摘要
目的探讨选择性组蛋白去乙酰化酶6（HDAC6）抑制剂TubastatinA在小鼠脑梗死中的保护作用及其可能的机制。方法第1部分：采用健康成年雄性C57BL／6小鼠，随机分为假手术组和脑梗死组，其中梗死组再分为梗死后1、3、5天3个亚组，应用Westernblotting方法检测各组小鼠梗死灶周围HDAC6表达变化。第2部分：将健康成年雄性C57BL／6小鼠随机分为假手术组、脑梗死组、溶剂对照组及TubastatinA组，采用光化学法建立脑梗死模型，于造模后1、3、5天采用mNSS评分对各组小鼠进行行为学测试，并在造模后3天采用westernblot-ting检测各组小鼠梗死灶周围核因子-κB（NF-κB）、肿瘤坏死因子-α（TNF-α）、白细胞介素-6（IL-6）表达变化。结果与假手术组比较，脑梗死组梗死灶周围HDAC6表达升高，其中梗死后第3天HDAC6表达升高最明显（P〈0．05）。与脑梗死组比较，TubastatinA组神经功能评分下降，Westernblotting检测梗死周围NF-κB、TNF-α、IL-6蛋白表达下降，差异有统计学意义（P〈0．05），溶剂对照组较脑梗死组无显著差异（P〉0．05）。结论选择性HDAC6抑制剂TubastatinA在小鼠脑梗死中可能通过减少NF-κB、TNF-α、IL-6的表达减轻炎症反应，从而发挥神经保护作用。
Objective To investigate the protective effects of tubastatin A, a selective inhibitor of histone deacety- lase 6 （HDAC6） on mice with cerebral infarction and possible mechanisms.Methods Adult male C57BL/6 mice were randomly divided into a sham - operated group and a cerebral infarction group which was then sub - divided into three groups according to their survival 1, 3 and 5 days after infarction.The level of HDAC 6 in the surrounding area of each group＇s infarction foci was detected by Western blotting. Heahhy adult male C57BL/6 mice were randomly divided into a sham - operated group, a cerebral infarction group, a solvent group and a tubastatin A group. A mouse model of cerebral infarction was established using the photochemical method. Behavioral tests were performed 1 d, 3 d and 5 d after model- ing to assess the scores of mNSS in each group. The amounts of nuclear factor - κB （ NF - KB）, tumor necrosis factor - α （TNF-α） and interleukin - 6 （IL- 6） in the surrounding area of each group＇s infarction foci was detected by West, ern blotting. Results Compared to the sham - operated group, the cerebral infarction group produced increased levels of HDAC6 in the surrounding areas of infarction foci, which reached peak on Day 3 after infarction （P 〈 0.05）. Compared with the cerebral infarction group, the mNSS score was reduced for the tubastatin A group, in addition to remarkably de- creased scores of NF - κB, TNF - α and IL - 6 （ P 〈 O. 05 ）. No difference was found between the cerebral infarction group and the solvent group （P 〉 0.05）. Conclusion HDAC 6 can produce neuroprotective effects on mice with cere- bral infarction, possibly through inhibition of the levels of NF -κB, TNF - α and IL - 6.
出处
《徐州医学院学报》
CAS
2016年第4期249-253,共5页
Acta Academiae Medicinae Xuzhou
基金
国家自然科学基金（81571155）致谢：徐州医学院神经生物研究中心实验室
