Wang Guo-Quan, Zhou Peng, Xie Dao-Jun, Ye Shu, Gao Hua-Wu, Wang Yan, Fang Zheng-Qing, Cai Biao
School of Integrated Traditional Chinese and Western Medicine, Anhui University of Chinese Medicine Hefei 230012, China.
School of Integrated Traditional Chinese and Western Medicine, Anhui University of Chinese Medicine Hefei 230012, China Academy of Integrative Medicine, Anhui Academy of Chinese Medicine Hefei 230012, China Key Laboratory of Chinese Medicinal Formula of Anhui Province Hefei 230012, China.
Zhongguo Zhong Yao Za Zhi. 2020 May;45(9):2165-2171. doi: 10.19540/j.cnki.cjcmm.20191219.401.
Huangpu Tongqiao Capsules(HPTQC), with the functions of invigorating Qi and kidney, eliminating phlegm and removing blood stasis, have the effect of treating Alzheimer's disease(AD), but its mechanism needs further exploration. To explore the relationship between the therapeutic mechanism of HPTQC on Alzheimer's disease and EGFR-PLCγ signal pathway, 40 healthy male SD rats were selected and divided into 4 groups randomly: sham operation group(sham), model group(model), HPTQC group(HPTQC), and nimodipine group(NMP). AD rat model was established by intraperitoneal injection of D-galactose combined with an intracerebral injection of amyloid-β peptide(25-35). After 28 days of administration, Morris water maze test and HE staining showed that the learning and memory ability of AD rats were significantly decreased(P<0.01), and hippocampal neurons were obviously da-maged. However, HPTQC could improve the learning and memory ability of AD rats(P<0.05) and reduce the damage of hippocampal neurons. Immunofluorescence test results showed that the expression levels of EGFR and p-Tau in hippocampal CA1 region of AD rats were significantly increased(P<0.01), and HPTQC could reduce the expression of EGFR and p-Tau in hippocampus of AD rats(P<0.01). Western blot results showed that the protein expression levels of EGFR, PLCγ, IP3 R and p-Tau in hippocampus of AD rats were significantly increased(P<0.01), and HPTQC could reduce the protein expression of EGFR, PLCγ, IP3 R and p-Tau in AD rats(P<0.05). RT-PCR results showed that the mRNA levels of EGFR, PLCγ, IP3 R and Tau in hippocampus of AD rats were significantly increased(P<0.01), and HPTQC could reduce the mRNA levels of EGFR, PLCγ, IP3 R and Tau in AD rats(P<0.05). The results indicate that HPTQC can improve the learning and memory ability of AD rats, and its mechanism of action may be related to regulating EGFR-PLCγ signal pathway.
黄埔通窍胶囊(HPTQC)具有益气补肾、化痰祛瘀的功效,对阿尔茨海默病(AD)有治疗作用,但其作用机制有待进一步探索。为探讨HPTQC治疗阿尔茨海默病的作用机制与表皮生长因子受体(EGFR)-磷脂酶Cγ(PLCγ)信号通路的关系,选取40只健康雄性SD大鼠,随机分为4组:假手术组(sham)、模型组(model)、HPTQC组(HPTQC)和尼莫地平组(NMP)。采用腹腔注射D-半乳糖联合脑内注射β淀粉样蛋白(25-35)建立AD大鼠模型。给药28天后,Morris水迷宫试验和HE染色显示,AD大鼠的学习记忆能力显著下降(P<0.01),海马神经元明显受损。然而,HPTQC可提高AD大鼠的学习记忆能力(P<0.05),并减轻海马神经元损伤。免疫荧光检测结果显示,AD大鼠海马CA1区EGFR和磷酸化Tau(p-Tau)的表达水平显著升高(P<0.01),而HPTQC可降低AD大鼠海马中EGFR和p-Tau的表达(P<0.01)。蛋白质免疫印迹结果显示,AD大鼠海马中EGFR、PLCγ、三磷酸肌醇受体(IP3R)和p-Tau的蛋白表达水平显著升高(P<0.01),而HPTQC可降低AD大鼠中EGFR、PLCγ、IP3R和p-Tau的蛋白表达(P<0.05)。逆转录聚合酶链反应(RT-PCR)结果显示,AD大鼠海马中EGFR、PLCγ、IP3R和Tau的mRNA水平显著升高(P<0.01),而HPTQC可降低AD大鼠中EGFR、PLCγ、IP3R和Tau的mRNA水平(P<0.05)。结果表明,HPTQC可提高AD大鼠的学习记忆能力,其作用机制可能与调节EGFR-PLCγ信号通路有关。