Chen Yun, Jiang Lianyan, Li Mao, Shen Yuling, Liu Shanyu, Yang Dongdong
Department of Neurology, Chengdu University of Traditional Chinese Medicine, Sichuan, PR China.
Department of Neurology, The First People's Hospital of Bijie City, Guizhou, PR China.
Heliyon. 2024 Apr 12;10(8):e29556. doi: 10.1016/j.heliyon.2024.e29556. eCollection 2024 Apr 30.
Long-term alcohol consumption can cause organic damage to the brain, resulting in mental and nervous system abnormalities and intellectual impairment. Huanglian Jiedu decoction (HLJDD) is the classic representative of clearing heat and detoxifying. This study aimed to explore the effects and possible mechanisms of HLJDD on brain injury in chronic alcohol-exposed mice.
The alcohol-exposed mice were treated with different doses of HLJDD to observe behavioral changes, hippocampal Aβ deposition, number and ultrastructural changes of neurons in the hippocampus and prefrontal cortex, and expressions of synaptic proteins. On this basis, transcriptome sequencing was used to analyze the differentially expressed genes in different treatment groups, and functional enrichment analysis was performed. Then, WB and RT-PCR were used to verify the expression of the pathway.
Chronic alcohol exposure reduced body weight in mice, led to motor cognitive impairment, increased Aβ in the hippocampus, decreased the number of neurons in the hippocampus and prefrontal cortex, and the expression of PSD95 and SYN in the hippocampus. HLJDD significantly improved the cognitive dysfunction of mice and alleviated the damage of the hippocampus and prefrontal cortex. Transcriptome sequencing results showed that the regulatory effects of HLJDD on chronic alcohol-exposed mice may be related to the RAS pathway. Further experiments confirmed that chronic alcohol exposure caused a significant increase in protein and gene expressions of the RAS-RAF-MEK-ERK pathway in mouse, and this activation was reversed by HLJDD.
HLJDD may ameliorate brain damage caused by chronic alcohol exposure by regulating the RAS-RAF-MEK-ERK pathway.
长期饮酒可导致大脑器质性损伤，引发精神和神经系统异常以及智力损害。黄连解毒汤是清热泻火解毒的经典代表方剂。本研究旨在探讨黄连解毒汤对慢性酒精暴露小鼠脑损伤的影响及可能机制。
对酒精暴露小鼠给予不同剂量的黄连解毒汤进行处理，观察其行为变化、海马区β淀粉样蛋白（Aβ）沉积、海马和前额叶皮质神经元数量及超微结构变化以及突触蛋白表达。在此基础上，采用转录组测序分析不同处理组的差异表达基因，并进行功能富集分析。然后，运用蛋白质免疫印迹法（WB）和逆转录-聚合酶链反应（RT-PCR）验证该通路的表达。
慢性酒精暴露使小鼠体重减轻，导致运动认知功能障碍，海马区Aβ增加，海马和前额叶皮质神经元数量减少，海马区突触后致密蛋白95（PSD95）和突触素（SYN）表达降低。黄连解毒汤显著改善了小鼠的认知功能障碍，减轻了海马和前额叶皮质的损伤。转录组测序结果显示，黄连解毒汤对慢性酒精暴露小鼠的调节作用可能与RAS通路有关。进一步实验证实，慢性酒精暴露导致小鼠RAS-RAF-MEK-ERK通路的蛋白和基因表达显著增加，而黄连解毒汤可逆转这种激活。
黄连解毒汤可能通过调节RAS-RAF-MEK-ERK通路改善慢性酒精暴露所致的脑损伤。
