摘要
目的:探讨大蒜素(ALL)对血管性痴呆(VD)大鼠学习记忆能力的影响及其可能的作用机制。方法:采用改良双侧颈总动脉阻断法制备VD大鼠模型,造模成功后随机分为VD组,ALL低剂量组(ALL-L组)和ALL高剂量组(ALL-H组),对假手术组(S组)大鼠进行假手术,每组15只;ALL-L组和ALL-H组造模后分别股静脉注射ALL 5,20 mg·kg-1,S组和VD组注射同体积生理盐水,每天1次,连续2周。治疗完成后用Morris水迷宫实验检测大鼠的学习记忆能力;苏木素-伊红(HE)染色观察海马区脑组织病理特点;检测大鼠脑组织中炎症因子肿瘤坏死因子-α(TNF-α),白细胞介素-6(IL-6),IL-1β的水平和氧化应激反应指标丙二醛(MDA),超氧化物歧化酶(SOD)及谷胱甘肽过氧化物酶(GSH-Px)的含量;末端脱氧核苷酸转移酶介导dUTP缺口末端标记(TUNEL)法检测海马区细胞的凋亡率;蛋白免疫印迹法(Western blot)检测脑组织中凋亡及自噬相关蛋白半胱氨酸天冬氨酸蛋白水解酶-3(Caspase-3),B淋巴细胞瘤-2(Bcl-2),Bcl-2相关X蛋白(Bax),微管相关蛋白1轻链3(LC3)Ⅱ,LC3Ⅰ及自噬关键分子酵母Atg6同系物(Beclin-1)的表达。结果:与VD组比较,ALL-H组及ALL-L组大鼠的学习记忆能力明显优于VD组(P<0.05),海马组织中TNF-α,IL-6,IL-1β水平及MDA含量明显低于VD组(P<0.05),SOD及GSH-Px的活力明显高于VD组(P<0.05),细胞凋亡率明显低于VD组(P<0.05),且ALL-H组较ALL-L组更明显(P<0.05)。ALL-L及ALL-H组海马组织中Caspase-3,Bax,LC3Ⅱ/LC3Ⅰ及Beclin-1表达水平明显低于VD组(P<0.05),Bcl-2表达水平明显高于VD组(P<0.05),且ALL-H组较ALL-L组更明显(P<0.05)。结论:ALL可一定程度上改善VD大鼠的学习记忆能力,其机制可能与对炎症反应、氧化应激、细胞凋亡和自噬的抑制有关。
Objective:To investigate the effect of allicin(ALL)on learning and memory ability of rats with vascular dementia(VD)and the possible mechanism. Method: The VD rats induced by modified bilateral common carotid artery occlusion(BCCAO)were randomly divided into the VD group,low-and high-dose ALL(ALL-L and ALL-H)groups,and the sham operation(S)group,with 15 rats in each group. In the ALL-L and ALL-H groups,ALL was injected into the femoral vein at 5 mg·kg-1 and 20 mg·kg-1,respectively,while the same volume of normal saline was injected in the S and VD groups,once a day,for two successive weeks.Morris water maze(MWM)was used to test the learning and memory ability of rats. Hematoxylin and eosin(HE)staining was conducted to observe the pathological changes in hippocampal tissue,followed by the detection of inflammatory factors tumor necrosis factor-α(TNF-α),interleukin-6(IL-6),and IL-1β as well as oxidative stress indexes malondialdehyde(MDA),superoxide dismutase(SOD),and glutathione peroxidase(GSH-Px)in rat hippocampus. The apoptosis of hippocampal cells was detected by TdT-mediated dUTP Nick end Labeling(TUNEL) assay. The expression levels of apoptosis and autophagy-related proteins cysteinyl aspartate-specific protease-3(Caspase-3),B-cell lymphoma 2(Bcl-2),Bcl-2-associated X protein(Bax),microtubule-associated protein light chain 3 Ⅱ(LC3 Ⅱ ),LC3 Ⅰ,and the mammalian homolog of yeast ATG6(Beclin 1)in hippocampus were determined by Western blot. Result: The comparison with the VD group revealed that the learning and memory abilities of rats in the ALL-H and ALL-L groups were significantly improved(P<0.05). The TNF-α,IL-6,IL-1β,and MDA levels in hippocampus were lowered(P<0.05),whereas the SOD and GSH-Px activities were enhanced(P<0.05). The apoptosis rates were declined(P<0.05),with an even lower rate noticed in the ALL-H group(P<0.05). The expression levels of Caspase-3,Bax,LC3Ⅱ/LC3 Ⅰ ratio,and Beclin-1 in the ALL-H and ALL-L groups were significantly down-regulated in contrast to those in the VD grou
作者
周伟
刘志刚
宋卫中
王建军
ZHOU Wei;LIU Zhi-gang;SONG Wei-zhong;WANG Jian-jun(Henan University,Kaifeng 415000,China;The First Affiliated Hospital of Henan University,Kaifeng 415000,China)
出处
《中国实验方剂学杂志》
CAS
CSCD
北大核心
2021年第12期82-88,共7页
Chinese Journal of Experimental Traditional Medical Formulae
基金
河南省教育厅科学技术研究重点项目(14B320008)。
