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
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1. 湖南中医药大学科技创新中心,长沙 410208;2. 湖南省中医药研究院,长沙 410006;3. 湖南省脑科医院,长沙 410007

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Establishment of an animal model of cerebral small vessel disease with hypertension and aging as the main risk factors
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1. Science and Technology Innovation Center, Hunan University of Chinese Medicine, Changsha 410208, China. 2. Hunan Academy of Chinese Medicine, Changsha 410006. 3. Brain Hospital of Hunan Province, Changsha 410007

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    摘要:

    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。

    Abstract:

    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 noninvasive 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.

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刘彤彤,张熙,王枭冶,方锐,葛金文,孟盼.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[J].中国实验动物学报,2022,30(7):918~926.

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  • 收稿日期:2022-05-11
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  • 在线发布日期: 2023-03-10
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