摘要
背景:基于江西省中医院20多年脑瘫饮的临床用药经验,已证实脑瘫饮治疗脑瘫的有效性及安全性,但是作用机制尚未明确。目的:探讨脑瘫饮对雌雄脑瘫幼鼠肠道菌群、神经细胞与神经递质、运动功能障碍的作用及关联性。方法:采用宫内感染与缺氧处理联合出生后运动限制构建SD幼鼠脑瘫模型,模型组与给药组在造模后分别灌胃生理盐水与脑瘫饮,给药15 d。通过悬吊实验与斜坡实验检测行为学,苏木精-伊红染色和尼氏染色观察脑组织病理变化,ELISA法检测神经递质水平,16S rDNA高通量测序肠道菌群。结果与结论:①与模型组相比,给药组斜坡和悬吊行为学能力增强(P<0.01);②与模型组相比,给药组海马体、大脑皮质中神经元细胞和尼氏小体数量增多;③在海马体中,与模型组相比,给药组乙酰胆碱水平升高(雄鼠:P<0.05;雌鼠:P>0.05),乙酰胆碱酶水平降低(雄鼠:P<0.01;雌鼠:P<0.01),去甲肾上腺素水平升高(雄鼠:P<0.05;雌鼠:P<0.001),5-羟色胺水平升高(雄鼠:P<0.05;雌鼠:P>0.05);④在大脑皮质中,与模型组相比,给药组乙酰胆碱水平升高(雄鼠:P<0.05;雌鼠:P>0.05),乙酰胆碱酶水平降低(雄鼠:P<0.05;雌鼠:P>0.05),去甲肾上腺素水平升高(雄鼠:P<0.01;雌鼠:P<0.05),5-羟色胺水平升高(雄鼠:P<0.01;雌鼠:P<0.01);⑤与模型组相比,给药组肠道菌群中norank_f__Oscillospiraceae属、大肠杆菌属、norank_f__Muribaculaceae属与乳酸杆菌属菌群的种类与丰度显著改善;脑瘫饮所改善肠道菌群的种类与丰度在雌雄鼠之间呈现显著性差异。由此可知,临床经验方脑瘫饮可以通过调整肠道菌群结构与丰度,促进脑组织神经元与尼氏小体的发育、影响神经递质水平,进而有效改善脑瘫幼鼠的运动功能障碍,形成了“肠-脑-肌”轴关联。
BACKGROUND:Based on over 20 years of clinical experience with cerebral palsy decoction at Jiangxi Provincial Hospital of Traditional Chinese Medicine,its efficacy and safety have been confirmed in the treatment of cerebral palsy,but the underlying mechanisms remain unclear.OBJECTIVE:To investigate the effects and correlations of cerebral palsy decoction on gut microbiota,neural cells and neurotransmitters,as well as motor dysfunction in both female and male young rats with cerebral palsy.METHODS:The cerebral palsy model was prepared in Sprague-Dawley young rats subjected to intrauterine infection and hypoxia combined with postnatal movement restriction.After modeling,the model group and the administration group were administered normal saline and cerebral palsy decoction via gavage,respectively.Administration in each group lasted 15 days.Behavioral performance was assessed using the suspension test and slope test.Pathological changes in brain tissue were observed through hematoxylin-eosin staining and Nissl staining.Neurotransmitter levels were measured using ELISA,and gut microbiota was analyzed by 16S rDNA high-throughput sequencing.RESULTS AND CONCLUSION:(1)Compared with the model group,the administration group showed enhanced behavioral abilities in slope and suspension tests(P<0.01).(2)Compared with the model group,the number of neuronal cells and Nissl bodies in the hippocampus and cerebral cortex increased in the administration group.(3)In the hippocampus,compared with the model group,the administration group exhibited elevated acetylcholine levels(male:P<0.05;female:P>0.05),decreased acetylcholinesterase levels(male:P<0.01;female:P<0.01),increased norepinephrine levels(male:P<0.05;female:P<0.001),and elevated serotonin levels(male:P<0.05;female:P>0.05).(4)In the cerebral cortex,compared with the model group,the administration group showed increased acetylcholine levels(male:P<0.05;female:P>0.05),decreased acetylcholinesterase levels(male:P<0.05;female:P>0.05),elevated norepinephrine levels(male:P<0.01;female:P<0.05),and increased serotonin levels(male:P<0.01;female:P<0.01).(5)Compared with the model group,the administration group demonstrated significant improvements in the diversity and abundance of gut microbiota,including the genera norank_f__Oscillospiraceae,Escherichia,norank_f__Muribaculaceae,and Lactobacillus.The improvements in gut microbiota diversity and abundance showed significant differences between male and female rats.These findings indicate that the clinical empirical formula,cerebral palsy decoction,can effectively improve motor dysfunction in young rats with cerebral palsy by modulating the structure and abundance of gut microbiota,promoting the development of neurons and Nissl bodies in brain tissues,and influencing neurotransmitter levels.This establishes a“gut-brain-muscle”axis association.
作者
邹玉雄
刘晓蒙
刘英
朱玥
李书明
郭芳阳
庾馨予
聂鹤云
刘潜
敖梅英
Zou Yuxiong;Liu Xiaomeng;Liu Ying;Zhu Yue;Li Shuming;Guo Fangyang;Yu Xinyu;Nie Heyun;Liu Qian;Ao Meiying(Discipline of Chinese and Western Integrative Medicine,Integrated Chinese and Western Medicine Institute for Children Health&Drug Innovation,Jiangxi University of Chinese Medicine,Nanchang 330004,Jiangxi Province,China;Affiliated Hospital of Jiangxi University of Chinese Medicine,Nanchang 330000,Jiangxi Province,China)
出处
《中国组织工程研究》
北大核心
2026年第16期4054-4066,共13页
Chinese Journal of Tissue Engineering Research
基金
国家自然科学基金项目(82060658),项目负责人:敖梅英
全国重点实验室自主部署重点研发计划项目(20243BCC31008),项目负责人:刘潜
江西中医药大学科研培育项目(2023ZDPY001),项目负责人:刘潜
中西医结合防治儿童疾病及健康保障创新研究团队(CXTD22014),项目负责人:刘潜
江西中医药大学校级教改项目(2022jzyx-2),项目负责人:敖梅英。
关键词
脑瘫
脑瘫饮
雌雄差异
海马体
大脑皮质
神经递质
肠道菌群
16S
rDNA
cerebral palsy
cerebral palsy decoction
male-female differences
hippocampus
cerebral cortex
neurotransmitter
gut microbiota
16S rDNA
