柚皮苷及柚皮素对高脂模型大鼠单核细胞过氧化物酶体增殖物激活受体-δ水平的影响

中国临床药理学与治疗学 ›› 2013, Vol. 18 ›› Issue (1): 6-10.

柚皮苷及柚皮素对高脂模型大鼠单核细胞过氧化物酶体增殖物激活受体-δ水平的影响

杨颖^1,2, 袁斌², 周春阳², 程龙献¹

¹华中科技大学协和医院心内科华中科技大学同济医院心务管病研究所,武汉 430022, 湖北;
²川北医学院药物研究所, 南充 637000,四川

收稿日期:2012-12-15 修回日期:2012-12-15 发布日期:2013-02-05
通讯作者: 周春阳,男,教授,硕士生导师,研究方向:心血管药理。E-mail: chunyangzhou@hotmail.com
作者简介:杨颖,博士,研究方向:心血管治疗学。 Tel: 13720229937 E-mail: 1842415202@qq.com;程龙献,男,教授,博士生导师,研究方向:心血管药理。E-mail: chenglongxian@sina.com
基金资助:
四川省教育厅科学研究项目(1026047)

Effects of naringin and naringenin on the level of peroxisome proliferator-activated receptors δ in monocyte of diet-induced obese rats

YANG Ying^1,2, YUAN Bin², ZHOU Chun-yang², CHENG Long-xian¹

¹Department of Cardiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, Hubei, China;
²Institute of Materia Medica, North Sichuan Medical College, Nanchong 637000, Sichuan,China

Received:2012-12-15 Revised:2012-12-15 Published:2013-02-05

摘要/Abstract

摘要： 目的: 探讨黄酮类化合物柚皮苷及柚皮素对高脂模型大鼠单核细胞过氧化物酶体增殖物激活受体-δ(Peroxisome proliferator-activated receptors δ,PPAR-δ)水平的影响。方法: 实验动物分为普通饲料组、高脂饲料对照组、柚皮苷和柚皮素高剂量及低剂量组。除普通饲料组外,其余各组通过高脂乳剂灌胃,建立高脂模型。然后再分别给予 0.5%的羧甲基纤维素(CMC)或不同剂量的柚皮素或柚皮苷灌胃8周。实验结束后应用RT-PCR法检测外周血单核细胞PPAR-δ的表达,测定血中甘油三脂(TG)、总胆固醇(TC)、高密度脂蛋白胆固醇(HDL-C)、低密度脂蛋白胆固醇(LDL-C)及极低密度脂蛋白胆固醇的水平。结果: 与高脂饲料对照组相比,高剂量柚皮苷和柚皮素组血中甘油三脂、总胆固醇、低密度脂蛋白胆固醇及极低密度脂蛋白胆固醇(VLDL-C)的水平降低,差异有统计学意义(P均<0.01 );HDL-C水平明显升高(P<0.01);高剂量柚皮素及柚皮苷组外周血单核细胞PPAR-δ mRNA的表达高于高脂饲料对照组,差异有统计学意义(均P<0.05);相关性分析结果表明PPAR-δ与甘油三脂(r=0.158, P<0.05)、总胆固醇水平(r=0.147, P<0.05)呈正相关。结论: 高剂量的柚皮苷与柚皮素可降低血脂水平,上调PPAR-δ的表达。

关键词: 柚皮苷, 柚皮素, 高脂, 过氧化物酶体增殖物激活受体-δ

Abstract: AIM: To study the effects of naringin and naringenin on the expression of peroxisome proliferator-activated receptors δ(PPAR-δ) in peripheral blood monocyte of diet-induced obese rats. METHODS: The experimental animals were divided into normal diet control group, high-fat diet control group and high-fat diet groups treated with high or low dose of naringin and naringenin, respectively.After treated by high lipid emulsion garage except for normal diet control group, the high-fat diet rat models were established successfully.Then, vehicle (0.5%CMC) or different dosages of naringin or naringenin had been given to the rats for 8 weeks.The PPAR-δ mRNA expression was detected by reverse transcription polymerase chain reaction ( RT-PCR) , the serum levels of triglyceride, total cholesterol, high density lipoprotein-cholesterol,low density lipoprotein-cholesterol and very low density lipoprotein-cholesterol were measured respectively.RESULTS: Compared with the high-fat diet control group,the levels of triglyceride, total cholesterol, low density lipoprotein-cholesterol and very low density lipoprotein-cholesterol were decreased in high dose of naringin and naringenin groups(all P<0.01);the level of high density lipoprotein-cholesterol was increased(P<0.01);the expression of PPAR-δ mRNA in peripheral blood monocyte in high dose of naringin and naringenin groups was increased (P<0.05).The positive correlation between PPAR-δ(r=0.158, P<0.05) and triglyceride, total cholestero(r=0.147, P<0.05) were observed through correlation analysis. CONCLUSION: The high dosages of naringin and naringenin might reduce the levels of serum lipid and increase the expression of PPAR-δ in peripheral blood monocyte.

Key words: Naringin, Naringenin, Hyperlipidemia, Peroxisome proliferator-activated receptors δ

中图分类号:

R965.2

杨颖, 袁斌, 周春阳, 程龙献. 柚皮苷及柚皮素对高脂模型大鼠单核细胞过氧化物酶体增殖物激活受体-δ水平的影响[J]. 中国临床药理学与治疗学, 2013, 18(1): 6-10.

YANG Ying, YUAN Bin, ZHOU Chun-yang, CHENG Long-xian. Effects of naringin and naringenin on the level of peroxisome proliferator-activated receptors δ in monocyte of diet-induced obese rats[J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2013, 18(1): 6-10.

参考文献

[1] PU P, Gao DM, Mohamed S, et al.Naringin ameliorates metabolic syndrome by activating amp-activated protein kinase in mice fed a high-fat diet[J].Arch Biochem Biophys,2012,518(1):61-70.
[2] Bodas R, Prieto N, Jordan MJ, et al.The liver antioxidant status of fattening lambs is improved by naringin dietary supplementation at 0.15% rates but not meat quality[J].Animal,2012,6(5):863-870.
[3] Filip-Ciubotaru F, Manciuc C, Grigore C,et al.ppars: physiological functions and pharmacological roles of agonists in human diseases. Note ii[J].Rev Med Chir Soc Med Nat Iasi,2012,116(1):240-247.
[4] Ooi EM, Watts GF, Sprecher DL, et al.Mechanism of action of a peroxisome prolifertor-activated receptor(ppar)-delta agonist on lipoprotein metabolism in dyslipidemic subjects with central obesity[J]. J Clin Endocrinol Metab,2011,96(10):1568-1576.
[5] Jung UJ, Lee MK,Park YB, et al.Effect of citrus flavonoids on lipid metabolism and glucose-regulating enzyme mma levels in type-2 diabetic mice[J]. Int J Biochem Cell Biol,2006,38(7):1134-1145.
[6] Little TJ, Feinle-Bisset C.Effects of dietary fat on appetite and energy intake in health and obesity-oral and gastrointestinal sensory contributions[J]. Physiol Behav,2011,104(4):613-620.
[7] Biagiotti E, Guidi L, Del Grande P, et al.Glucose-6-phosphate dehydrogenase expression associated with nadph-dependent reactions in cerebellar neurons[J]. Cerebellum, 2003,2(3):178-183.
[8] Xulu S, Oroma Owira PM.Naringin ameliorates atherogenic dyslipidemia but not hyperglycemia in rats with type 1 diabetes[J]. J Cardiovasc Pharmacol,2012,59(2):133-141.
[9] Lin Y, Vermeer MA, Bos W, et al.Molecular structures of citrus flavonoids determine their effects on lipid metabolism in HEPG2 cells by primarily suppressing apob secretion[J]. J Agric Food Chem, 2011,59(9):4496-4503.
[10] Sharma AK, Bharti S, Ojha S, et al.Up-regulation of ppargamma, heat shock protein-27 and -72 by naringin attenuates insulin resistance, beta-cell dysfunction, hepatic steatosis and kidney damage in a rat model of type 2 diabetes[J]. Br J Nutr,2011,106(11):1713-1723.
[11] Oliver WR Jr, Shenk JL, Snaith MR, et al.A selective peroxisome proliferator-activated receptor delta agonist promotes reverse cholesterol transport[J].Proc Natl Acad Sci USA, 2001,98(9):5306-5311.
[12] Briand F, Naik SU, Fuki I, et al.Both the peroxisome proliferator-activated receptor delta agonist, gw0742, and ezetimibe promote reverse cholesterol transport in mice by reducing intestinal reabsorption of hdl-derived cholesterol[J]. Clin Transl Sci,2009, 2(2):127-133.
[13] Morikawa K, Nonaka M, Mochizuki H, et al.Naringenin and hesperetin induce growth arrest, apoptosis, and cytoplasmic fat deposit in human preadipocytes[J]. J Agric Food Chem,2008,56(22):11030-11037.

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