基于斑马鱼模型的水溶性姜黄素制剂抗血栓和抗炎活性研究

Study on antithrombotic and anti-inflammatory activities of water-soluble curcumin based on zebrafish model

目的基于斑马鱼模型探究水溶性姜黄素制剂对血栓形成和炎症消退的作用。方法随机挑选受精后3 d的斑马鱼分为对照组、模型组、阳性药对照组、水溶性姜黄素制剂(姜黄素质量分数为10%,125、250、500、1000、2000μg·mL^(−1))组、普通姜黄素(姜黄素质量分数为95%,125、250、500、1000、2000μg·mL^(−1))组,每组30尾。除对照组外,其余组使用花生四烯酸、脂多糖、五水合硫酸铜分别诱导建立血栓、细菌性炎症和神经性炎症模型。通过观察分析斑马鱼红细胞染色强度和炎症部位中性粒细胞个数来评价水溶性姜黄素制剂抑制血栓形成和抗炎作用。结果与对照组比较,模型组斑马鱼心脏红细胞染色强度明显减少(P<0.001)、炎症部位中性粒细胞个数明显增多(P<0.001);与模型组比较,水溶性姜黄素制剂≥250μg·mL^(−1)质量浓度时能显著抑制血栓形成、消退炎症,主要表现为斑马鱼心脏红细胞染色强度显著升高(P<0.001)、炎症部位中性粒细胞个数明显减少(P<0.05、0.01、0.001);姜黄素在≥1000μg·mL^(−1)时能显著抑制血栓形成(P<0.01、0.001),≥500μg·mL^(−1)时能显著消退炎症(P<0.05、0.01、0.001)。姜黄素为水溶性姜黄素制剂给药浓度2~8倍的条件下,才能达到相同的抑制血栓和炎症形成的效果。结论与普通姜黄素组比较,在相同给药浓度下,水溶性姜黄素制剂具有更好的抑制血栓形成和抗炎作用。

Objective To explore the effect of water-soluble curcumin on thrombosis and inflammation regression based on zebrafish model.Method Zebrafish three days after fertilization were randomly selected to be divided into control group,model control group,positive drug control group,water-soluble curcumin with different concentrations experimental(curcumin mass fraction 10%,125,250,500,1000 and 2000μg·mL^(−1))groups and ordinary curcumin with different concentrations experimental(turmeric mass fraction 95%,125,250,500,1000 and 2000μg·mL^(−1))groups.Each group has 30 zebrafish.Except for the normal control group,the other experimental groups used Arachidonic acid,Lipopolysaccharide and CuSO_(4)·5H_(2)O to induce thrombosis,bacterial inflammation and neurological inflammation,respectively.By observing and analyzing the staining intensity of red blood cells and the number of neutrophils in the inflammation sites of zebrafish,the antithrombotic and anti-inflammatory effects of water-soluble curcumin were evaluated.Results Compared with the control group,the erythrocyte staining intensity of zebrafish heart in model control group was significantly decreased(P<0.001),and the number of neutrophils in the inflammation site was significantly increased(P<0.001).Compared with model group,water-soluble curcumin at 250μg·mL^(−1) could significantly inhibit thrombosis and subside inflammation,which were mainly represented by increased erythrocyte staining intensity of zebrafish heart(P<0.001)and decreased neutrophil number at the inflammation site(P<0.05,0.01,0.001).When curcumin at≥1000μg·mL^(−1),it can significantly inhibit thrombosis(P<0.01,0.001),when≥500μg·mL^(−1),it can significantly reduce inflammation(P<0.05,0.01,0.001).Curcumin can achieve the same inhibitory effect on thrombosis and inflammation only when administered at a concentration of 2-8 times that of water-soluble curcumin preparations.Conclusion Compared with the experimental groups of ordinary curcumin,the water-soluble curcumin showed better antithrombotic and anti-inflammatory effects at the same concentration.