依达拉奉对血管性认知功能损害大鼠IL-1β、TNF-α与VEGF表达的影响

目的:观察依达拉奉对血管性认知功能损害大鼠脑组织和血清VEGF、IL-1β和TNF-α表达的影响,探讨依达拉奉对血管性认知功能损害脑保护作用机制。方法:永久性结扎大鼠双侧颈总动脉法建立血管性认知功能损害血管性认知功能损害动物模型,Wistar大鼠随机分为假手术组(S组)、血管性认知功能损害模型组(M组)、依达拉奉治疗组(MT组)。酶联免疫吸附法检测大鼠脑组织IL-1β、TNF-α表达水平和血清水平,蛋白质免疫印迹法和酶联免疫吸附法检测大鼠脑组织VEGF,水迷宫实验和跳台实验检测行为学改变。结果模型组大鼠有明显的学习、记忆、行为障碍,经过依达拉奉治疗后血管性认知功能损伤大鼠的学习、记忆、行为功能明显改善。MT组IL-1β、TNF-α表达较M组降低(P<0.01),MT组VEGF表达较M组增高(P<0.01);MT组VEGF、IL-1β、TNF-α表达较S组增高(P<0.01);M组VEGF、IL-1β、TNF-α表达较N、S组显著增高(P<0.01)。结论依达拉奉能降低血管性认知功能损害大鼠脑组织和血清IL-1β、TNF-α水平、增强VEGF表达,依达拉奉可以通过抑制血管性认知功能损害炎症反应和增强血管修复发挥脑保护作用。

Minocycline reduces astrocytic reactivation and neuroinflammation in the hippocampus of a vascular cognitive impairment rat model

Objective To study the neuroprotective mechanism of minocycline against vascular cognitive impairment after cerebral ischemia. Methods The rat model with vascular cognitive impairment was established by permanent bilateral common carotid artery occlusion （BCCAO）. The observing time-points were determined at 4, 8 and 16 weeks after BCCAO. Animals were randomly divided into sham-operated group （n = 6）, model group （subdivided into 3 groups： 4 weeks after BCCAO, n = 6; 8 weeks after BCCAO, n = 6; and 16 weeks after BCCAO, n = 6）, and minocycline group （subdivided into 3 groups： 4 weeks after BCCAO, n = 6; 8 weeks after BCCAO, n = 6; and 16 weeks after BCCAO, n = 6）. Minocycline was administered by douche via stomach after BCCAO until sacrifice. Glial fibrillary acidic protein （GFAP） was examined by Western blotting and immunohistochemistry. Levels of cyclooxygenase-2 （COX-2） and nuclear factor-kappaB （NF-κB） were measured by immunohistochemistry. IL-1β and TNF-α levels were tested with ELISA method. Results Levels of GFAP, COX- 2, NF-κB, IL-1β and TNF-α were all up-regulated after permanent BCCAO, which could be significantly inhibited by minocycline. Conclusion Minocycline could ameliorate the inflammation and oxidative stress in the hippocampus of the vascular cognitive impairment rat model.