大蒜素通过抑制内质网应激减轻血管性痴呆大鼠海马神经元损伤  

A llicin reduce the damage of hippocampal neurons in rats with vascular dementia by inhibiting endoplasmic reticulum stress

作　　者：陈晨[1] 孙志涛 张洪峰[1] CHEN Chen;SUN Zhi-tao;ZHANG Hong-feng(Department of Scientific Research,Handan Central Hospital,Handan Hebei 056008;No.1 Department of Cardiology,Handan Second Hospital,Handan Hebei 056001)

机构地区：[1]邯郸市中心医院科研科,河北邯郸056008 [2]邯郸市第二医院心内一科,河北邯郸056001

出　　处：《中南药学》2023年第7期1827-1832,共6页Central South Pharmacy

基　　金：邯郸市科学技术研究与发展计划(No.1823208039ZC)。

摘　　要：目的研究大蒜素对血管性痴呆(VD)大鼠海马神经元损伤及内质网应激(ERS)的影响。方法取120只实验用大鼠随机分为6组(n=20):假手术组,模型组,尼莫地平组和低、中、高剂量大蒜素组。除假手术组外,其他5组通过结扎双侧颈总动脉构建VD大鼠模型。低、中、高剂量大蒜素组分别1次·d^(-1)灌胃5、10、20 mg·kg^(-1),尼莫地平组1次·d^(-1)灌胃2 mg·kg^(-1),假手术组和模型组1次·d^(-1)灌胃生理盐水。2周后,进行神经症状评分,HE、TUNEL染色法观察海马神经元病理性变化以及神经元凋亡情况,ELISA法检测海马组织炎症因子(TNF-α、IL-1β和IL-6)水平,Western blot法检测ERS相关蛋白和核因子-κB p65(NF-κB p65)、Caspase-12及Caspase-3蛋白表达。结果与模型组比较,中、高剂量大蒜素组和尼莫地平组大鼠神经症状评分显著降低(P<0.05);海马神经元病理性改变和神经元凋亡状况明显好转;海马组织TNF-α、IL-1β和IL-6含量显著降低(P<0.05),葡萄糖调控蛋白78(GRP78)、C/EBP同源蛋白(CHOP)、NF-κBp65、Caspase-12、Caspase-3相对表达量和内质网激酶磷酸化率(p-PERK/PERK)显著降低(P<0.05)。与尼莫地平组比较,高剂量大蒜素组神经症状评分和TNF-α、IL-6含量显著降低(P<0.05),GRP78、CHOP、NF-κBp65、Caspase-3相对表达量和PERK磷酸化率显著降低(P<0.05)。结论大蒜素可减轻VD大鼠海马神经元凋亡和炎症损伤,其可能的作用机制是抑制ERS。Objective To determine the effect of allicin on the hippocampal neuronal damage and endoplasmic reticulum stress(ERS)in rats with vascular dementia(VD).Methods Totally 120 experimental rats were randomly divided into 6 groups(n=20):a sham operation groups,a model group,a nimodipine group and allicin low,medium,high dose groups.The rat model with VD was established by ligating bilateral common carotid arteries in all groups except the sham operation group.The low,medium,high dose allicin groups were respectively given 5,10,and 20 mg·kg^(-1) by gavage once a day,the nimodipine group was given 2 mg·kg^(-1) by gavage once a day,while the sham operation group and the model group were given normal saline by gavage once a day.Two weeks later,the nerve symptom was scored;the pathological changes and apoptosis of the hippocampal neurons were observed through HE and TUNEL staining;the level of inflammatory factors(TNF-α,IL-1βand IL-6)in the hippocampus were detected by ELISA;the expression of ERS related proteins and nuclear factor-κB p65(NF-κB p65),Caspase-12 and Caspase-3 were detected by Western blot.Results Compared with the model group,the nerve symptom scores of the rats in the medium and high dose allicin groups and the nimodipine group were significantly decreased(P<0.05);the pathological changes of the hippocampal neurons and neuronal apoptosis were significantly improved;the levels of TNF-α,IL-1βand IL-6 in the hippocampus were significantly decreased(P<0.05);and the relative expression of glucose-regulated protein 78(GRP78),C/EBP homologous protein(CHOP),NF-κB p65,Caspase-12,Caspase-3 and the phosphorylation rate of PERK(p-PERK/PERK)were significantly decreased(P<0.05).Compared with the nimodipine group,the nerve symptom scores and the level of TNF-αand IL-6 in the high dose allicin group were significantly decreased(P<0.05),the relative expression of GRP78,CHOP,NF-κB p65,Caspase-3 and the phosphorylation rate of PERK were also significantly decreased(P<0.05).Conclusion Allicin can reduce the apoptosi

关 键 词：大蒜素 血管性痴呆 内质网应激 海马神经元 炎症 凋亡 

分 类 号：R285.5[医药卫生—中药学]