基于“病-证-药”探讨卒中后抑郁病证结合模型构建及评估  

Establishment and evaluation of a combination of disease and syndrome model of post-stroke depression based on the theory of “disease-syndrome-drug”

作　　者：刘志恒 陈雨立 刘羽[1] 王鑫 刘瑜 刘林[1] LIU Zhiheng;CHEN Yuli;LIU Yu;WANG Xin;LIU Yu;LIU Lin(the First Hospital of Hunan University of Chinese Medicine,Changsha 410007,China;Hunan University of Chinese Medicine,Changsha 410208,China)

机构地区：[1]湖南中医药大学第一附属医院,长沙410007 [2]湖南中医药大学,长沙410208

出　　处：《中国实验动物学报》2025年第3期388-398,共11页Acta Laboratorium Animalis Scientia Sinica

基　　金：湖南省自然科学基金(2023JJ60488,2025JJ80956);湖南省中医药科研项目(B2023129);湖南省重点研发项目(2023DK2005,2024JK2121);湖南省教育厅项目(24B0344)。

摘　　要：目的 基于“郁、瘀、痰”证素探讨卒中后抑郁症(PSD)病证结合模型及其客观评价体系的构建。方法 将大鼠随机分为对照组、抑郁组、卒中组、PSD组、百事乐加味方组。以“大脑中动脉栓塞术(MCAO)+慢性不可预知性温和应激(CUMS)”制备PSD病证结合模型。造模结束后,以水迷宫实验、旷场实验、强迫游泳实验、糖水偏好实验、神经递质水平、脑组织病理损伤、舌质和爪色RGB值、血液流变学、血脂代谢情况分别评估“郁、瘀、痰”证候要素。结果 PSD大鼠目标象限停留时间、穿越平台、爬格及直立次数显著降低,糖水消耗率下降,强迫游泳相对不动时间显著增加;苏木素-伊红(HE)及尼氏染色结果表明PSD大鼠脑组织明显损伤,血清、脑脊液5-HT显著降低、Glu显著升高;舌质和爪色RGB值下降;血液流变学呈高凝;血脂代谢相关指标均明显异常。百事乐加味方组较PSD组,大鼠目标象限停留时间、穿越平台、爬格及直立次数显著升高,糖水消耗率上升,强迫游泳不动时间显著减少,脑组织病理损伤明显改善,血清、脑脊液5-HT显著升高,Glu显著降低,舌质和爪色RGB值升高,血液流变学各项指标均下降,血脂代谢相关指标均有所逆转。结论 通过“MCAO+CUMS”可成功构建具备“郁、瘀、痰”证素特点的病证结合动物模型,并建立相对应的客观评估标准。Objective To construct an animal model of post-stroke depression(PSD) based on the theory of “depression, stasis, phlegm”, with the aim of developing and validating an objective assessment system. Methods Rats were divided randomly into five groups: control, depression, stroke, PSD, and Baishile decoction groups. A PSD syndrome-based animal model was established in rats using a combination of middle cerebral artery occlusion(MCAO) and chronic unpredictable mild stress(CUMS). “Depression, stasis, phlegm” were then evaluated in the model rats using the Morris water maze, open field, forced swimming, and sucrose preference tests, and by detection of neurotransmitter levels, brain tissue pathology, tongue and forepaw color RGB values, and blood rheology. Results PSD rats exhibited significantly shorter target quadrant dwelling times, platform crossings, and climbing and rearing frequencies, a significantly lower sucrose preference, and a significantly higher immobility time in the forced swim test compared with control rats. Hematoxylin and eosin and Nissl staining revealed brain tissue damage in PSD rats. Serum and cerebrospinal fluid levels of 5-hydroxytryptamine(5-HT) were significantly decreased, glutamate levels were significantly increased, and tongue and forepaw RGB values were all decreased. Blood rheology showed a hypercoagulable state and blood lipid metabolism-related indicators were significantly abnormal. Rats in the Baishile decoction group showed significant improvements compared with the PSD group, including increased target quadrant dwelling times, number of platform crossings, and climbing and rearing frequencies, increased sucrose preference, decreased immobility time in the forced swim test, improved brain tissue pathology, increased serum and cerebrospinal fluid levels of 5-HT, decreased glutamate levels, increased tongue and claw RGB values, and varying degrees of improvement in blood rheology and blood lipid metabolism-related indicators. Conclusions The combination of MCAO and CUMS suc

关 键 词：卒中后抑郁 证素理论 病证结合模型 百事乐加味方 

分 类 号：Q95-33[生物学—动物学]