancing the uterus barrier integrity and inhibiting the inflammatory response. The anti-inflammatory mechanism may occur through the regulation of the expression of TLR2/NF-κB and HDAC, and C. tyrobutyricum can be a potentially therapeutic candidate for the treatment of endometritis.