斑马鱼平台研究七种中药单体的降脂作用
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摘要
本研究利用斑马鱼平台研究七种中药单体的降脂作用。通过高脂饮食构建斑马鱼高脂血症模型,使用油红O染色研究七种中药单体对斑马鱼血脂的影响,通过检测斑马鱼血清总胆固醇、甘油三酯验证药物的降脂作用,并初步探讨药物降脂可能的机制。结果显示,高脂饮食后斑马鱼幼鱼血脂升高,经七种中药单体处理后,油红O染色显示大黄酚能降低斑马鱼幼鱼血脂。高脂饮食的成年斑马鱼经大黄酚药浴8周后血清总胆固醇、甘油三酯水平均下降。大黄酚增加斑马鱼肠蠕动的频率,加速肠道排空。上述结果表明大黄酚可降低高脂饮食后斑马鱼的血脂水平,其机制可能是大黄酚加快了高脂食物从肠道排出,减少了肠道对脂质的吸收。
The present study aimed to study lipid-lowering effect of seven traditional Chinese medicine monomers in zebrafish system. Zebrafish were fed with high fat diet to establish a hyperlipemia model, then fasted and bathed with seven traditional Chinese medicine monomers stigmasterol, triacontanol, chrysophanol, vanillic acid, shikimic acid, polydatin and oleanolic acid respectively. The oil red O staining was used to detect the blood lipids of zebrafish. Serum total cholesterol and triglyceride levels were detected to validate the lipid-lowering effect. The result showed that a zebrafish model of hyperlipemia could be established by feeding larvae zebrafish with high fat diet. Among the seven traditional Chinese medicine monomers, chrysophanol had lipid-lowering effect. Chrysophanol significantly reduced serum total cholesterol and triglyceride levels in adult zebrafish fed with high fat diet. Chrysophanol accelerated peristalsis frequency of zebrafish intestine and the excretion of high fat food. It is concluded that chrysophanol has lipidlowering effect in zebrafish, and the mechanism of the effect may be due to the roles of chrysophanol in reducing lipid absorption from gastrointestinal tract and accelerating the excretion of food.
The present study aimed to study lipid-lowering effect of seven traditional Chinese medicine monomers in zebrafish system. Zebrafish were fed with high fat diet to establish a hyperlipemia model, then fasted and bathed with seven traditional Chinese medicine monomers stigmasterol, triacontanol, chrysophanol, vanillic acid, shikimic acid, polydatin and oleanolic acid respectively. The oil red O staining was used to detect the blood lipids of zebrafish. Serum total cholesterol and triglyceride levels were detected to validate the lipid-lowering effect. The result showed that a zebrafish model of hyperlipemia could be established by feeding larvae zebrafish with high fat diet. Among the seven traditional Chinese medicine monomers, chrysophanol had lipid-lowering effect. Chrysophanol significantly reduced serum total cholesterol and triglyceride levels in adult zebrafish fed with high fat diet. Chrysophanol accelerated peristalsis frequency of zebrafish intestine and the excretion of high fat food. It is concluded that chrysophanol has lipidlowering effect in zebrafish, and the mechanism of the effect may be due to the roles of chrysophanol in reducing lipid absorption from gastrointestinal tract and accelerating the excretion of food.
引文
1 Pahan K.Lipid-lowering drugs.Cell Mol Life Sci 2006;63(10):1165-1178.
2 Holtta-Vuori M,Salo V,Nyberg L,Brackmann C,Enejder A,Panula P,Ikonen E.Zebrafish:gaining popularity in lipid research.Biochem J 2010;429:235-242.
3 Wiart C.A note on the relevance of chrysophanol to food and anticancer research.Mol Nutr Food Res 2012;56(6):843.
4 Ni CH,Chen PY,Lu HF,Yang JS,Huang HY,Wu SH,Ip SW,Wu CT,Chiang SY,Lin JG,Wood WG,Chung JG.Chrysophanol-induced necrotic-like cell death through an impaired mitochondrial ATP synthesis in Hep3B human liver cancer cells.Arch Pharm Res 2012;35(5):887-895.
5 Lu CC,Yang JS,Huang AC,Hsia TC,Chou ST,Kuo CL,Lu HF,Lee TH,Wood WG,Chung JG.Chrysophanol induces necrosis through the production of ROS and alteration of ATP levels in J5 human liver cancer cells.Mol Nutr Food Res 2010;54(7):967-976.
6 Chen K,Wang CQ,Fan YQ,Xie YS,Yin ZF,Xu ZJ,Zhang HL,Cao JT,Wang Y.Application of chrysophanol in zebrafish to reduce dietary introduced lipid and its possible mechanism.Int J Clin Exp Med 2015;8(7):10558-10567.
7 Burns CG,Milan DJ,Grande EJ,Rottbauer W,Mac Rae CA,Fishman MC.High-throughput assay for small molecules that modulate zebrafish embryonic heart rate.Nat Chem Biol2005;1:263-264.
8 Pattone E,Widlund HR,Kutok JL,Kopani KR,Amatruda JF,Murphey RD,Berghmans S,Mayhall EA,Traver D,Fletcher CD,Aster JC,Granter SR,Look AT,Lee C,Fisher DE,Zon LI.BRAF mutations are sufficient to promotenevi formation and cooperate with p53 in the genesis of melanoma.Curr Biol 2005;15(3):249-254.
9 Baxendale S,Holdsworth CJ,Meza SL,Harrison MR,Fox J,Parkin CA,Ingham PW,Cunliffe VT.Identification of compounds with anti-convulsant properties in a zebrafish model of epileptic seizures.Dis Model Mech 2012;5(6):773-784.
10 Peterson RT,Fishman MC.Designing zebrafish chemical screens.Methods Cell Biol 2011;105:525-541.
2 Holtta-Vuori M,Salo V,Nyberg L,Brackmann C,Enejder A,Panula P,Ikonen E.Zebrafish:gaining popularity in lipid research.Biochem J 2010;429:235-242.
3 Wiart C.A note on the relevance of chrysophanol to food and anticancer research.Mol Nutr Food Res 2012;56(6):843.
4 Ni CH,Chen PY,Lu HF,Yang JS,Huang HY,Wu SH,Ip SW,Wu CT,Chiang SY,Lin JG,Wood WG,Chung JG.Chrysophanol-induced necrotic-like cell death through an impaired mitochondrial ATP synthesis in Hep3B human liver cancer cells.Arch Pharm Res 2012;35(5):887-895.
5 Lu CC,Yang JS,Huang AC,Hsia TC,Chou ST,Kuo CL,Lu HF,Lee TH,Wood WG,Chung JG.Chrysophanol induces necrosis through the production of ROS and alteration of ATP levels in J5 human liver cancer cells.Mol Nutr Food Res 2010;54(7):967-976.
6 Chen K,Wang CQ,Fan YQ,Xie YS,Yin ZF,Xu ZJ,Zhang HL,Cao JT,Wang Y.Application of chrysophanol in zebrafish to reduce dietary introduced lipid and its possible mechanism.Int J Clin Exp Med 2015;8(7):10558-10567.
7 Burns CG,Milan DJ,Grande EJ,Rottbauer W,Mac Rae CA,Fishman MC.High-throughput assay for small molecules that modulate zebrafish embryonic heart rate.Nat Chem Biol2005;1:263-264.
8 Pattone E,Widlund HR,Kutok JL,Kopani KR,Amatruda JF,Murphey RD,Berghmans S,Mayhall EA,Traver D,Fletcher CD,Aster JC,Granter SR,Look AT,Lee C,Fisher DE,Zon LI.BRAF mutations are sufficient to promotenevi formation and cooperate with p53 in the genesis of melanoma.Curr Biol 2005;15(3):249-254.
9 Baxendale S,Holdsworth CJ,Meza SL,Harrison MR,Fox J,Parkin CA,Ingham PW,Cunliffe VT.Identification of compounds with anti-convulsant properties in a zebrafish model of epileptic seizures.Dis Model Mech 2012;5(6):773-784.
10 Peterson RT,Fishman MC.Designing zebrafish chemical screens.Methods Cell Biol 2011;105:525-541.