Abstract: Objective To explore the role of P2RX7 and histone modification in trichostatin A (TSA) inhibiting NLRP3 and alleviating ovarian damage caused by cigarette smoke (CS) exposure in mice. Methods An mouse ovarian injury model was prepared by CS exposure twice daily for 30 days. TSA was injected intraperitoneally into CS-exposed mice on alternate days in the TSA-treated group. HE staining was used to observe the morphological changes of ovary after CS exposure. HDAC1, HDAC2, NLRP3, P2RX7 and EZH2 levels in ovary were detected by Western blot assay. Global modification levels of H3K4me1, H3K4me2, H3K9ac and H3K27me3 were also assessed by Western blot assay. Results Compared with the control group, the total ovary volume and the total number of follicles were reduced in the CS group, and the ovarian cortex was atrophy. TSA can effectively inhibit the morphological and structural changes of the mouse ovarian tissue caused by CS exposure. The expression levels of HDAC1, HDAC2, NLRP3 and P2RX7 in ovarian were significantly higher in the CS group than those in the control group. TSA effectively restored the decreased ovarian volume, cortex atrophy and follicle reduction induced by CS exposure (P＜0.05). Western blot results showed that TSA significantly inhibited the increased expression levels of NLRP3 and P2RX7 induced by CS exposure. Furthermore, TSA significantly inhibited expression levels of global H3K4me1, H3K4me2 and H3K9ac modifications induced by CS exposure (P＜0.05). Conclusion P2RX7 and histone modifications participate in the activation of NLRP3 inflammasome and the alleviation of TSA injury induced by CS exposure in model mice.

Key words: environmental exposure, tobacco smoke pollution, NLR family, pyrin domain-containing 3 protein, pyroptosis, histone code, ovary, Trichostatin A