6-姜酚通过调节Wnt/β-catenin信号通路对Aβ诱导的AD大鼠细胞凋亡、氧化应激和神经炎症的影响  

6-gingerol relieves cell apoptosis,oxidative stress and neuroinflammation in rats with Alzheimer's disease by activating Wnt/β-catenin signaling pathway

作　　者：李交 肖友元 谢沁 马天蓉 李剑萍 段俊 苏懋 Li Jiao;Xiao Youyuan;Xie Qin;Ma Tianrong;Li Jianping;Duan Jun;Su Mao(Dept of Geriatrics,Sichuan Academy of Medical Sciences,Sichuan People′s Hospital,Chengdu 610072;Dept of Rehabilitation Medicine,Sichuan Academy of Medical Sciences,Sichuan People′s Hospital,Chengdu 610072)

机构地区：[1]四川省医学科学院四川省人民医院老年医学科,成都610072 [2]四川省医学科学院四川省人民医院康复医学科,成都610072

出　　处：《安徽医科大学学报》2022年第1期95-100,共6页Acta Universitatis Medicinalis Anhui

基　　金：四川省科技计划项目(编号:2018TD0021)。

摘　　要：目的探究6-姜酚通过调节Wnt/β-catenin信号通路对β-淀粉样蛋白(Aβ)诱导的阿尔茨海默病(AD)大鼠细胞凋亡、氧化应激和神经炎症的影响。方法通过在大鼠双侧大脑的海马体注射Aβ构建AD大鼠模型。大鼠被随机分为6组:对照组、模型组、低剂量6-姜酚组(50 mg/kg)、中剂量6-姜酚组(75 mg/kg)、高剂量6-姜酚组(100 mg/kg)和阳性对照组(盐酸多尼哌齐0.9 mg/kg)。通过神经损伤评分评估大鼠神经损伤程度,干/湿法检测脑含水量,HE染色检测海马体组织学损伤程度。流式细胞术和TUNEL染色检测海马体细胞凋亡。ELISA检测iNOS、IL-6、TNF-α、SOD、GSH-Px和MDA的蛋白水平。其中qRT-PCR和Western blot检测Wnt和β-catenin的mRNA和蛋白相对表达量。结果与模型组相比,在6-姜酚治疗后,神经损伤评分降低,脑含水量减少,细胞凋亡率降低,促炎细胞因子iNOS、IL-6和TNF-α的表达量下调,SOD和GSH-Px的蛋白含量上调,而MDA蛋白含量下调。Wnt和β-catenin的mRNA和蛋白相对表达量均上调。结论6-姜酚通过激活Wnt/β-catenin信号通路缓解AD大鼠细胞凋亡、氧化应激和神经炎症。Objective To investigate the effects of 6-gingerol on amyloidβ-protein(Aβ)induced apoptosis,oxidative stress and neuroinflammation in Alzheimer's disease(AD)rats by regulating Wnt/β-catenin signaling pathway.Methods The rat model of AD was established by injecting Aβinto hippocampus of bilateral brain.The rats were randomly divided into six groups:control group,model group,low-dose 6-gingerol group,medium-dose 6-gingerol group,high-dose 6-gingerol group and positive control group.Nerve injury was evaluated by nerve injury score,brain water content was measured by dry/wet method,and hippocampal histological injury was measured by HE staining.The apoptosis of hippocampal cells was detected by flow cytometry and TUNEL staining.The protein levels of iNOS,IL-6,TNF-α,SOD,GSH-Px and MDA were detected by ELISA.The mRNA and protein relative expression levels of Wnt andβ-catenin were detected by qRT-PCR and Western blot.Results Compared with the model group,after 6-gingerol treatment,nerve injury score decreased,brain water content decreased,the apoptosis rate decreased,the expression of iNOS,IL-6 and TNF-αdecreased,SOD and GSH-Px protein content increased,while MDA protein content decreased.The mRNA and protein relative expression levels of Wnt andβ-catenin were up-regulated.Conclusion 6-gingerol can reduce apoptosis,oxidative stress and neuroinflammation in AD rats by activating Wnt/β-catenin signaling pathway.

关 键 词：6-姜酚 AD大鼠模型 细胞凋亡 氧化应激 神经炎症 WNT/Β-CATENIN信号通路 

分 类 号：R742[医药卫生—神经病学与精神病学]