A rat model of vascular dementia for evaluating Chinese medicine prescriptions

Shi-Jun Yang; Chen Chen; Cheng-Zhe Zu; Run-Mei Yang; Cheng-Cheng Wang; Fei-Fei Pu; Qiu-Ting Wang; Xiao-Ya Li; Xin Zhao; Da-Yong Cai

doi:10.1007/s11655-015-2435-4

A rat model of vascular dementia for evaluating Chinese medicine prescriptions

Chin J Integr Med. 2016 Mar 8. doi: 10.1007/s11655-015-2435-4. Online ahead of print.

Authors

Affiliations

¹ Institute of Medicinal Plant Development, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, 100193, China.
² Institute of Medicinal Plant Development, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, 100193, China. dycai@implad.ac.cn.

PMID: 26956462
DOI: 10.1007/s11655-015-2435-4

Abstract

Objective: To develop a new model of vascular dementia for evaluating Chinese medicine prescriptions.

Methods: Eighty-eight male Wistar rats were randomly divided into 4 groups. At d₀₀, d₄₂, d₇₀, d₉₈ (n_i=20, 20, 24, 24) during fatty-feeding, rats in each group were further divided into 10 or 12 subgroups (n_i=2), respectively. Lacunar stroke were replicated with the injection of thrombi which coagulated artificially from itself blood. The median lethal doses (LD₅₀) were regressed from accumulative mortality in each geometric thrombus doses (k=0.75, 0.5, 0.85, 0.85), respectively. The degree of vascular dementia was evaluated as exploratory, learning and memorizing abilities. The median effective dose of thrombus for replicating rat model was regressed from dementia scores which were derived from the abilities. The linear correlation was regressed between the values of LD₅₀ or effective dose (ED₅₀) and the durations (days) of hypercholesterolemia. This model of vascular dementia was pathologically confirmed as the neural injuries from lacunar stroke in rats.

Results: The hypercholesterolemia was indicated as elevated total cholesterol, triglyeerides low-density lipoprotein cholesterol, and decreased high-density lipoprotein cholesterol. The values of LD5₀ with its 95% confidence intervals (CI) were 1525.0 (1361.0-1709.0), 584.3 (490.1-696.6), 168.7 (163.7-173.8), or 62.4 (59.5-65.4) mg/mL, at d₀₀, d₄₂, d₇₀, and d₉₈, respectively. There is a linear regression between the values of LD₅₀ and the durations of hypercholesterolemia (y=-15.33x+1390.0, r=0.963, P<0.05). The values of ED₅₀ with its 95% CI were 528.8 (340.5-821.4), 217.0 (20.84-2259.0), 96.3 (23.4-402.6), or 47.0 (43.7-50.6) mg/mL from dementia score, at d₀₀, d₄₂, d₇₀, and d₉₈, respectively. There is a linear regression between the values of ED₅₀ and the durations of hypercholesterolemia (y=-4.992x+484.2, r=0.965, P<0.05). The neural injuries were demonstrated as neural degeneration and necrosis.

Conclusions: For evaluating Chinese medicine, a model of vascular dementia in rats is set up with the lacunar stroke from self-thrombosis during hypercholesterolemia. This model from lacunar stroke is useful to investigate the pathogenesis and treatment of vascular dementia.

Keywords: Chinese medicine prescription; hypercholesterolemia; lacunar stroke; rat model; vascular dementia.