天津医药

天津医药 ›› 2021, Vol. 49 ›› Issue (10): 1053-1057.doi: 10.11958/20210617

• 实验研究 • 上一篇    下一篇

P2RX7和组蛋白修饰变化在曲古抑菌素A缓解烟草烟雾暴露所致小鼠卵巢损伤中的作用

苗佳宁，丛艳飞，李芳，娄毅，王莉莉   

  1. 1中国医科大学附属盛京医院实验中心，辽宁省环境与代谢疾病动物模型研究与应用重点实验室（邮编117000）；2中国医科大 学生命科学院医学遗传学教研室
  • 收稿日期:2021-03-16 修回日期:2021-06-15 出版日期:2021-10-15 发布日期:2021-10-15
  • 通讯作者: 王莉莉 E-mail:wll_1977_21@163.com
  • 基金资助:
    ERα-Smyd1-P2rx7调控轴在孕期烟草烟雾暴露加重子代Fhl1-/-小鼠类先天性马蹄内翻足骨骼肌表型中的作用机制研究;孕母雌激素调节FOXO3介导的自噬对Fhl1基因敲除小鼠类先天性马蹄内翻足肌肉表型的修饰作用及机制

The role of P2RX7 and histone modification in trichostatin A alleviating mouse ovary injury induced by cigarette smoke exposure

MIAO Jia-ning, CONG Yan-fei, LI Fang, LOU Yi, WANG Li-li   

  1. 1 Medical Research Center of Shengjing Hospital, China Medical University, Key Laboratory of Research and Application of Animal Models for Environmental and Metabolic Diseases, Benxi 117000, China; 2 Department of Medical Genetics, School of Life Sciences, China Medical University
  • Received:2021-03-16 Revised:2021-06-15 Published:2021-10-15 Online:2021-10-15
  • Contact: Lili WANG E-mail:wll_1977_21@163.com

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摘要： 目的 探索P2RX7和组蛋白修饰变化在曲古抑菌素A（TSA）抑制NLRP3缓解烟草烟雾（CS）暴露所致的 小鼠卵巢损伤过程中的作用。方法 通过CS暴露30 d方法制备小鼠卵巢损伤模型，给予TSA进行治疗；HE染色观 察各组小鼠卵巢组织形态；Western blot技术检测各组小鼠卵巢组织组蛋白去乙酰化酶（HDAC）1、HDAC2、NLR家族 Pyrin域蛋白3（NLRP3）、P2RX7、Zeste同源物增强子2（EZH2）表达以及H3K4me1、H3K4me2、H3K27me3和H3K9ac总 的修饰水平变化。结果 与control组相比，CS组小鼠卵巢总体积减小，卵泡总数减少，卵巢皮质发生萎缩，TSA可有 效抑制CS暴露引起的小鼠卵巢组织形态结构改变。CS组小鼠卵巢组织中HDAC1、HDAC2、NLRP3和P2RX7表达水 平较control 组明显升高，TSA 有效抑制了CS 暴露激活的小鼠卵巢组织HDAC1、HDAC2及焦亡相关蛋白NLRP3和 P2RX7的表达（P＜0.05）。CS暴露后小鼠卵巢组织总H3K4me1、H3K4me2和H3K9ac表达水平明显升高，TSA有效抑 制了CS暴露诱导的小鼠卵巢组织总H3K4me1、H3K4me2和H3K9ac的表达上调（P＜0.05）。结论 P2RX7和组蛋白 修饰变化参与CS暴露所致的卵巢NLRP3炎性小体的激活以及TSA缓解卵巢损伤的过程。

关键词: 环境暴露, 烟草烟污染, NLR家族, 热蛋白结构域包含蛋白3, 细胞焦亡, 组蛋白密码, 卵巢, 曲古抑菌素A

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