长春西汀对慢性脑缺血大鼠神经功能保护机制的研究

Neuroprotective Mechanism of Vinpocetine in Rats with Chronic Cerebral Ischemia

目的探讨长春西汀对慢性脑缺血(CCH)大鼠的神经功能保护机制。方法选取健康雄性Wistar大鼠30只,随机分为假手术组、模型组及长春西汀组,使用双侧颈总动脉永久性阻断法(2VO)建立慢性脑缺血模型,依据随机数字表法分为假手术组、模型组及长春西汀组,每组10只。长春西汀组于2VO术后24 h内给予长春西汀10 mg/kg腹腔内注射,假手术组、模型组给予等量生理盐水注射,共21 d。采用酶联免疫吸附试验(ELISA)测定各组大鼠脑组织匀浆中白细胞介素-1β(IL-1β)、白细胞介素-10(IL-10)、肿瘤坏死因子-α(TNF-α)含量;使用免疫组化法检测大鼠海马区组织中勿动蛋白(Nogo-A)、少突胶质髓鞘糖蛋白(OMgp)、髓鞘相关糖蛋白(MAG)表达情况;采用免疫组化法检测各组大鼠海马CA1区脑源性神经生长因子(BDNF)及血管内皮生长因子(VEGF)表达。结果模型组及长春西汀组脑组织匀浆中IL-1β、TNF-α含量均高于假手术组(P<0.05),IL-10含量均低于假手术组(P<0.05);长春西汀组大鼠脑组织匀浆中IL-1β、TNF-α含量低于模型组(P<0.05),IL-10含量则高于模型组(P<0.05);假手术组及长春西汀组大鼠海马组织中Nogo-A、OMgp、MAG表达均低于模型组(P<0.05);长春西汀组大鼠海马组织中Nogo-A、OMgp、MAG表达高于假手术组(P<0.05);假手术组及长春西汀组大鼠海马CA1区BDNF及VEGF表达均高于模型组(P<0.05);长春西汀组大鼠海马CA1区BDNF及VEGF表达低于假手术组(P<0.05)。结论长春西汀通过抑制慢性脑缺血大鼠炎性反应及大脑海马区Nogo-A、OMgp、MAG的表达,促进大鼠海马CA1区BDNF及VEGF表达,从而发挥神经保护作用。

Objective To investigate the protective mechanism of vinpocetine on neuroprotective function in rats with chronic cerebral hypoperfusion(CCH).Methods Thirty healthy male Wistar rats were randomly divided into sham operation group,model group,and vinpocetine group,with 10 rats in each group.The CCH model was established by bilateral common carotid artery permanent occlusion(2VO).The rats in vinpocetine group were given intraperitoneal injection of vinpocetine 10 mg/kg within 24 hours after 2VO,and the rats in sham operation group and model group were given the same amount of normal saline for 21 days.Interleukin-1β(IL-1β),interleukin-10(IL-10),and tumor necrosis factor-α(TNF-α)were measured by enzyme-linked immunosorbent assay(ELISA)in brain tissue homogenate.Immunohistochemistry was used to detect the expression of Nogo-A,OMgp,myelin-associated glycoprotein(MAG),brain derived neurotrophic factor(BDNF)in hippocampal CA1 region,and vascular endothelial growth factor(VEGF).Results The contents of IL-1βand TNF-αin the brain tissue homogenate of model group and vinpocetine group were higher than those in sham operation group(P<0.05),and IL-10 content was lower than that in sham operation group(P<0.05).The contents of IL-1βand TNF-αin brain tissue homogenate of vinpocetine group were lower than those of model group(P<0.05),and IL-10 content of vinpocetine group was lower than that of model group(P<0.05).The expression levels of Nogo-A,OMgp,and MAG in hippocampus of rats in sham operation group and vinpocetine group were lower than those in model group(P<0.05).The expression levels of Nogo-A,OMgp,and MAG in hippocampus of rats in vinpocetine group were higher than those in sham operation group(P<0.05).The expression levels of BDNF and VEGF in hippocampal CA1 area of sham operation group and vinpocetine group were higher than those of model group(P<0.05).The expression lvels of BDNF and VEGF in hippocampal CA1 area of rats in vinpocetine group were lower than those of sham operation group(P<0.05).Conclusion Vinoxetine can inhibite the inflammatory response and the expression of NOGO-A,OMgp,and MAG in the hippocampal area of rats with chronic cerebral ischemia,promote the expression of BDNF and VEGF in the hippocampal CA1 area of rats,and play a neuroprotective role.