小白菊内酯通过调节自噬通路改善血管性痴呆大鼠的认知功能

Parthenolide improves cognitive function of vascular dementia rats by regulating autophagy pathway

目的 探讨小白菊内酯(PTL)对血管性痴呆(VD)大鼠的认知改善作用以及对海马区神经元的自噬通路的影响。方法 将8w龄SD大鼠随机分为假手术组,VD组及小白菊内酯干预组。应用双侧颈总动脉结扎法(BCCAO)建立慢性脑低灌注的VD模型。采用Morris水迷宫法检测各组大鼠的认知功能。苏木精-伊红染色观察各组大鼠海马区神经元形态;透射电镜方法检测各组大鼠海马区神经元内自噬小体的变化;Western blot法检测各组大鼠海马区内微管相关蛋白1轻链3 (LC3)和B细胞淋巴瘤-2相互作用蛋白1 (Beclin1)的表达。结果 小白菊内酯可以改善VD大鼠的认知功能(P<0.01),保护海马区神经元,降低神经元内自噬蛋白LC3和Beclin1的表达(P<0.01),降低神经元内的自噬。结论 PTL通过减轻海马区神经元内的过度自噬反应达到改善VD模型大鼠认知功能的作用。

Objective To investigate the effect of parthenolide on improving the cognition and its effect on autophagy pathway of vascular dementia(VD) rats.Methods Eight-week-old SD rats were randomly divided into sham operation group,VD group and parthenolide intervention group.A VD model with chronic cerebral hypoperfusion was established by bilateral common carotid artery occlusion(BCCAO).The cognitive function of the rats in each group was detected by Morris water maze.HE staining was used to observe the morphology of neurons in the hippocampus of the rats in each group;transmission electron microscopy was used to detect the changes of autophagosomes in the neurons of the hippocampus of the rats in each group;Western blot was used to detect the microtubule-associated protein 1 protein light chain 3 and B-cell lymphoma-2 interacting protein 1 in the hippocampus.Results Parthenolide could improve the cognitive function of rats with vascular dementia VD(P<0.01),protect the neurons in the hippocampus,reduce the expressions of autophagy proteins LC3 and Beclinl in neurons(P<0.01),and reduce the autophagy level in the neurons of hippocampus.Conclusion Parthenolide improve the cognitive function of VD rats by reducing excessive autophagy in hippocampal neurons.