豆腐果苷对Aβ_(1-42)诱导阿尔茨海默病模型大鼠认知功能的影响  

Effect of Helicid on cognitive function in Aβ_(1-42) induced Alzheimer's disease model rats

作　　者：汪琴琴 罗潇潇 赵健 丁见 汪萌芽[3] 郑兰荣[1] 郑超[4] WANG Qinqin;LUO Xiaoxiao;ZHAO Jian;DING Jian;WANG Mengya;ZHENG Lanrong;ZHENG Chao(Developmental biology laboratory,Wuhu 241002,China;School of basic medicine;Cell electrophysiology laboratory;Neurobiology laboratory,Wannan Medical College)

机构地区：[1]皖南医学院发育生物学研究室,安徽芜湖241002 [2]皖南医学院基础医学院 [3]皖南医学院细胞电生理研究室 [4]皖南医学院神经生物学研究室

出　　处：《包头医学院学报》2024年第5期12-16,27,共6页Journal of Baotou Medical College

基　　金：安徽省自然科学基金面上项目(2108085MC91);安徽省高校学科拔尖人才学术资助项目(gxbjZD2021061)。

摘　　要：目的:探究豆腐果苷(HEL)对β淀粉样蛋白1-42(Aβ_(1-42))诱导阿尔茨海默病(AD)大鼠认知功能的影响。方法:24只SPF级健康雄性SD大鼠随机分成生理盐水(NS)组、Aβ_(1-42)+NS组、Aβ_(1-42)+HEL组、HEL组,每组6只。通过脑立体定位双侧海马区注射Aβ_(1-42)(5μg/μL)建立AD模型,注射3 d后Aβ_(1-42)+NS组和Aβ_(1-42)+HEL组分别给予生理盐水和豆腐果苷(50 mg/kg)灌胃治疗4周;作为对照,NS组和HEL组分别给予生理盐水和豆腐果苷(50 mg/kg)灌胃4周。治疗结束后通过Morris水迷宫实验对各组大鼠行为、认知能力进行评估;通过HE染色检测各组大鼠海马CA1区细胞的形态变化;采用免疫组化检测大鼠海马CA1区核因子-κB(NF-κB)表达情况;免疫印迹检测大鼠海马中淀粉前体样蛋白(APP)、NF-κB、肿瘤坏死因子(TNF-α)的表达水平。结果:(1)与NS组相比,Aβ_(1-42)+NS组大鼠逃逸潜伏期明显延长,穿越原平台次数和停留在原平台象限的时间均显著降低;海马CA1区细胞形态发生明显核固缩;APP、NF-κB、TNF-α表达显著升高(P<0.05)。(2)与Aβ_(1-42)+NS组相比,Aβ_(1-42)+HEL组大鼠逃逸潜伏期明显缩短,穿越原平台次数和原平台所在象限停留时间均明显增多。(3)海马CA1区细胞核固缩得到良好改善;APP、NF-κB、TNF-α表达明显降低(P<0.05)。(4)NS组和HEL组大鼠Morris水迷宫结果无显著差异,APP、NF-κB和TNF-α蛋白在海马CA1区均无明显变化。结论:豆腐果苷能够改善Aβ_(1-42)诱导AD大鼠认知功能,可能与抑制APP、NF-κB及TNF-α的蛋白表达有关。Objective:To investigate the effects of helicid(HEL)on cognitive function of Aβ_(1-42) induced Alzheimer's disease(AD)rats.Methods:Twenty-four healthy male SD rats were randomly divided into Normal saline(NS)group,Aβ_(1-42)+NS group,Aβ_(1-42)+HEL group and HEL group,with 6 rats in each group.The AD model was established by injecting Aβ_(1-42)(5μg/μL)into the hippocampus of brain stereotaxic injection.After 3 days of injection,Aβ_(1-42)+NS group and Aβ_(1-42)+HEL group were given normal saline and Helicid(50 mg/kg)for 4 weeks.NS group and HEL group were given normal saline and Helicid(50 mg/kg)for 4 weeks,respectively.After treatment,the behavior and cognitive ability of rats in each group were evaluated by Morris water maze test.HE staining was used to detect the morphological changes of Hippocampal CA1 cells in each group.The expression of nuclear factor-κB(NF-κB)in hippocampal CA1 region was detected by Immunohistochemistry.Western blot was used to detect the protein expressions of(amyloiol protein precursor,APP),NF-κB and TNF-α in Hippocampal CA1.Results:Aβ_(1-42)+NS group’s escape latency was increased significantly more than the NS group,through the original times and stay in the original platform quadrant were significantly decreased.Hippocampal CA1 cell morphology showed obvious pyknosis;The expressions of APP,NF-κB and TNF-α were obviously increased(P<0.05).Compared with the Aβ_(1-42)+NS group,the escape latency of rats in the Aβ_(1-42)+HEL group was obviously decreased,the number of crossing the platform and the residence time in the target quadrant were significantly increased.Pyknosis of nucleus in Hippocampal CA1 was improved.The expressions of APP,NF-κB and TNF-α were obviously decreased(P<0.05).There was no significant difference in Morris water maze results between NS group and HEL group.APP,NF-κB and TNF-α proteins had no distinct changes in Hippocampal CA1.Conclusions:Helicid can improve the cognitive function of AD rats induced by Aβ_(1-42),which may be related to the inh

关 键 词：豆腐果苷 β淀粉样蛋白1-42 NF-ΚB 海马 

分 类 号：R285.5[医药卫生—中药学]