目的 利用斑馬魚模型評(píng)價(jià)安宮牛黃丸防治腦血管疾病的藥效。方法 辛伐他汀誘導(dǎo)斑馬魚腦出血模型，評(píng)價(jià)安宮牛黃丸腦出血保護(hù)作用；花生四烯酸誘導(dǎo)血栓模型，評(píng)價(jià)其血栓預(yù)防作用；辛伐他汀誘導(dǎo)微血管缺失模型，評(píng)價(jià)其促血管再生作用；用三氯化鋁誘導(dǎo)阿爾茨海默?。ˋD）模型，評(píng)價(jià)安宮牛黃丸對(duì)AD斑馬魚運(yùn)動(dòng)障礙恢復(fù)作用和反應(yīng)能力的改善作用。結(jié)果 與模型組比較，27.8、83.3和250 μg/mL安宮牛黃丸腦出血保護(hù)率分別為11%、41%和48%，83.3和250.0 μg/mL組腦出血發(fā)生率顯著降低（P<0.001）；與模型組比較，質(zhì)量濃度為333和1 000 μg/mL的安宮牛黃丸斑馬魚心臟紅細(xì)胞染色強(qiáng)度顯著增加（P<0.001），111、333和1 000 μg/mL組的血栓預(yù)防率分別為5%、33%和64%；質(zhì)量濃度為11.1、33.3和100.0 μg/mL的安宮牛黃丸斑馬魚腸下血管面積與模型組比較均顯著上升（P<0.001），其促血管再生率分別為21%、25%和26%；質(zhì)量濃度為111、333和1 000 μg/mL的安宮牛黃丸組斑馬魚運(yùn)動(dòng)速度與模型組比較均顯著提高（P<0.05、0.01），其運(yùn)動(dòng)障礙恢復(fù)率分別為48%、88%、78%；安宮牛黃丸111、333和1 000 μg/mL反應(yīng)能力改善率分別為15%、82%、75%，其中333和1 000 μg/mL組與模型組比較差異顯著（P<0.05、0.01）。結(jié)論 安宮牛黃丸能預(yù)防腦出血、預(yù)防血栓形成、重建血管微循環(huán)，對(duì)AD的運(yùn)動(dòng)功能障礙和反應(yīng)能力具有改善作用。

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.

浙江省科技重大專項(xiàng)（2014C03009）