黄蒲通窍胶囊对阿尔茨海默病模型大鼠JNK信号通路蛋白及炎性因子表达的影响
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摘要
目的:研究黄蒲通窍胶囊对阿尔茨海默病(AD)模型大鼠JNK信号通路蛋白及炎性因子表达的影响,探讨其治疗AD的作用机制。方法:48只SD大鼠随机分为假手术组(Sham组)、模型组(Model组)、黄蒲通窍组(HPTQ组)和多奈哌齐组(Don组),每组12只。除Sham组外,其余各组采用大鼠腹腔注射D-半乳糖联合双侧海马注射β-淀粉样肽25-35(β-amyloid peptide 25-35,Aβ25-35)建立AD动物模型。各组采取相应干预28d。采用Morris水迷宫法测试大鼠逃避潜伏期,HE染色观察大鼠海马CA3区神经元损伤情况,ELISA法检测大鼠血清IL-1β、TNF-α含量,Western Blot法检测大鼠海马组织JNK、p-JNK含量。结果:与Sham组比较,Model组大鼠逃避潜伏期明显延长(P<0.01),海马CA3区神经元损伤明显,IL-1β、TNF-α含量明显升高(P<0.01),JNK及P-JNK蛋白表达显著增强(P<0.01);与Model组比较, HPTQ、Don组大鼠逃避潜伏期明显缩短(P<0.01),海马CA3区神经元损伤较轻,IL-1β、TNF-α含量明显降低(P<0.01),JNK及P-JNK蛋白表达明显减弱(P<0.01,P<0.05)。结论:中药黄蒲通窍胶囊可抑制JNK信号转导通路异常激活,控制血清中的炎性因子,改善AD大鼠海马神经元损伤。
Objective: To study the effects of Huangpu Tongqiao Capsule on the expression of JNK signaling pathway proteins and inflammatory factors in rats with Alzheimer's disease(AD), and to explore the mechanism of Huangpu Tongqiao Capsule in treatment of AD. Methods: A total of 48 SD rats were randomly divided into sham group, model group, HPTQ group and Donepezil group, with 12 rats in each group. Except Sham group, AD animal models were established by intraperitoneal injection of D-galactose combination with bilateral injection of Aβ25-35 into hippocampus. Each group was intervened for 28 days. Morris water maze method was used to test the escape latency of rats, HE staining was intended to observe the damage of neurons in hippocampal CA3 area of rats, ELISA was aimed at detecting the contents of IL-1β and TNF-α in serum of rats,while Western Blot was used to detect the contents of JNK and p-JNK in hippocampal tissue of rats. Results: Compared with Sham group, the escape latency of model group was significantly prolonged(P<0.01); the neurons in hippocampal CA3 area were damaged evidently; the contents of IL-1β and TNF-αwere significantly increased(P<0.01); the expressions of JNK and p-JNK protein were dramatically increased(P<0.01). Compared with model group, the escape latency of HPTQ and Don group were significantly shortened(P<0.01); the neurons in hippocampal CA3 area were damaged slightly; the contents of IL-1β and TNF-α were significantly decreased(P<0.01); and the contents of JNK and p-JNK protein were significantly decreased(P<0.01,P<0.05). Conclusion: Huangpu Tongqiao Capsule could inhibit abnormal activation of JNK signal transduction pathway, reduce the expression inflammatory factors in serum and improve hippocampal neuron injury in AD rats.
Objective: To study the effects of Huangpu Tongqiao Capsule on the expression of JNK signaling pathway proteins and inflammatory factors in rats with Alzheimer's disease(AD), and to explore the mechanism of Huangpu Tongqiao Capsule in treatment of AD. Methods: A total of 48 SD rats were randomly divided into sham group, model group, HPTQ group and Donepezil group, with 12 rats in each group. Except Sham group, AD animal models were established by intraperitoneal injection of D-galactose combination with bilateral injection of Aβ25-35 into hippocampus. Each group was intervened for 28 days. Morris water maze method was used to test the escape latency of rats, HE staining was intended to observe the damage of neurons in hippocampal CA3 area of rats, ELISA was aimed at detecting the contents of IL-1β and TNF-α in serum of rats,while Western Blot was used to detect the contents of JNK and p-JNK in hippocampal tissue of rats. Results: Compared with Sham group, the escape latency of model group was significantly prolonged(P<0.01); the neurons in hippocampal CA3 area were damaged evidently; the contents of IL-1β and TNF-αwere significantly increased(P<0.01); the expressions of JNK and p-JNK protein were dramatically increased(P<0.01). Compared with model group, the escape latency of HPTQ and Don group were significantly shortened(P<0.01); the neurons in hippocampal CA3 area were damaged slightly; the contents of IL-1β and TNF-α were significantly decreased(P<0.01); and the contents of JNK and p-JNK protein were significantly decreased(P<0.01,P<0.05). Conclusion: Huangpu Tongqiao Capsule could inhibit abnormal activation of JNK signal transduction pathway, reduce the expression inflammatory factors in serum and improve hippocampal neuron injury in AD rats.
引文
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[11]杨希茜,赖星,刘玲.从肾虚痰瘀论老年性痴呆.湖北中医杂志,2016,38(10):44-45
[12]蔡标,谢道俊,王艳,等.黄蒲通窍胶囊对阿尔茨海默病大鼠海马氧化应激和线粒体凋亡途径的影响.中国中西医结合杂志,2018,38(6):707-711
[13]蔡标,叶树,王艳,等.黄蒲通窍胶囊对阿尔茨海默病细胞模型细胞凋亡的影响.中国中药杂志,2018,43(11):2378-2383
[2]Seungeun Lee,Kumju Youn,Dong Hyum Kim,et al.AntiNeuroinflammatory Property of Phlorotannins from Ecklonia cava on A25-35-Induced Damage in PC12 Cells.Mar Drugs,2019,doi:10.3390/md17010007
[3]梁跃霞,曹国琼,张文生.阿尔茨海默症炎症反应及中药干预研究进展.中国药理学通报,2017,33(5):597-602
[4]Yan Wang,Biao Cai,Jing Shao,et al.Genistein suppresses the mitochondrial apoptotic pathway in hippocampal neurons in rats with Alzheimer’s disease.Neural Regen Res,2016,11(7):1153-1158
[5]侯雪芹,陈云波,程淑意,等.补肾益智提取物对AD小鼠空间学习记忆及氧化应激-凋亡相关机制的研究.中华中医药杂志,2015,30(5):1640-1643
[6]李娟,常子嵩,姚遥,等.黄芪甲苷对阿尔茨海默病小鼠模型认知功能和脑内神经炎症的影响.南京中医药大学学报,2018,34(6):597-601
[7]Tianjiao Xu,Chengu Niu,Xiaojie Zhang,et al.β-Ecdysterone protects SH-SY5Y cells againstβ-amyloid-induced apoptosis via c-Jun N-terminal kinase-and Akt-associated complementary pathways.Lab Invest,2018,98(4):489-499
[8]Shiyu Gao,Jianwei Lin,Tianqi Wang,et al.Qingxin kaiqiao fang ameliorates memory impairment and inhibits apoptosis in APP/PS1 double transgenic mice through the MAPK pathway.Drug Des Devel Ther,2019,13:459-475
[9]Arpita Ray,Sean D Speese,Mary A Logan.Glial Draper Rescues AβToxicity in a Drosophila Model of Alzheimers Disease.Neurosci,2017,37(49):11881-11893
[10]侯江淇,郭蕾,张俊龙.阿尔茨海默病中医辨治探析.辽宁中医杂志,2017,44(2):262-264
[11]杨希茜,赖星,刘玲.从肾虚痰瘀论老年性痴呆.湖北中医杂志,2016,38(10):44-45
[12]蔡标,谢道俊,王艳,等.黄蒲通窍胶囊对阿尔茨海默病大鼠海马氧化应激和线粒体凋亡途径的影响.中国中西医结合杂志,2018,38(6):707-711
[13]蔡标,叶树,王艳,等.黄蒲通窍胶囊对阿尔茨海默病细胞模型细胞凋亡的影响.中国中药杂志,2018,43(11):2378-2383