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丹龙醒脑方对血管性痴呆肾虚血瘀证大鼠认知及海马病理的影响OA

Effect of Danlong Xingnao Formula on Cognitive and Hippocampal Pathology of Vascular Dementia Rats with Kidney Deficiency and Blood Stasis Syndrome

中文摘要英文摘要

目的:建立肾虚血瘀证血管性痴呆(VD)病证结合动物模型,观察丹龙醒脑方对其认知功能及海马病理的影响.方法:72只SD大鼠随机分为假手术组12只和模型组60只.模型组60只采用高脂饮食喂养结合改良2-VO法及摘除性器官法建立VD的肾虚血瘀证大鼠模型,造模成功后随机分为模型组、尼莫地平组和丹龙醒脑方高、中、低剂量组,给予不同剂量丹龙醒脑方和尼莫地平干预4周.观察假手术组和模型组大鼠表征,检测雌二醇(E2)、睾酮(T)、骨钙素(OCN)、钙(Ca)、内皮素-1(ET-1)、一氧化氮(NO)和血液流变学等指标变化,通过Morris水迷宫实验进行行为学检测;取全脑进行海马区HE染色.结果:建模成功大鼠可见典型VD的肾虚血瘀证模型表征,E2、T、OCN、Ca和NO水平明显低于假手术组,全血黏度(低、中、高切)和ET-1水平明显高于假手术组,逃避潜伏期较假手术组明显延长、穿越平台次数及目标象限停留时间较假手术组明显缩短(P<0.01).与模型组比较,丹龙醒脑方各剂量组、尼莫地平组逃避潜伏期显著缩短、穿越平台次数及目标象限停留时间显著延长(P<0.05,P<0.01),丹龙醒脑方各剂量组、尼莫地平组大鼠海马CA1区病理状态有所改善.结论:高脂饮食喂养结合改良2-VO法及摘除性器官法构建的模型大鼠符合VD肾虚血瘀病证结合特点.丹龙醒脑方可以提高VD肾虚血瘀证大鼠的认知能力,并改善其海马病理形态,发挥改善VD肾虚血瘀证的作用.

Objective:To establish the animal model of vascular dementia(VD)disease with kidney deficiency and blood stasis syndrome,and observe the effects of Danlong Xingnao Formula(DXF)on cognitive function and hippocampal pathology of the animal model.Methods:Seventy-two SD rats were randomly divided into sham operation group(n=12)and model group(n=60).In the model group,60 rats were fed with high-fat diet combined with modified 2-VO method and sexual organ removal method to establish the model of VD with kidney deficiency and blood stasis syndrome.After successful modeling,the rats were randomly divided into model group,nimodipine group and DXF high-dose,medium-dose and low-dose groups,and the animals were administered for 4 weeks.The changes of estradiol(E2),testosterone(T),osteocalcin(OCN),calcium(Ca),hemorheology,endothelin-1(ET-1),nitric oxide(NO)and other indexes were observed in the sham operation group and model group.Behavioral testing was conducted using the Morris water maze experiment.HE staining was conducted for the hippocampus of the brain.Results:Characteristics of kidney deficiency and blood stasis syndrome model with typical VD were visible in the successful modeling rats.In the model group,the levels of E2,T,OCN,Ca and NO were significantly lower than those in the sham group,while the whole blood viscosity(low,medium and high shear)and ET-1 level were significantly higher than those in the sham group,the escape latency was significantly longer than that of the sham group,and the number of crossing platforms and the target quadrant residence time were significantly shorter than those of the sham group(P<0.01).Compared with the model group,the DXF groups and nimodipine group had significantly shorter escape latency and longer crossing platforms and target quadrant residence time(P<0.05,P<0.01).The pathological status of the hippocampal CA1 area in rats treated with various doses of DXF and nimodipine improved.Conclusion:The model rats constructed by combining high-fat diet feeding with improved 2-VO and genital organ removal method met the characteristics of VD with kidney deficiency and blood stasis syndrome.Danlong Xingnao Formula can improve the cognitive ability of rats with VD and kidney deficiency and blood stasis syndrome,improve the pathological morphology of the hippocampus,and play a role in improving VD with kidney deficiency and blood stasis syndrome.

张运辉;杨梦琳;周小青;伍大华;刘霞;杨昆;吴巧

重庆三峡医药高等专科学校,重庆 404120湖南中医药大学,湖南 长沙 410208湖南中医药大学,湖南 长沙 410208||湖南省中医药研究院附属医院,湖南 长沙 410006

丹龙醒脑方血管性痴呆认知功能海马肾虚血瘀证

Danlong Xingnao FormulaVascular dementiaCognitive functionHippocampusKidney deficiency and blood stasis syndrome

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国家自然科学基金项目(81874462);重庆市教委科学技术研究计划项目(KJQN202302708);重庆市中医药传承创新团队;重庆市教育委员会科学技术研究项目(KJQN202102702);重庆市级乡村振兴对口帮扶科技项目(2023TIAD-ZXX0010);重庆市教委科学技术项目(KJQN201802710)

10.19656/j.cnki.1002-2406.20240405

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