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Abstract: Objective To investigate the molecular mechanisms of HDAC3 inhibitor RGFP966 in alleviating endometrial fibrosis. Methods A total of 18 female SD rats (6-8 weeks) were randomly divided into 3 groups: Control group, IUA Model group (intrauterine adhesion rat Model), and RGFP966 Treatment group ( IUA model group rats were treated with HDAC3 inhibitor RGFP966), with 6 rats in each group. IUA rat model was established. ELISA was used to determine the levels of the serum inflammatory cytokines TNF-α, IL-1β and IL-6. qPCR was used to determine the relative mRNA expression levels of EMT markers E-cadherin, N-cadherin, α-SMA and Vimentin. Western blotting was used to determine the protein expression levels of TGF-β1, SMAD3, phosphorylated STAT-1, STAT-1, AIM2, IL-18, cleaved IL-1β and IL-1β. Results The walls of uterine horn in the IUAModel group were thinner, the levels of serum inflammatory cytokines TNF-α, IL-1β and IL-6 were increased when compared with those in the Control group (P<0. 05). The relative expression levels of Ecadherin mRNA were decreased, while the relative expression levels of N-cadherin, α-SMA and Vimentin mRNA were increased (P < 0. 05). The expression levels of TGF-β1, SMAD3, p-STAT-1 were enhanced (P < 0. 05). And the expression levels of AIM2, IL-18, cleaved IL-1β were increased (P <0. 05). The above indicators were partially reversed in RGFP966 Treatment group when compared withthose in the IUA Model group (P<0. 05). No significant differences in the expression levels of STAT-1and IL-1β were seen among the three groups (P >0. 05). Conclusion HDAC3 inhibitor RGFP966 canalleviate endometrial fibrosis by down-regulating TGF-β1/ SMAD3/ STAT-1 signaling pathway to inhibitAIM2 inflammasome activation and EMT.

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