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郝兴宇, 谢映, 吴吉, 朱沁泉, 张涤, 蒋屏.归脾丸对粪菌移植造模的孤独症谱系障碍大鼠行为学及脑5-HT含量的影响[J].湖南中医药大学学报英文版,2024,44(6):936-942.[Click to copy
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| 归脾丸对粪菌移植造模的孤独症谱系障碍大鼠行为学及脑5-HT含量的影响 |
| 郝兴宇,谢映,吴吉,朱沁泉,张涤,蒋屏 |
| (湖南中医药大学第一中医临床学院, 湖南 长沙 410208;湖南中医药大学第一附属医院, 湖南 长沙 410007) |
| 摘要: |
| 目的 验证归脾丸改善孤独症谱系障碍（autism spectrum disorder, ASD）子代大鼠核心症状的疗效，观察其对脑5-羟色胺（5-hydroxytryptamine，5-HT）含量的影响，并探讨其疗效与脑5-HT水平的相关性。方法 将10只SPF级SD孕鼠随机分为正常孕鼠组（3只）和粪菌移植（fecal microbiota transplantation，FMT）孕鼠组（7只），FMT孕鼠组通过FMT法进行造模。子代鼠出生第28天时，通过行为学检测筛选符合ASD疾病模型的雄鼠30只，随机分为模型组（等体积生理盐水）、归脾丸低剂量组（0.75 g/kg）、归脾丸中剂量组（1.5 g/kg）、归脾丸高剂量组（3 g/kg）、双歧杆菌组（0.5 g/kg），每组6只；正常雄鼠6只，设置为正常组（等体积生理盐水）。各组连续灌胃14 d，1次/d。记录大鼠体质量；采用行为学检测评估疗效；采用ELISA法测定大鼠前额5-HT含量；等级相关分析法分析子代大鼠社交能力及社交新颖性与5-HT的相关性。结果 与正常孕鼠组比较，FMT孕鼠组子代鼠睁眼时间延长（P<0.05）、体质量下降（P<0.05）。用药前，与正常组比较，模型组社交能力降低（P<0.05）、社交新颖性降低（P<0.05）、焦虑程度增加（P<0.05）。用药2周后，与正常组比较，模型组社交能力降低（P<0.05）、社交新颖性降低（P<0.05）、焦虑程度加重（P<0.05）、体质量及5-HT含量下降（P<0.05）。与模型组比较，各用药组社交能力增强（P<0.05）、社交新颖性增强（P<0.05）、焦虑状态减轻（P<0.05）、5-HT含量增加（P<0.05）；归脾丸中、高剂量组，双歧杆菌组体质量增加（P<0.05）。与归脾丸高剂量组比较，归脾丸低剂量组社交能力降低（P<0.05）、社交新颖性降低（P<0.05），体质量及5-HT含量下降（P<0.05），归脾丸中剂量组5-HT含量下降（P<0.05），双歧杆菌组社交新颖性降低（P<0.05）。相关新分析显示，ASD大鼠社交偏好系数及新颖偏好系数与5-HT含量呈显著正相关（P<0.05）。结论 归脾丸可显著改善FMT子代大鼠的ASD样行为，其机制可能与上调脑内5-HT含量有关。 |
| 关键词: 孤独症谱系障碍 归脾丸 5-羟色胺 粪菌移植法 社交能力 社交新颖性 |
| DOI：10.3969/j.issn.1674-070X.2024.06.002 |
| Received:January 16, 2024 |
| 基金项目:湖南省科学技术厅重点领域研发计划项目（2019SK2081）；湖南省卫生健康委员会科研计划项目（D202306048765）；中医学湖南省世界一流培育学科。 |
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| Effects of Guipi Pill on behavior and brain 5-HT content in rats with autism spectrum disorder modeled by fecal microbiota transplantation |
| HAO Xingyu, XIE Ying, WU Ji, ZHU Qinquan, ZHANG Di, JIANG Ping |
| (The First Clinical School of Chinese Medicine, Hunan University of Chinese Medicine, Changsha, Hunan 410208, China;The First Hospital of Hunan University of Chinese Medicine, Changsha, Hunan 410007, China) |
| Abstract: |
| Objective To verify the efficacy of Guipi Pill in alleviating core symptoms in offspring rats with autism spectrum disorder (ASD), to observe its effects on the content of 5-hydroxytryptamine (5-HT) in the brain, and to explore the correlation between its efficacy and the level of 5-HT in the brain. Methods Ten SPF SD pregnant rats were randomized into normal pregnant group (n=3) and fecal microbiota transplantation (FMT) pregnant group (n=7). The FMT pregnant group was modeled by FMT method. On the 28th day of birth, 30 male rats were screened by behavioral test to meet the ASD disease model. Then they were randomly subdivided into model group (an equal volume of normal saline), the low-, medium-, and high-dose (0.75 g/kg, 1.5 g/kg, 3 g/kg) Guipi Pill groups, and the Bifidobacterium (0.5 g/kg) group, with six rats in each group. In addition, six normal male rats were set as normal group (an equal volume of normal saline). Each group was given intragastric administration for 14 d, once a day. The body weight of rats was recorded, the efficacy was evaluated by behavioral test, the content of 5-HT in the forehead of rats was determined by ELISA, and the correlation between sociability, social novelty and 5-HT in offspring rats was analyzed by rank correlation analysis. Results Compared with the normal pregnant group, the offspring rats in the FMT pregnant group showed longer eye opening time (P<0.05) and lower body weight (P<0.05). Before treatment, compared with the normal group, the model group showed lower sociability (P<0.05) and social novelty (P<0.05) but higher degree of anxiety (P<0.05). After two weeks of medication, compared with the normal group, the model group showed lower sociability (P<0.05), lower social novelty (P<0.05), higher degree of anxiety (P<0.05), and lower body weight and 5-HT content (P<0.05). Compared with the model group, each treatment group showed higher sociability (P<0.05), higher social novelty (P<0.05), lower degree of anxiety (P<0.05), and higher 5-HT content (P<0.05). The body weight of the medium- and high-dose Guipi Pill groups and the Bifidobacterium group increased (P<0.05). Compared with the high-dose Guipi Pill group, the low-dose Guipi Pill group had lower sociability (P<0.05), lower social novelty (P<0.05), and lower body weight and content 5-HT (P<0.05), meanwhile, the medium-dose Guipi Pill group had lower 5-HT content (P<0.05) and the Bifidobacterium group had lower social novelty (P<0.05). Correlation analysis showed that the social preference coefficient and novelty preference coefficient of ASD rats were significantly and positively correlated with 5-HT content (P<0.05). Conclusion Guipi Pill can significantly alleviate ASD-like behavior in FMT offspring rats, and its mechanism may be related to the up-regulation of 5-HT content in the brain. |
| Key words: autism spectrum disorder Guipi Pill 5-hydroxytryptamine fecal microbiota transplantation sociability social novelty |
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