地黄益智方对APP/PS1双转基因小鼠海马神经元凋亡和Nrf2通路蛋白的影响  

Effects of Dihuang Yizhi Formula(地黄益智方)on Apoptosis of Hippocampal Neuronal Cells and Expressions of Proteins in Nrf2 Pathway in APP/PS1 Double Transgenic Mice

作　　者：甄蓉蓉 曲彦洁 顾超[1] 张立敏[1] 胡兵[1] 陈久林[2] 安红梅[1] ZHEN Rongrong;QU Yanjie;GU Chao;ZHANG Limin;HU Bing;CHEN Jiulin;AN Hongmei(Longhua Hospital,Shanghai University of Traditional Chinese Medicine,Shanghai 200032,China;Shanghai Geriatric Institute of Chinese Medicine,Shanghai 200031,China)

机构地区：[1]上海中医药大学附属龙华医院,上海200032 [2]上海市中医老年医学研究所,上海200031

出　　处：《辽宁中医杂志》2022年第1期177-180,221,共5页Liaoning Journal of Traditional Chinese Medicine

基　　金：国家自然科学基金(81873246);国家中医药管理局第四批全国中医(临床、基础)优秀人才研修项目(国中医药人教发[2017]第24号);上海市科委自然科学基金(18ZR1439900)

摘　　要：目的观察地黄益智方对APP/PS1转基因小鼠海马神经元凋亡及Nrf2/ARE通路蛋白表达的影响。方法以APP/PS1双转基因小鼠为阿尔茨海默病模型动物,给予盐酸多奈哌齐(西药组)和地黄益智方干预12周,TUNEL染色检测细胞凋亡,试剂盒检测Caspase-3活性,ELISA检测血清核因子E_(2)相关因子2(Nrf2),血红素加氧酶1(HO-1)和醌氧化还原酶1(NQO1)。结果TUNEL染色发现模型组细胞核皱缩,神经元凋亡多于正常组(P<0.001);西药组及地黄益智方各剂量组凋亡神经元均少于模型组(P<0.01)。模型组Caspase-3活性高于正常组(P<0.001),西药组及地黄益智方各剂量组Caspase-3活性较模型组降低(P<0.05)。模型组Nrf2、HO-1和NQO1蛋白表达均低于正常组,西药组及地黄益智方各剂量组Nrf2、HO-1和NQO1水平升高(P<0.05)。结论地黄益智方可以抑制APP/PS1双转基因阿尔茨海默病小鼠海马神经元凋亡,其机制可能与调控Nrf2/ARE信号通路,上调HO-1和NQO1,抑制Caspase-3活性相关。Objective To observe the effect of Dihuang Yizhi Formula(地黄益智方,DHYZ)on apoptosis of hippocampal neuronal cells and expressions of proteins in Nrf2/ARE pathway in APP/PS1 double transgenic mice.Methods APP/PS1 double transgenic mice were used as Alzheimer's disease(AD)model and treated with Donepezil(western medicine group)and DHYZ for 12 weeks.Apoptosis was identified by TUNEL staining.Caspase-3 activity was detected by commercial kit.Serum nuclear factor E_(2)related factor 2(Nrf2),heme oxygenase-1(HO-1)and NAD(P)H quinone dehydrogenase 1(NQO1)were detected by ELISA.Results TUNEL staining showed that the nucleus of the model group was wrinkled and the apoptosis of neurons was higher than that of the normal group(P<0.001).The number of apoptotic neurons in the western medicine group and DHYZ was lower than that in the model group(P<0.01).The activity of caspase-3 in the model group was higher than that in the normal group(P<0.001),while the activity of Caspase-3 in the western medicine group and the DHTZ groups was lower than that in the model group(P<0.05).The protein expressions of Nrf2,HO-1 and NQO1 in the model group were all lower than those in the normal group,and the levels of Nrf2,HO-1 and NQO1 in the western medicine group and the DHYZ groups were increased(P<0.05).Conclusion DHYZ can inhibit the apoptosis of hippocampal neurons in APP/PS1 double-transgenic AD mice,and its mechanism may be related to the regulation of Nrf2/ARE signaling pathway,up-regulation of HO-1 and NQO1,and inhibition of caspase-3 activity.

关 键 词：阿尔茨海默病 地黄益智方 细胞凋亡 氧化应激 核因子E 相关因子2 血红素加氧酶1 醌氧化还原酶1 

分 类 号：R285.5[医药卫生—中药学]