甘草酸差向异构体不同配比对酒精性肝损伤脂质代谢的影响

doi:10.3969/j.issn.1000-1565.2018.01.007

摘要/Abstract

摘要： 研究18α-甘草酸和18β-甘草酸不同配比对酒精性肝损伤脂质代谢的影响,筛选最佳配比,为临床合理用药提供依据.大鼠随机分为正常组、酒精性肝损伤组、水飞蓟宾阳性组、甘草酸给药1~7组(18α-甘草酸和18β-甘草酸体积比依次为10∶0,8∶2,6∶4,5∶5,4∶6,2∶8,0∶10),造模4周后,麻醉处死.检测脂质代谢指标血清和肝脏中的甘油三酯(TG)、胆固醇(TC)、高密度脂蛋白(HDL)、低密度脂蛋白(LDL)和粪便中的TC,TG;氧化应激指标超氧化物歧化酶(SOD),谷胱甘肽(GSH),丙二醛(MDA);进行HE染色以及油红O染色.与模型组相比,给药组的TC,TG,HDL及LDL水平均有显著性变化,其中给药5组的效果最佳.甘草酸对于酒精性肝损伤的脂质代谢有较好的治疗作用,18α-甘草酸和18β-甘草酸最佳体积配比为4∶6.

关键词: 18α-甘草酸, 18β-甘草酸, 不同配比, 酒精性肝损伤, 脂质代谢

Abstract: To investigate the effect of different proportions of 18α,β-glycyrrhizic acids on lipid metabolism on alcoholic liver injury and screen out their optimal combination proportion, the rats were randomly divided into ten groups: normal control group, model control group, siibin group and glycyrrhizic treatment group 1-7(α∶β=10∶0,8∶2,6∶4,5∶5,4∶6,2∶8,0∶10).After 4 weeks, the rats were sacrificed.The serum and hepatic TC, TG, HDL and LDL levels and fecal TC and TG levels were measured.And liver was stained with oil red O.We investigated the effect of different proportions of 18α,β-glycyrrhizic acid on lipid metabolism on alcoholic liver injury and further screen out optimal combination proportion.The TC, TG, HDL and LDL levels were significant different among different glycyrrhizic treatment group, and the glycyrrhizic treatment group 5 is the optimal combination proportion.Our results show that glycyrrhizic treatment could modulate lipid metabolism on alcoholic liver injury, and the- DOI:10.3969/j.issn.1000-1565.2018.01.007甘草酸差向异构体不同配比对酒精性肝损伤脂质代谢的影响杨飒,孙晓可,孟祥波,周程艳,赵燕燕(河北大学药学院,河北省药物质量分析控制重点实验室,河北保定 071002)摘要:研究18α-甘草酸和18β-甘草酸不同配比对酒精性肝损伤脂质代谢的影响,筛选最佳配比,为临床合理用药提供依据.大鼠随机分为正常组、酒精性肝损伤组、水飞蓟宾阳性组、甘草酸给药1~7组(18α-甘草酸和18β-甘草酸体积比依次为10∶0,8∶2,6∶4,5∶5,4∶6,2∶8,0∶10),造模4周后,麻醉处死.检测脂质代谢指标血清和肝脏中的甘油三酯(TG)、胆固醇(TC)、高密度脂蛋白(HDL)、低密度脂蛋白(LDL)和粪便中的TC,TG;氧化应激指标超氧化物歧化酶(SOD),谷胱甘肽(GSH),丙二醛(MDA);进行HE染色以及油红O染色.与模型组相比,给药组的TC,TG,HDL及LDL水平均有显著性变化,其中给药5组的效果最佳.甘草酸对于酒精性肝损伤的脂质代谢有较好的治疗作用,18α-甘草酸和18β-甘草酸最佳体积配比为4∶6.关键词:18α-甘草酸;18β-甘草酸;不同配比;酒精性肝损伤;脂质代谢中图分类号:R285.5 文献标志码:A 文章编号:1000-1565(2018)01-0041-08Effects of different proportions of 18α,β-glycyrrhizic acids on lipidmetabolism on alcoholic liver injuryYANG Sa, SUN Xiaoke, MENG Xiangbo, ZHOU Chengyan, ZHAO Yanyan(Key Laboratory of Pharmaceutical Quality Control of Hebei ProvinceCollege of Pharmaceutical Sciences, Hebei University, Baoding 071002, China)Abstract: To investigate the effect of different proportions of 18α,β-glycyrrhizic acids on lipid metabolism on alcoholic liver injury and screen out their optimal combination proportion, the rats were randomly divided into ten groups: normal control group, model control group, siibin group and glycyrrhizic treatment group 1-7(α∶β=10∶0,8∶2,6∶4,5∶5,4∶6,2∶8,0∶10).After 4 weeks, the rats were sacrificed.The serum and hepatic TC, TG, HDL and LDL levels and fecal TC and TG levels were measured.And liver was stained with oil red O.We investigated the effect of different proportions of 18α,β-glycyrrhizic acid on lipid metabolism on alcoholic liver injury and further screen out optimal combination proportion.The TC, TG, HDL and LDL levels were significant different among different glycyrrhizic treatment group, and the glycyrrhizic treatment group 5 is the optimal combination proportion.Our results show that glycyrrhizic treatment could modulate lipid metabolism on alcoholic liver injury, and the- 收稿日期:2017-08-15 基金项目:河北省自然科学基金资助项目(H2013201203);河北大学医学学科专项资金建设项目(2014A1003) 第一作者:杨飒(1992—),女,河北保定人,河北大学在读研究生.E-mail:yangsa721@163.com 通信作者:赵燕燕(1960—),女,天津人,河北大学教授,主要从事药学以及将现代分离技术用于临床、药学、食品、环境等方面的研究工作.E-mail:zhaoyany606@163.com第1期杨飒等:甘草酸差向异构体不同配比对酒精性肝损伤脂质代谢的影响optimal combination proportion is 4∶6.

Key words: 18α-glycyrrhizic, 18β-glycyrrhizic, combination proportion, alcoholic liver injury, lipid metabolism

中图分类号:

R285.5

杨飒,孙晓可,孟祥波,周程艳,赵燕燕. 甘草酸差向异构体不同配比对酒精性肝损伤脂质代谢的影响[J]. 河北大学学报(自然科学版), 2018, 38(1): 41-48.

YANG Sa, SUN Xiaoke, MENG Xiangbo, ZHOU Chengyan, ZHAO Yanyan. Effects of different proportions of 18α,β-glycyrrhizic acids on lipid metabolism on alcoholic liver injury[J]. Journal of Hebei University (Natural Science Edition), 2018, 38(1): 41-48.

参考文献

[1] LIM S, VOS T, BRUCE N.The burden of disease and injury attributable to 67 risk factors and risk factor clusters in 21 regions 1990-2010: a systematic analysis [J].Lancet, 2012, 380(9859):2224-2260.DOI:10.1016/S0140-6736(12)61766-8.
[2] 季红, 郭鑫, 尹鹏.葛根素对急性酒精性肝损伤的预防作用[J].医学综述, 2016, 22(15):3048-3049.DOI:10.3969/j.issn.1006-2084.2016.15.039. JI H, GUO X, YIN P.The Preventive action of puerarin on alcoholic liver injury [J].Medical Recapitulate.2016, 22(15):3048-3049.DOI:10.3969/j.issn.1006-2084.2016.15.039.
[3] 杨芳.魔芋葡甘聚糖对大鼠酒精性脂肪肝的预防效果[J].西北农林科技大学学报(自然科学版), 2012, 40(8):8-12.DOI:10.3969/j.issn.1006-2084.2016.15.039. YANG F.Study on the preventive effect of KGM on the rat with alcoholic fatty liver [J].Journal of Northwest A&F university( Nat Sci Ed), 2012, 40(8):8-12.DOI: 10.3969/j.issn.1006-2084.2016.15.039.
[4] MENG W, ZHANG X J, FENG K, et al.Dietary α-linolenic acid-rich flaxseed oil prevents against alcoholic hepatic steatosisviaameliorating lipid homeostasis at adipose tissue-liver axis in mice[J].Scientific Reports, 2016, 6:26826.DOI:10.1038/srep26826.
[5] 国家药典委员会.中华人民共和国药典[M].北京:化学工业出版社,2015.
[6] JUNG J C, LEE Y H, KIM S H, et al.Hepatoprotective effect of licorice, the root of Glycyrrhiza uralensis Fischer, in alcohol-induced fatty liver disease[J].Bmc Complementary & Alternative Medicine, 2015, 16(1):1-10.DOI: 10.1186/s12906-016-0997-0.
[7] 张慧, 裴志东, 陈莹,等.18α,18β-甘草酸对小鼠急性肝损伤的保护作用及其联合用药配伍比例探讨[J].中国实验方剂学杂志, 2016(2):103-106.DOI: 10.13422/j.cnki.syfjx.2016020103 ZHANG H, PEI Z D, CHEN Y, et al.Protective effect and combination proportion of 18α,18β-Glycyrrhizic acid on acute liver injury in mice[J].Chinese Journal of Experimental Traditional Medical Formulae,2016(2):103-106.DOI: 10.13422/j.cnki.syfjx.2016020103.
[8] 杨超君.甘草酸18H差向异构体对急性肝损伤小鼠血清IL-2和TNF-α的影响[J].中国中医药科技, 2016, 23(1):43-44. YANG C J.Effects of C-18H Epimers of Glycyrrhizic acid on changes of Serum IL-2 and TNF-α Levels in acute Hepatic injury mice[J].Chinese Journal of Traditional Medical Science and Technology.2016, 23(1):43-44.
[9] 赵燕燕, 孙东, 刘丽艳,等.甘草酸18位差向异构体不同配比和浓度对Caco-2细胞P-gp功能的影响[J].河北大学学报(自然科学版), 2016, 36(3):249-256.DOI: 10.3969/j.issn.1000-1565.2016.03.006. ZHAO Y Y, SUN D, LIU L Y, et al.Different proportion and concentration of Glycyrrhizic acid-18-epimers effect on P-gp function in Caco-2 cells[J].Journal of Hebei University(Natural Science Edition),2016, 36(3):249-256.DOI: 10.3969/j.issn.1000-1565.2016.03.006.
[10] KAO T C, SHYU M H, YEN G C.Glycyrrhizic acid and 18β-glycyrrhetinic acid inhibit inflammation via PI3K/Akt/GSK3β signaling and glucocorticoid receptor activation[J].Journal of Agricultural & Food Chemistry, 2010, 58(15):8623-8629.DOI: 10.1021/jf101841r.
[11] WANG C Y, KAO T C, LO W H, et al.Glycyrrhizic Acid and 18 beta-Glycyrrhetinic Acid Modulate Lipopolysaccharide-Induced Inflammatory Response by Suppression of NF-kappa B through PI3K p110 delta and p110 gamma Inhibitions[J].Journal of Agricultural & Food Chemistry, 2011, 59(14):7726-7733.DOI: 10.1021/jf2013265.
[12] 赵燕燕, 石敏健, 刘丽艳,等.4代甘草酸制剂主成分异构体及有关物质含量差异分析与变化趋势[J].药物分析杂志, 2014(2):247-254.DOI: 10.16155/j.0254-1793.2014.02.005. ZHAO Y Y, SHI M J, LIU L Y, et al.Analysis of content differences and variation trends of the principal component isomers and related substances in the four generations of glycyrrhizin preparations [J].Chin J Pharm Anal, 2014(2):247-254.DOI: 10.16155/j.0254-1793.2014.02.005.
[13] SCHWARTZ J M, REINUS J F.Prevalence and natural history of alcoholic liver disease [J].Clinics in Liver Disease, 2012, 16(4):659-666.DOI: 10.3390/molecules22020191.
[14] 白慧媛, 俸珊.五味子乙素对氯氮平致小鼠肝损伤的保护作用[J].药学学报, 2017, 52(3):390-396.DOI:10.16438/j.0513-4870.2016-0861. BAI H Y, FENG S.Protection effects of schizandrin B against liver injury induced by clozapine in mice [J].Acta Pharmaceutica Sinica,2017, 52(3): 390 -396.DOI:10.16438/j.0513-4870.2016-0861.
[15] DEVI S L, VISWANATHAN P, ANURADHA C V.Taurine enhances the metabolism and detoxification of ethanol and prevents hepatic fibrosis in rats treated with iron and alcohol[J].Environmental Toxicology & Pharmacology, 2009,27(1):120.DOI: 10.1016/j.etap.2008.09.004.
[16] RASHA M A, DINA A S, ASSER I G.Hepatoprotective effects of Astragalus kahiricus root extract against ethanol-induced liver apoptosis in rats[J].Chinese Journal of Natural Medicines, 2013,11(4):354-361.DOI: 10.3724/SP.J.1009.2013.00354.
[17] LIU J.Ethanol and liver: Recent insights into the mechanisms of ethanol-induced fatty liver.[J].World Journal of Gastroenterology, 2014, 20(40):14672-14685.DOI: 10.3748/wjg.v20.i40.14672.
[18] 冯海容, 郑轶, 常海茹,等.紫叶李果实总黄酮对大鼠酒精性肝损伤的保护作用机制研究[J].中国药房, 2017, 28(10):1332-1337.DOI: 10.6039/j.issn.1001-0408.2017.10.10. FENG H R, ZHENG Y, CHANG H R, et al.Study on the protective effect mechanism of total flavones from prunus cerasifera fruits for alcoholic liver disease in rats [J].China Pharmacy, 2017, 28(10):1332-1337.DOI: 10.6039/j.issn.1001-0408.2017.10.10.
[19] 陈淑芹, 张菁, 方启晨.胆汁酸对糖脂及能量代谢调节作用的研究进展[J].医学综述, 2016, 22(5):947-950.DOI: 10.3969/j.issn.1006-2084.2016.05.032. CHEN S Q, ZHANG J, FANG Q C.Recent progress of the role of bile acids in regulating glucose, lipid and energy Metabolism [J].Medical Recapitulate, 2016, 22(5):947-950.DOI: 10.3969/j.issn.1006-2084.2016.05.032.
[20] FENG L J, YU C H, YING K J.Hypolipidemic and antioxidant effects of total flavonoids of Perilla Frutescens, leaves in hyperlipidemia rats induced by high-fat diet[J].Food Research International, 2011, 44(1):404-409.DOI: 10.1016/j.foodres.2010.09.035.