高血压和衰老为主要危险因素的脑小血管病动物模型的建立

Establishment of an animal model of cerebral small vessel disease with hypertension and aging as the main risk factors

目的以SHR大鼠为研究对象,采用不同时间的D-半乳糖诱导的方法构建以高血压和衰老为主要危险因素的脑小血管病动物模型。方法18只SHR大鼠按体重随机分为3组:D-半乳糖150 mg/(kg·d)+4周组、D-半乳糖150 mg/(kg·d)+8周组、D-半乳糖150 mg/(kg·d)+12周组,每组6只。另设6只WKY大鼠为空白对照组。造模期间,每周采用无创血压计监测大鼠血压变化;造模结束后,采用Morris水迷宫检测大鼠认知功能变化;称重法检测大鼠脑指数、胸腺指数、脾指数和肝指数;ELISA法检测大鼠血清中T-SOD、GSH-Px、MDA、NEFL含量和CALB/SALB指数;HE和LFB染色观察大鼠脑组织前额叶皮质细胞形态、脑室微出血以及胼胝体髓鞘损伤情况。结果与WKY组比较,随着D-半乳糖注射时间的增加,各组SHR大鼠血压升高;学习记忆能力明显下降;脑、胸腺、脾、肝各脏器指数降低;血清中T-SOD、GSH-Px含量减少,MDA、NEFL水平和CALB/SALB指数上升;脑组织前额叶皮质细胞病变数量增多,血管周围间隙和三脑室背侧微出血量增大以及胼胝体髓鞘空泡化加重。其中以D-半乳糖150 mg/(kg·d)注射12周组大鼠的病理生理变化最显著。结论SHR大鼠注射D-半乳糖150 mg/(kg·d)12周可复制与人类CSVD疾病状态接近的CSVD动物模型。

Objective Establish an animal model of small cerebral vascular disease(CVD)in SHR rats induced by D-galactose at various times.Methods Eighteen SHR rats were randomly divided into three groups according to body weight:D-galactose 150 mg/(kg·d)+4 week,D-galactose 150 mg/(kg·d)+8 week,and D-galactose 150 mg/(kg·d)+12 week groups with six rats in each group.Another 6 WKY rats were used as the blank control group.A non-invasive sphygmomanometer was used to monitor blood pressure of rats every week during modeling.The Morris water maze was used to assess the cognitive function of rats after modeling.Brain,thymus,spleen,and liver indexes were measured by the weighing method.T-SOD,GSH-Px,MDA,NEFL and CALB/SALB contents in rat serum were determined by ELISA.HE and LFB staining were used to observe cell morphology of the prefrontal cortex,ventricular microhemorrhage,and myelin sheath injury of the corpus callosum.Results Compared with the WKY group,the blood pressure of SHR rats was increased with the increase in D-galactose injection time.Learning and memory abilities were decreased significantly.Brain,thymus,spleen,and liver indexes were decreased.T-SOD and GSH-Px contents in serum were decreased,while MDA and NEFL,and CALB/SALB levels were increased.The number of cytopathic lesions in the prefrontal cortex was increased,the amount of perivascular space and dorsal microbleeding of the third ventricle were increased,and vacuolization of the myelin sheath of the corpus callosum was increased.The most significant pathophysiological changes were observed in rats treated with 150 mg/(kg·d)D-galactose for 12 weeks.Conclusions SHR rats injected with 150 mg/(kg·d)D-galactose for 12 weeks are a CSVD animal model similar to the human CSVD disease status.