| 引用本文: | 张运辉,张训浩,杨梦琳,伍大华,刘霞,杨昆,程妍.涤痰汤通过JNK/p53信号通路改善阿尔茨海默病大鼠铁死亡及认知功能障碍的研究[J].中国现代应用药学,2025,42(2):44-53. |
| zhangyunhui,zhangxunhao,yangmenglin,wudahua,liuxia,yangkun,chengyan.Research on the Improvement of Ferroptosis and Cognitive Function Impairment in Alzheimer's Disease Rats by Ditan Decoction via the JNK/p53 Signaling Pathway[J].Chin J Mod Appl Pharm(中国现代应用药学),2025,42(2):44-53. |
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| 涤痰汤通过JNK/p53信号通路改善阿尔茨海默病大鼠铁死亡及认知功能障碍的研究 |
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张运辉1, 张训浩1, 杨梦琳1, 伍大华2, 刘霞1, 杨昆1, 程妍1
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1.重庆三峡医药高等专科学校;2.湖南中医药大学
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| 摘要: |
| 目的 探讨涤痰汤通过调节JNK/p53信号通路来改善阿尔茨海默病(AD)大鼠的铁死亡和认知功能障碍。方法 SPF级雄性SD大鼠60只,随机分为对照组、模型组、涤痰汤低、中、高剂量(2.137, 4.275,8.550 g/kg)组及多奈哌齐阳性对照组(0.00045 g/kg),每组10只。除对照组外,其余组双侧海马注射β淀粉样蛋白(Aβ)25-35造模。灌胃给药1次/d,连续4周。Morris水迷宫实验检测各组逃避潜伏期、跨越平台次数；苏木素-伊红(HE)染色法观察海马区病理形态学变化；透射电镜观察大鼠海马组织中神经元线粒体超微结构变化；流式细胞术检测海马活性氧(ROS)水平；应用生化法检测大鼠海马组织中超氧化物歧化酶(SOD)、谷胱甘肽过氧化物酶(GSH)和丙二醛(MDA)含量；蛋白免疫印迹法(Western blot)及实时荧光定量聚合酶链式反应(RT-qPCR)检测大鼠海马组织c-Jun氨基末端激酶(JNK)、p53、溶质载体家族7 成员 11(SLC7A11)、谷胱甘肽过氧化物酶(GPX4)、铁蛋白重链1(FTH1)、环氧合酶2(COX-2)蛋白及mRNA相对表达水平。结果 与模型组比较,涤痰汤干预后可明显提高模型大鼠的学习、空间记忆能力(P<0.05,P<0.01),减轻海马组织的病理形态学损伤,减轻线粒体损伤,升高SOD、GSH 水平,降低MDA、ROS水平(P<0.05,P<0.01),下调JNK、p53、COX-2蛋白及mRNA的表达(P<0.05,P<0.01),上调SLC7A11、GPX4、FTH1蛋白及mRNA的表达(P<0.05,P<0.01)。结论 涤痰汤可改善AD大鼠认知障碍,其机制可能与通过抑制JNK/p53信号通路抑制铁死亡有关。 |
| 关键词: 涤痰汤 阿尔茨海默病 氧化应激 铁死亡 JNK/p53信号通路 |
| DOI： |
| 分类号:R284.2；R285；R289 ? |
| 基金项目:国家自然科学基金项目（面上项目，重点项目，重大项目） |
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| Research on the Improvement of Ferroptosis and Cognitive Function Impairment in Alzheimer's Disease Rats by Ditan Decoction via the JNK/p53 Signaling Pathway |
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zhangyunhui1, zhangxunhao1, yangmenglin1, wudahua2, liuxia1, yangkun1, chengyan1
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1.Chongqing Three Gorges Medical College;2.Hunan University of Chinese Medicine
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| Abstract: |
| ABSTRACT: OBJECTIVE To Explore Ditan Decoction can modulate the JNK/p53 signaling pathway to improve ferroptosis and cognitive dysfunction in Alzheimer's disease (AD) rats models . METHODS Sixty SPF grade male SD rats were randomly divided into control group,model group, Ditan Decoction low-,moderate-,high- dosage (2.137, 4.275and 8.550 g/kg)groups and donepezil positive control group(0.00045 g/kg),with 10 rats in each group. Except for the control group,the rats in the other groups were injected with β-amyloid (Aβ)25-35 into bilateral hippocampal to establish the model.The drug was given once a day by intragastric administration,for 4 weeks.Morris water maze test to detect escape latency and cross-platform times. The pathomorphological changes of rat hippocampal neurons by hematoxylin-eosin(HE)staining. Transmission electron microscopy was used to observe the ultrastructural changes of mitochondria in rat hippocampal tissues.Flow cytometry was used to detect the level of hippocampal tissues reactive oxygen species (ROS).The content of SOD, GSH and MDA in hippocampal tissue of rat were detected by biochemical method.Western blot and RT-q PCR were used to detect the protein and mRNA levels of c-Jun amino-terminal kinase (JNK),p53,sol-ute carrier family 7 member 11 (SLC7A1),glutathione peroxidase (GPX4), ferritin heavy chain(FTH1) and cyclooxygenase-2(COX-2) in hip-pocampus.RESULTS Compared with the model group, the intervention of Ditan Decoction can significantly improve the learning and spatial memory abilities of model rats (P<0.05, P<0.01), alleviated pathological and morphological damage to hippocampal tissue, reduced mitochondrial damage,increased SOD and GSH level,reduced MDA and ROS level (P<0.05, P<0.01), and Downregulate the expression of JNK, p53, COX-2 proteins and mRNA (P<0.05, P<0.01), Upregulation of SLC7A11, GPX4, FTH1 protein and mRNA expression (P<0.05, P<0.01).CONCLUSION Ditan Decoction can improve the cognitive impairment of AD rats,and its mechanism may be related to the inhibition of ferroptosis by suppressing the JNK/p53 signal pathway. |
| Key words: Ditan Decoction Alzheimer"s disease Oxidative stress Ferroptosis JNK / p53 signaling pathway |
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