摘要
目的研究自噬在血管性痴呆(VD)发病中的作用及自噬抑制剂对其的影响。方法 180只SD大鼠随机分为假手术组、VD组和自噬抑制剂干预组(自噬抑制剂组),每组又分为术后1、2、4、8、12周亚组。采用四血管阻断法制作VD大鼠模型,自噬抑制剂组大鼠在术前1 h给予渥曼青霉素0.5 mg/kg腹腔注射。用Morris水迷宫试验检测大鼠的学习记忆能力;免疫组化SP法检测大鼠海马CA1区自噬相关蛋白Beclin-1、Cathepsin B的表达,Western-blotting法检测自噬活性微管相关蛋白1轻链3(LC3)Ⅱ与Ⅰ的比值。结果与假手术组比较,VD组和自噬抑制剂组各亚组大鼠的学习、记忆能力明显降低;海马CA1区Beclin-1、Cathepsin B蛋白表达水平及LC3Ⅱ/LC3Ⅰ比值明显升高(P<0.05～0.01),并均以术后第4周为最高。而自噬抑制剂组各亚组大鼠的学习、记忆能力明显好于,海马CA1区Beclin-1、Cathepsin B蛋白表达水平及LC3Ⅱ/LC3Ⅰ比值明显低于VD组(P<0.05～0.01)。结论 VD大鼠的认知功能减退,海马自噬相关蛋白表达及自噬活性明显增高;自噬抑制剂对其有改善及抑制的效果。自噬在VD发病中起了重要的作用。
Objective To reserach the effect of autophagy in the pathogenesis of vascular dementia （VD） and the effects of autophagy inhibitor on it. Methods One hundred and eighty SD rats were randomly divided into sham operation group, vascular dementia model group （VD group ） and autophagy inhibitor intervention group （autophagy inhibitor group）. Each group was divided randomly into 1,2,4,8 and 12 weeks subgroups after operation. VD rat models were established by blocking four vessels. Giving the Wortmannin intraperitoneal （0. 5 mg/kg） injection in rats of autophagy inhibitor group 1 h before operation. Learning and memory abilities were detected by Morris water maze test. Expression of the autophagy-related protein Beclin-1 and Cathepsin B in CA1 of rats hippoeampus were detected by SP immunohistochemical method. The ratio of autophagy microtubule-associated protein light chain 3 （LC3） Ⅱ and Ⅰ was detected by Western blotting. Results Compared with sham operation group, the ability of learning and memory was significantly decreased, the expressing of autophagy-related protein Beclin-1, Cathepsin B and the ratio of LC3 Ⅱ and Ⅰ in hippocampal CA1 region were significantly increased in VD group and autophagy inhibitor group （P 〈 0. 05 -0. 01 ） ;which all reached maximum level at 4 week after operation. The ability of learning and memory was significantly better, the expressing of Beelin-1, Cathepsin B protein and the ratio of LC3 Ⅱ and Ⅰin hippocampal CA1 region in each subgroups of autophagy inhibitor group were significantly lower than those in VD group（P 〈0. 05 -0.01 ）. Conclusions Cognitive function is decreased, and the expressing of autophagy-related protein and autophagic activity of hippoeampus are significantly increased in VD rats. The autophagy inhibitors can improve and restrain its effect. Autophagy plays an important role in the pathogenesis of VD.
出处
《临床神经病学杂志》
CAS
北大核心
2013年第6期424-429,共6页
Journal of Clinical Neurology
基金
河北省高等学校科学技术研究重点项目(ZH20-12046)
关键词
血管性痴呆
自噬
自噬相关蛋白
微管相关蛋白1轻链3
自噬抑制剂
vascular dementia
autophagy
autophagy-related protein
microtubule-associated protein lightchain 3
autophagy inhibitor
