脑卒中前敲减HDAC2改善光照脑缺血模型小鼠的行为学缺陷

发布时间：2018-05-29 06:36

本文选题：组蛋白去乙酰化酶 + 脑卒中　；参考：《南京医科大学学报(自然科学版)》2017年09期

【摘要】：目的:探讨脑卒中前蛋白去乙酰化酶2(histone deacetylase 2,HDAC2)对于光诱导血栓形成性脑缺血模型小鼠行为学缺陷的作用。方法:通过微量给药系统将腺相关病毒AAV-CAG-EGFP-Cre(2μL)注射至HDAC2flox/flox鼠的运动皮层用以敲减HDAC2,通过免疫荧光以及免疫印迹(Western blot)分析确证病毒AAV-CAG-EGFP-Cre与对照病毒AAV-CAG-EGFP的表达。7 d后进行光诱导血栓形成性脑缺血造模,并于造模前第3天以及造模后第8天采用网格实验和圆筒实验分别检测造模前后AAV-CAG-EGFP-Cre组与AAV-CAG-EGFP组行为学的改变。结果:病毒AAV-CAG-EGFP-Cre相较于对照AAV-CAG-EGFP能特异性地敲减HDAC2,免疫荧光表现为GFP与HDAC2双阳性细胞数减少,Western blot显示针孔周围区HDAC2表达水平降低(P0.05)。脑缺血前后的行为学检测表明病毒干预后,HDAC2的下调对缺血前行为学无影响,但显著降低了脑缺血后网格实验的失足率(P0.001)与圆筒实验的不对称指数(P0.001),促进了行为学改善。结论:脑卒中前通过重组病毒敲减HDAC2,可以改善脑卒中后小鼠行为学缺陷。
[Abstract]:Aim: to investigate the effect of 2(histone deacetylase _ 2 (HDAC _ 2) on behavioral deficiency in mice with light induced thrombotic cerebral ischemia. Methods: Adenovirus-associated virus (AAV-CAG-EGFP-Cre(2 渭 L) was injected into the motor cortex of HDAC2flox/flox mice to knock down HDAC2.The expression of AAV-CAG-EGFP-Cre and control virus AAV-CAG-EGFP was confirmed by immunofluorescence and Western blotanalysis. Making models of thrombotic cerebral ischemia, The behavior changes of AAV-CAG-EGFP-Cre group and AAV-CAG-EGFP group before and after modeling were detected by grid experiment and cylinder experiment on the 3rd and 8th day before and after modeling respectively. Results: compared with control AAV-CAG-EGFP, AAV-CAG-EGFP-Cre could specifically knock down HDAC2. The immunofluorescence showed that the number of double positive cells of GFP and HDAC2 decreased. Western blot showed that the expression of HDAC2 in the area around the pinhole was lower than that in the control group (P 0.05). The behavioral tests before and after cerebral ischemia showed that the down-regulation of HDAC2 had no effect on preischemic behavior, but significantly decreased the slip rate (P0.001) of grid test after cerebral ischemia and the asymmetry index (P0.001) of cylinder experiment, which promoted the improvement of behavior. Conclusion: the reduction of HDAC 2 by recombinant virus before stroke can improve the behavioral defect of mice after stroke.
【作者单位】：南京医科大学药学院药理实验室;
【基金】：国家自然科学基金重点项目(31530091) 科技部973计划(2011CB504404)
【分类号】：R-332;R743.3

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