| HDAC3参与调节NFIL3与小鼠内脏高敏感作用的研究 |
| 投稿时间：2025-02-23 修订日期：2025-03-24 点此下载全文 |
| 引用本文：王雪雪,喻雪,姜子凤,费素娟.HDAC3参与调节NFIL3与小鼠内脏高敏感作用的研究[J].医学研究杂志,2025,54(8):134-140, 159 |
| DOI：
10.11969/j.issn.1673-548X.2025.08.022 |
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| 中文摘要:目的 探究组蛋白去乙酰基酶3(histone deacetylase 3,HDAC3)在肠道节律基因白细胞介素3调控的核因子(nuclear factor, interleukin 3 regulated,NFIL3)与小鼠内脏高敏感之间的作用。方法 将C57BL/6J小鼠随机分为对照组(contrl group,CON组)、睡眠剥夺组(sleep deprivation group,SD组)和HDAC3抑制剂干预组(SD+RGFP966组)。通过旷场实验及高架迷宫试验来检测小鼠的行为,结直肠扩张实验和痛阈来评估内脏敏感度的高低；应用苏木精-伊红染色评估各组结肠组织的病理学变化,酶联免疫吸附试验(enzyme-linked immunosorbent assay,ELISA)法检测血清中炎性细胞因子(IL-17、IL-6)及抗炎性细胞因子(IL-10)的表达,实时荧光定量聚合酶链反应(real-time fluorescence quantitative polymerase chain reaction,RT-qPCR)法测定结肠组织中连接蛋白(ZO-1、Occludin)、炎性细胞因子(IL-1β、IL-6)的mRNA表达,Western blot法检测结肠组织中NFIL3、HDAC3及炎性细胞因子(TNF-α、IL-1β)和连接蛋白(ZO-1、Occludin)的蛋白表达。结果 与CON组比较,SD组小鼠具有焦虑抑郁样行为且内脏敏感度增加(P＜0.05)。苏木精-伊红染色结果显示,结肠组织结构未见明显破坏。Western blot法及RT-qPCR法检测结果显示,结肠组织中炎性细胞因子的表达增加(P＜0.05),而连接蛋白表达减少(P＜0.05)。Western blot法检测结果显示,HDAC3及NFIL3蛋白表达均增高；与SD组比较,SD+RGFP966组小鼠焦虑抑郁样行为及内脏敏感度均得到改善(P＜0.05),炎性细胞因子的表达降低(P＜0.05),而连接蛋白表达增加(P＜0.05)；HDAC3被抑制后,NFIL3的表达亦降低(P＜0.05)。结论HDAC3抑制剂RGFP966可以通过调节肠道节律基因NFIL3来改善小鼠的内脏高敏感度。 |
| 中文关键词:肠易激综合征 睡眠剥夺 NFIL3 HDAC3 内脏高敏感 RGFP966 |
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| Abstract:Objective To explore the role of histone deacetylase 3 (HDAC3) and the intestinal rhythm gene nuclear factor, interleukin 3 regulated (NFIL3) and visceral hypersensitivity in mice. Methods C57BL/6J mice were randomly divided into normal group (control group, CON group), sleep deprivation group (SD group), and HDAC3 inhibitor intervention group (SD + RGFP966group). The behaviors of mice were detected by open field test and elevated plus maze test, and visceral sensitivity was evaluated by colonic dilation test and pain threshold. The pathological changes of colon tissues in each group were evaluated by hematoxylin-eosin staining, and the expressions of inflammatory factors (IL-17, IL-6) and anti-inflammatory factors (IL-10) in serum were detected by enzyme-linked immunosorbent assay (ELISA). The mRNA expressions of junction proteins (ZO-1, Occludin), inflammatory factors (IL-1β, IL-6) in colon tissues were determined by real-time fluorescence quantitative polymerase chain reaction (RT-qPCR). The protein expressions of NFIL3, HDAC3 and inflammatory factors (TNF-α, IL-1β) in colon tissues were detected by Western blotting. ResultsCompared with the CON group, mice in the SD group exhibited anxiety and depression-like behaviors and increased visceral sensitivity (P<0.05). The hematoxylin-eosin results showed no obvious damage to the structure of colon tissues. The results of Western blot and RT-qPCR showed that the expressions of inflammatory factors in colonic tissue increased (P<0.05), while the expressions of junction proteins decreased (P<0.05). The results of Western blot showed that the protein expressions of HDAC3 and NFIL3 increased. Compared with the SD group, the anxiety and depression-like behaviors and visceral sensitivity of mice in the SD+RGFP966group were improved (P<0.05), and the expressions of inflammatory factors decreased (P<0.05), while the expressions of junction proteins increased (P<0.05). The expression of NFIL3decreased after HDAC3 inhibition (P<0.05). Conclusion HDAC3 inhibitor RGFP966 can improve the visceral hypersensitivity of mice by regulating the intestinal rhythm gene NFIL3. |
| keywords:Irritable bowel syndrome Sleep deprivation NFIL3 HDAC3 Visceral hypersensitivity RGFP966 |
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