[关键词]
[摘要]
目的 利用斑马鱼模型评价安宫牛黄丸防治脑血管疾病的药效。方法 辛伐他汀诱导斑马鱼脑出血模型,评价安宫牛黄丸脑出血保护作用;花生四烯酸诱导血栓模型,评价其血栓预防作用;辛伐他汀诱导微血管缺失模型,评价其促血管再生作用;用三氯化铝诱导阿尔茨海默病(AD)模型,评价安宫牛黄丸对AD斑马鱼运动障碍恢复作用和反应能力的改善作用。结果 与模型组比较,27.8、83.3和250 μg/mL安宫牛黄丸脑出血保护率分别为11%、41%和48%,83.3和250.0 μg/mL组脑出血发生率显著降低(P<0.001);与模型组比较,质量浓度为333和1 000 μg/mL的安宫牛黄丸斑马鱼心脏红细胞染色强度显著增加(P<0.001),111、333和1 000 μg/mL组的血栓预防率分别为5%、33%和64%;质量浓度为11.1、33.3和100.0 μg/mL的安宫牛黄丸斑马鱼肠下血管面积与模型组比较均显著上升(P<0.001),其促血管再生率分别为21%、25%和26%;质量浓度为111、333和1 000 μg/mL的安宫牛黄丸组斑马鱼运动速度与模型组比较均显著提高(P<0.05、0.01),其运动障碍恢复率分别为48%、88%、78%;安宫牛黄丸111、333和1 000 μg/mL反应能力改善率分别为15%、82%、75%,其中333和1 000 μg/mL组与模型组比较差异显著(P<0.05、0.01)。结论 安宫牛黄丸能预防脑出血、预防血栓形成、重建血管微循环,对AD的运动功能障碍和反应能力具有改善作用。
[Key word]
[Abstract]
Objective To investigate preventive and therapeutic effects of Angong Niuhuang Pills (ANP) on cerebrovascular diseases in Zebrafish models. Methods Zebrafish cerebral hemorrhage was induced by treatment with simvastatin, thrombosis by arachidonic acid, blood vessel loss by simvastatin, and Alzheimer's disease (AD) by AlCl3. Zebrafish models were treated with ANP by direct drug soaking at various concentrations. Results ANP had a significantly preventive effect on Zebrafish cerebral hemorrhage with an efficacy of 11%, 41%, and 48% at concentrations of 27.8, 83.3, and 250 μg/mL, respectively, and the incidence of cerebral hemorrhage in 83.3 and 250 g/mL groups decreased significantly compared with model group (P<0.001). Compared with model group, the red cell staining intensity of Zebrafish in 333 and 1 000 g/mL groups increased significantly (P<0.001), and the thrombus prevention rates of 111, 333, and 1000 g/mL groups were 5%, 33%, and 64% respectively. Compared with model group, the intestinal vascular area of Zebrafish in ANP 11.1, 33.3, and 100.0 μg/mL groups increased significantly (P<0.001), and the rate of angiogenesis was 21%, 25% and 26% respectively. ANP promoted dyskinesia recovery by 48%, 88%, and 78%, and improved response efficiency by 15%, 82% and 75%, respectively in AD zebrafish at concentrations of 111, 333, and 1000 μg/mL. Conclusions Our results in this study support ANP as a preventive and therapeutic medicine for cerebral hemorrhage, cerebral ischemia, thrombosis and AD.
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[基金项目]
浙江省科技重大专项(2014C03009)