Ganoderma lucidum Triterpenoids (GLTs) Reduce Neuronal Apoptosis via Inhibition of ROCK Signal Pathway in APP/PS1 Transgenic Alzheimer’s Disease Mice
Ganoderma lucidum Triterpenoids (GLTs) Reduce Neuronal Apoptosis via Inhibition of ROCK Signal Pathway in APP/PS1 Transgenic Alzheimer’s Disease Mice
复制标题
灵芝三萜类化合物 (GLT) 通过抑制 APP/PS1 转基因阿尔茨海默病小鼠的 ROCK 信号通路减少神经元凋亡
DOI：
10.1155/2020/9894037
复制
发表时间：
2020
影响因子：
--
通讯作者：
Yimin Zhu
中科院分区：
文献类型：
--
作者：
Nanhui Yu;Yongpan Huang;Yu Jiang;Lianhong Zou;Xiehong Liu;Sulai Liu;Fang Chen;Jun Luo;Yimin Zhu
阿尔茨海默病（AD）是老年人痴呆症的最常见原因。灵芝三萜（GLTs）具有营养健康益处，并已被证明可以促进健康和长寿，但GLTs对AD损伤的保护作用尚未报道。本研究的目的是阐明GLTs对AD模型小鼠和细胞的生物学作用，并探讨其潜在机制。Morris水迷宫（Morris water maze， MWM）实验检测小鼠认知功能的变化。采用苏木精-伊红（HE）染色观察海马的病理变化。硝酸银染色观察海马神经元缠结（nft）。TUNEL染色法检测小鼠脑组织海马神经元凋亡情况。凋亡相关蛋白Bcl2、Bax和caspase 3/cleaved caspase 3的表达水平；抗氧化蛋白Nrf2、NQO1和HO1；western blot检测ROCK信号通路相关蛋白ROCK2和ROCK1。体内实验表明，5个月大的APP/PS1小鼠空间学习能力受损，glt可以减轻AD小鼠的认知障碍。与正常小鼠相比，APP/PS1小鼠大脑海马严重受损，GLTs可通过抑制细胞凋亡、减轻氧化损伤、使ROCK信号通路失活等途径缓解这一症状。体外细胞实验用a - β25-35诱导海马神经元进入AD模型细胞。GLTs促进细胞增殖，促进超氧化物歧化酶（SOD）表达，抑制丙二醛（MDA）和乳酸脱氢酶（LDH）表达。我们的研究强调GLTs通过抑制ROCK信号通路改善AD患者的认知障碍，减轻神经元损伤，抑制海马组织和细胞凋亡。
Alzheimer’s disease (AD) is the most common cause of dementia among senior citizen. Ganoderma lucidum triterpenoids (GLTs) have nutritional health benefits and has been shown to promote health and longevity, but a protective effect of GLTs on AD damage has not yet been reported. The objective of this research was to elucidate the phylactic effect of GLTs on AD model mice and cells and to explore its underlying mechanisms. Morris water maze (MWM) test was conducted to detect changes in the cognitive function of mice. Hematoxylin‐eosin (HE) staining was applied to observe pathological changes in the hippocampus. Silver nitrate staining was applied to observe the hippocampal neuronal tangles (NFTs). Apoptosis of the hippocampal neurons in mouse brain tissue was determined by TUNEL staining. The expression levels of apoptosis‐related protein Bcl2, Bax, and caspase 3/cleaved caspase 3; antioxidative protein Nrf2, NQO1, and HO1; and ROCK signaling pathway‐associated proteins ROCK2 and ROCK1 were measured by western blot.In vivoexperiments show that 5‐month‐old APP/PS1 mice appeared to have impaired acquisition of spatial learning and GLTs could reduce cognitive impairment in AD mice. Compared to normal mice, the hippocampus of APP/PS1 mouse’s brains was severely damaged, while GLTs could alleviate this symptom by inhibiting apoptosis, relieving oxidative damage, and inactivating the ROCK signaling pathway. Inin vitrocell experiments, Aβ25-35was applied to induce hippocampal neurons into AD model cells. GLTs promoted cell proliferation, facilitated superoxide dismutase (SOD) expression, and inhibited malondialdehyde (MDA) and lactic dehydrogenase (LDH) expression of neurons. Our study highlights that GLTs improve cognitive impairment, alleviate neuronal damage, and inhibit apoptosis in the hippocampus tissues and cells in AD through inhibiting the ROCK signaling pathway.