大蒜素减轻OSAHS模型大鼠学习能力下降及海马神经元凋亡  

Allicin alleviates the decline in the learning ability and neuronal apoptosis in hippocampus of OSAHS model rats

作　　者：王超[1] 耿彩虹[1] 赵昆朋 嵇朋 WANG Chao∗;GENG Cai-hong;ZHAO Kun-peng;JI Peng(Department of Sleep Medicine,the Second Affiliated Hospital of Xinxiang Medical College,Xinxiang 453002;Department of Neurology,Zhengzhou Third People’s Hospital,Zhengzhou 450000,China)

机构地区：[1]新乡医学院第二附属医院睡眠医学科,河南新乡453002 [2]郑州市第三人民医院神经内科,河南郑州450000

出　　处：《基础医学与临床》2022年第10期1533-1538,共6页Basic and Clinical Medicine

基　　金：河南省科技攻关项目(182102310172)。

摘　　要：目的探讨大蒜素对大鼠阻塞性睡眠呼吸暂停低通气综合征(OSAHS)学习能力下降及海马神经元凋亡的影响。方法将大鼠分为对照组、模型组、大蒜素低剂量(10 mg/kg)和高剂量(40 mg/kg)组、阳性药物组(莫达非尼,20 mg/kg),各18只。Morris水迷宫法判断大鼠学习能力;HE和TUNEL染色观察海马组织病变和神经元凋亡指数(AI);ELISA检测海马组织肿瘤坏死因子(TNF⁃α)、白细胞介素⁃6(IL⁃6)、晚期糖基化终末产物(AGEs)水平;RT⁃qPCR检测糖基化终末产物受体(RAGE)、核转录因子κB(NF⁃κB)p65、B淋巴细胞瘤⁃2基因(Bcl⁃2)、Bcl⁃2相关X蛋白(Bax)mRNA表达;Western blot检测RAGE、NF⁃κB p65、p⁃NF⁃κB p65、Bcl⁃2、Bax蛋白表达。结果与对照组比较,模型组逃逸潜伏期延长,标象限行驶时间缩短,跨平台次数减少,TNF⁃α、IL⁃6、AGEs、AI、RAGE、Bax mRNA和RAGE、p⁃NF⁃κB p65、Bax蛋白表达升高,Bcl⁃2 mRNA和蛋白表达降低(P<0.05);与模型组比较,大蒜素低、高剂量组、阳性药物组的上述变化显著缓解。HE结果显示,与模型组比较,各治疗组海马神经元损伤改善明显。结论大蒜素能有效改善OSAHS大鼠学习能力,降低海马神经元凋亡,可能通过AGEs⁃RAGE/NF⁃κB轴及凋亡因子相关mRNA和蛋白表达发挥作用。Objective To investigate the effect of allicin on the reduction of learning ability and hippocampal neu⁃ronal apoptosis of obstructive sleep apnea⁃hypopnea syndrome(OSAHS)in rats.Methods The rats were divided into control group,model group,low⁃dose(10 mg/kg)and high⁃dose(40 mg/kg)of allicin group as well as posi⁃tive drug group(modafinil,20 mg/kg)with 18 in each.Morris water maze method was used to evaluate the learn⁃ing ability of rats.HE and TUNEL staining microscopy was used to observe hippocampal tissue lesions and neuron apoptosis index(AI).ELISA method was used to detect tumor necrosis factor(TNF⁃α)and interleukin⁃6(IL⁃6)and advanced glycation end products(AGEs)in hippocampal tissue.RT⁃qPCR was used to detect advanced glyco⁃sylation end product⁃specific receptor(RAGE),nuclear transcription factorκB(NF⁃κB)p65,B cell lymphoma⁃2(Bcl⁃2),Bcl⁃2 associated X protein(Bax)mRNA expression.Western blot was used to detect RAGE,NF⁃κB p65,p⁃NF⁃κB p65,Bcl⁃2 and Bax protein.Results Compared with the control group,the escape latency was lon⁃ger,travel time was shorter,cross⁃platform times was reduced.The expressions of TNF⁃α,IL⁃6,AGEs,AI,RAGE,Bax mRNA and RAGE,p⁃NF⁃κB p65,Bax protein were increased while Bcl⁃2 mRNA and protein expres⁃sion decreased in the model group(P<0.05).Compared with the model group,the above changes in the low⁃dose,high⁃dose allcin and positive drug group were significantly alleviated.HE results showed that the damage of hipp⁃ocampal neurons in each treatment group was significantly mitigated.Conclusions Allicin can effectively improve learning ability and reduce apoptosis of hippocampal neurons in OSAHS rats,which may play a role through AGEs⁃RAGE/NF⁃κB axis and apoptosis⁃related mRNA and protein expression.

关 键 词：阻塞性睡眠呼吸暂停低通气综合征 大蒜素 晚期糖基化终末产物 糖基化终末产物受体 核转录因子 

分 类 号：R563[医药卫生—呼吸系统]