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开心散,一种中药汤剂,通过增强大鼠中性肽链内切酶的表达加速β-淀粉样蛋白的降解。

Kai-Xin-San, a Chinese Herbal Decoction, Accelerates the Degradation of -Amyloid by Enhancing the Expression of Neprilysin in Rats.

作者信息

Wang Na, Jia Yongming, Zhang Bo, Li Yan, Murtaza Ghulam, Huang Shuming, Liu Xuewei

机构信息

Department of Neuropharmacology, College of Pharmacy, Qiqihar Medical University, Qiqihar 161006, China.

Department of Neuroscience, Institute for Traditional Chinese Medicine, Heilongjiang University of Chinese Medicine, Harbin 150040, China.

出版信息

Evid Based Complement Alternat Med. 2020 Feb 21;2020:3862342. doi: 10.1155/2020/3862342. eCollection 2020.

Abstract

This study aimed to investigate the mechanisms of Kai-Xin-San (KXS, a famous Chinese herbal decoction used to treat amnesia) on the degradation of A and further elucidate the mechanism of KXS on A-induced memory dysfunction. After pretreatment with KXS (1.08 g/kg/day) for two weeks, A (2 L, 200 M) was injected into rat hippocampus to induce cognitive dysfunction. Morris water maze (MWM) test was developed to evaluate cognitive performance in rats. Hippocampal neurons were observed by histological staining using Hematoxylin-Eosin (HE) methods. Levels of exogenous A , which was injected into the hippocampus, were continually measured through a special Enzyme-linked immunoassay (ELISA) kit to observe the catabolic process of A in the brain. Similarly, A degradation in PC12 cells was also investigated using the ELISA kit. The expressions of A degeneration enzymes, including neprilysin (NEP), angiotensin-converting enzyme (ACE), and endothelin-converting enzyme (ECE), were detected by western blotting to elucidate A reduction mechanism. Our results showed that KXS prevented A -induced cognitive impairment and attenuated hippocampus neuronal damage caused by A . Moreover, KXS could accelerate A degradation in A injected rats. Furthermore, NEP, an A degradation enzyme, was increased in the hippocampus while ECE and ACE, other two A-degrading enzymes, were not changed. KXS accelerated A degradation in PC12 cells. Our findings revealed that KXS facilitated the degradation of A by increasing the expression of NEP in rat hippocampus. By reducing the A burdens, KXS protected hippocampal neurons, leading to the improvement of cognitive function in rats.

摘要

本研究旨在探讨开心散(KXS,一种用于治疗失忆症的著名中药汤剂)对Aβ降解的作用机制,并进一步阐明开心散对Aβ诱导的记忆功能障碍的作用机制。用开心散(1.08 g/kg/天)预处理两周后,将Aβ(2 μL,200 μM)注入大鼠海马体以诱导认知功能障碍。采用Morris水迷宫(MWM)试验评估大鼠的认知表现。使用苏木精-伊红(HE)方法进行组织学染色观察海马神经元。通过特殊的酶联免疫吸附测定(ELISA)试剂盒持续测量注入海马体的外源性Aβ水平,以观察Aβ在脑内的分解代谢过程。同样,也使用ELISA试剂盒研究PC12细胞中Aβ的降解情况。通过蛋白质免疫印迹法检测Aβ降解酶,包括中性内肽酶(NEP)、血管紧张素转换酶(ACE)和内皮素转换酶(ECE)的表达,以阐明Aβ减少的机制。我们的结果表明,开心散可预防Aβ诱导的认知障碍,并减轻Aβ引起的海马神经元损伤。此外,开心散可加速注射Aβ的大鼠体内Aβ的降解。此外,海马体中Aβ降解酶NEP增加,而另外两种Aβ降解酶ECE和ACE未发生变化。开心散可加速PC12细胞中Aβ的降解。我们的研究结果表明,开心散通过增加大鼠海马体中NEP的表达促进Aβ的降解。通过减轻Aβ负担,开心散保护海马神经元,从而改善大鼠的认知功能。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1da4/7054802/28651d6137ac/ECAM2020-3862342.001.jpg

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