| 李帅，邓冬，谢抗，杨艺鸣，陈扬，王伟，陈奕君.高蛋氨酸饮食诱导内皮功能障碍致多器官血流灌注减少小鼠模型评价[J].,2023,43(5):597-604 |
| 高蛋氨酸饮食诱导内皮功能障碍致多器官血流灌注减少小鼠模型评价 |
| Evaluation of Mice Model of Multi-organ Blood Perfusion Decrease Caused by Endothelial Dysfunction Induced by High Methionine Diet |
| |
| DOI：10.7661/j.cjim.20230410.011 |
| 中文关键词: 高蛋氨酸饮食 内皮功能障碍 多器官血流灌注减少 微血管功能障碍 模型评价 |
| 英文关键词:high methionine diet endothelial dysfunction decreased blood perfusion in multiple organs microvascular dysfunction model evaluation |
| 基金项目:国家自然科学基金重点项目（No.81930113）；国家中医药传承创新团队项目（No.ZYYCXTD-C-202201）；广东省中医心脾相关病机和方药研究重点实验室（No.2022B1212010012）；广州市基础与应用研究专题（No.SL2023A04J01903） |
|
| Hits: 392 |
| Download times: 243 |
| 中文摘要: |
| 目的 构建多器官血流灌注减少小鼠模型并解析其机制。方法 将小鼠随机分为空白组和模型组。每组8只，通过3%蛋氨酸饲料构建模型。（1）利用激光散斑检测各组小鼠双足、耳廓、大脑、心脏血流灌注量，结合自发交替Y迷宫结果，评估模型有效性；（2）依据网络药理学结果，测定各组小鼠血浆同型半胱氨酸（Hcy）、一氧化氮（NO）、内皮素-1（ET-1）、可溶性细胞间黏附分子-1（sICAM-1）及肿瘤坏死因子-α（TNF-α）水平；（3）结合微舌象分析及全血细胞计数结果，推测其与临床证候的相关性。结果 与空白组比较，造模1 w后模型组小鼠双足血流灌注量减少（P<0.05），2 w时稳定，6 w后该组小鼠耳廓、大脑、心脏血流灌注量均减少（P<0.05），且其血浆Hcy升高（P<0.05），结合自发交替Y迷宫实验自发交替百分比（SPA%）值减少（P<0.05），表明造模成功。网络药理学结果提示成模机制与细胞迁移调节、NO合成、细胞炎症反应通路相关；与空白组比较，模型组血浆NO降低（P<0.05），sICAM-1及TNF-α有升高趋势（P>0.05），血浆ET-1升高（P<0.05）；舌象分析结果表明，6 w后模型组舌象r值及R值减少（P<0.05），G值、B值增加（P<0.05）；同时，中性粒细胞与淋巴细胞计数减少（P<0.05），平均红细胞体积、血红蛋白量升高（P<0.05）。结论 3%蛋氨酸饲料可干预细胞迁移、NO合成、细胞炎症反应诱导内皮功能障碍造成多器官血流灌注减少。该模型也可为进一步构建专属性更强的心脑微血管疾病动物模型提供方法指导。 |
| 英文摘要: |
| Objective To construct a mouse model with reduced blood perfusion in multiple organs and analyze its mechanism. Methods The C57BL/6J mice were randomly divided into blank group and model group.
（1）Using laser speckle to detect the blood perfusion of the feet，auricle，brain，and heart of the mice in each group，combined with the results of the spontaneous alternating Y maze，to evaluate the effectiveness of the model；（2）Based on the results of network pharmacology，the levels of homocysteine（Hcy），nitric oxide（NO），endothelin 1（ET-1），soluble intercellular adhesion molecule-1（sICAM-1），and tumor necrosis α（TNF-α） in plasma of mice in each group were measured；（3）Combined with microtongue image analysis and comprehensive blood count results，the correlation between the animal model and clinical syndromes was speculated. Results Compared with the blank group，the blood perfusion of mice feet in the model group decreased after 1 weeks （P<0.05），and remained stable at 2 weeks. After 6 weeks，the blood perfusion of the auricle，brain，and heart of the mice in the model group all decreased （P<0.05），and the plasma Hcy increased （P<0.05），the SPA% value in the spontaneous alternating Y maze test decreased （P<0.05），indicating that the modeling was successful. The results of network pharmacology implied that the mechanism of animal modeling was associated with cell migration regulation，nitric oxide synthesis，and cellular inflammatory response pathways.Compared with the blank group，the plasma NO of the mice in the model group was significantly decreased （P<0.05），the expression levels of sICAM-1 and TNF-α were slightly increased （P>0.05），and the expression of plasma ET-1 was significantly increased （P<0.05）. The results of tongue image analysis demonstrated that after 6 weeks，the r value and R value of the tongue image in the model group decreased noticeably （P<0.05），the G value and B value increased （P<0.05）；neutrophil and lymphocyte counts decreased significantly （P<0.05），the mean corpuscular volume and hemoglobin both increased （P<0.05）. Conclusions Feeding a 3% methionine diet could reduce multi-organ blood perfusion in mice by interfering with endothelial dysfunction induced by cell migration regulation，nitric oxide synthesis and cellular inflammatory responses. This animal model can also provide guidance for the further construction of more targeted animal models for cardiovascular and cerebrovascular diseases. |
| View Full Text View/Add Comment Download reader |
