甘草酸配伍蛇床子素对大鼠酒精性脂肪肝的治疗作用

恽菲; 康安; 狄留庆; 刘若囡; 徐晓琰

甘草酸配伍蛇床子素对大鼠酒精性脂肪肝的治疗作用

恽菲^1,2,
康安^2,3,
狄留庆^2,3,,
刘若囡²,
徐晓琰²

1.
江苏联合职业技术学院常州卫生分院，江苏常州 213002
2.
南京中医药大学药学院，江苏南京 210023
3.
江苏省中药高效给药系统工程技术研究中心，江苏南京 210023

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出版历程
- 收稿日期: 2017-12-20
- 刊出日期: 2018-09-10

Therapeutic Compatibility Effect of Glycyrrhizin and Osthole on the Treatment of Alcoholic Fatty Liver in Rats

YUNFei^1,2,
KANGAn^2,3,
DILiu-qing^{2,3
,},
LIURuo-nan²,
XUXiao-yan²

1.
Changzhou Hygiene Vocational Technology College, Jiangsu Union Technical Institute, Changzhou, 213002, China
2.
College of Pharmacy, Nanjing University of Chinese Medicine, Nanjing, 210023, China
3.
Jiangsu Engineering Research Center for Efficient Delivery System of TCM, Nanjing, 210023, China

摘要

摘要: 目的研究甘草酸配伍蛇床子素对大鼠酒精性脂肪肝的治疗影响，初步探讨组分配伍的作用机制。方法建立大鼠酒精性脂肪肝模型后，随机分为正常组、模型组、阳性药（力平之）组、蛇床子素组（Ost）、甘草酸组(GL)、蛇床子素与甘草酸配伍高、中、低剂量组。治疗组从实验第5周起，分别给予药物灌胃：阳性药组ig力平之20 mg/(kg·d)，蛇床子素组10 mg/(kg·d) ig，甘草酸组22.5 mg/(kg·d) ig，配伍低剂量组为ig蛇床子素5 mg/(kg·d)和甘草酸11.25 mg/(kg·d)，配伍中剂量组为ig蛇床子素10 mg/(kg·d)和甘草酸22.5 mg/(kg·d)，配伍高剂量组为ig蛇床子素20 mg/(kg·d)和甘草酸45 mg/(kg·d)，正常组和模型组灌胃等体积的生理盐水连续灌胃6周。末次给药后，观察大鼠一般情况；光镜观察肝脏的病理变化，同时分别测定大鼠血清门冬氨酸氨基转移酶(AST)、碱性磷酸酶(AKP)、谷丙转氨酶(ALT)水平以及肝组织匀浆中总胆固醇(TC)、甘油三酯(TG)、超氧化物歧化酶(SOD)和丙二醛(MDA)含量；Western blot法检测大鼠肝组织PPARα蛋白的表达情况。结果各治疗组与模型组比较，肝组织病理变化有不同程度的改善；甘草酸配伍蛇床子素中剂量和高剂量组能显著降低血清ALT、AST和AKP水平（P<0.05）；大鼠肝组织药理活性测试结果显示配伍中剂量和高剂量组能显著降低肝组织MDA含量，提高SOD的活性，差异具有统计学意义（P<0.01），配伍中剂量组能显著降低大鼠肝脏TG和TC含量（P<0.05）；Western blot结果表明，各治疗组PPARα蛋白水平与模型组相比有不同程度上调，而配伍中剂量和高剂量组肝组织中PPARα蛋白水平表达量显著上调，具有统计学意义（P<0.01）。结论甘草酸与蛇床子素合理的组分配伍能协同治疗酒精性脂肪肝，可能通过配伍改善肝脏功能、调节脂肪代谢、抗脂质氧化作用和增加PPARα蛋白的表达，促使损伤的肝组织得以修复。
- 甘草酸配伍蛇床子素 /
- 酒精性脂肪肝 /
- 大鼠
Abstract: OBJECTIVE To study the effect of glycyrrhizin acid and osthole on the treatment of alcoholic fatty liver in rats， and to explore the mechanism of compatibility of components. METHODS After the establishment of rat alcoholic fatty liver， the rats were randomly divided into normal group， model group， positive drug group (Lipingzhi)， osthole (Ost) group， glycyrrhizic acid (GL) group， high dose group of osthole and glycyrrhizic acid， medium dose group of osthole and glycyrrhizic acid and low dose group of osthole and glycyrrhizic acid. The treatment groups were given by gastrogavage every day starting from the 5th week， the positive group ig. Lipingzhi 20 mg/(kg·d)， the osthole group ig. Ost 10 mg/(kg·d)， the glycyrrhizic acid group ig. GL 22.5 mg/( kg·d)， the low dose group ig. the compatibility components of Ost 5 mg/(kg·d) and GL 11.25 mg/(kg·d)， the medium dose group ig. Ost 10 mg/(kg·d) and GL 22.5 mg/(kg·d)， the high dose group ig. Ost 20 mg/(kg·d) and GL 45 mg/(kg·d) and the normal and model group were given distilled water with equal volume for 6 weeks. We observed the sign of rats， the pathological changes of liver with the optical microscope. Then we measured AST， AKP and ALT changes in rat serum and TC， TG， SOD and MDA contents in liver homogenate. The expression of PPARα protein in liver tissue was examined using Western blot method. RESULTS Compared with the model group， the pathological changes of liver tissue were improved in different treatment groups and the ALT， AST and AKP levels in serum were significantly decreased in the groups of glycyrrhizin combined with osthole at medium and high doses(P<0.05). The liver tissue of rats test results showed the medium dose and high dose groups of glycyrrhizin combined with osthole could significantly reduce the content of MDA and improve the activity of SOD. There were significant differences among the model group and the treatment groups at medium and high doses (P<0.01). The TG and TC levels in the group of glycyrrhizin combined with osthole in medium dose were lower than the model group(P<0.05). Western blot results showed that the PPARα protein levels in treatment groups compared with the model group had a different degree of increase， and the compatibility of medium dose and high-dose groups in the liver tissue of PPARα protein expression was up-regulated with statistical significance (P<0.01). CONCLUSION The reasonable combination of glycyrrhizic acid and osthole had synergistic treatment on alcoholic fatty liver， and its main mechanism might be related to the improving of liver function， regulation of fat metabolism， anti-lipid oxidation and the increased protein expression of PPARα.
- glycyrrhizin acid and osthole /
- alcoholic fatty liver /
- rat

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参考文献(16)

[1]	宋芳，谢梅林，朱路佳，等．蛇床子素调节酒精性脂肪肝大鼠脂代谢机制的研究[J]．中国药理学通报，2008， 24（7）：979-980．
[2]	SUN F， XIE ML， XUE J， et al. Osthol regulates hepatic PPAR alpha-mediated lipogenic gene expression in alcoholic fatty liver murine[J]. Phytomedicine， 2010， 17(8/9): 669-673.
[3]	SUN F， XIE ML， ZHU LJ， et al. Inhibitory effect of osthole on alcohol-induced fatty liver in mice[J]. Dig Liver Dis， 2009， 41(2): 127-133.
[4]	ZHANG J， XUE J， WANG H， et al. Osthole improves alcohol-induced fatty liver in mice by reduction of hepatic oxidative stress[J]. Phytother Res， 2011， 25(5): 638-643.
[5]	YUN F， KANG A， SHAN JJ， et al. A rapid and sensitive LC-MS/MS method for the determination of osthole in rat plasma: application to pharmacokinetic study[J]. Biomed Chromatogr， 2013， 27(5): 676-680.
[6]	YUN F， KANG A， SHAN J， et al. Preparation of osthole-polymer solid dispersions by hot-melt extrusion for dissolution and bioavailability enhancement[J]. Int J Pharm， 2014， 465(1/2): 436-443.
[7]	恽菲，狄留庆，陈乐天，等.蛇床子素体内过程及其组分配伍和药剂学技术应用影响研究[J].中国实验方剂学杂志，2013，14(19):347-350.
[8]	TANAKA M， TAKAHASHI M， KUWAHARA E， et al. Effect of glycyrrhizinate on dissolution behavior and rectal absorption of amphotericin B in rabbits[J]. Chem Pharm Bull， 1992， 40(6): 1559-1562.
[9]	POLYAKOV NE， KHAN VK， TARABAN MB， et al. Complex of Calcium receptor blocker nifedipine with glycyrrhizic acid[J]. J Phys Chem B， 2008， 112(14): 4435-4440.
[10]	POLYAKOV NE， LESHINA TV， SALAKHUTDINOV NF， et al. Host-guest complexes of carotenoids with beta-glycyrrhizic acid[J]. J Phys Chem B， 2006， 110(13): 6991-6998.
[11]	陈乐天，狄留庆，刘卉，等．甘草提取物对瑞香素大鼠体内药代动力学特征的影响研究[J]．中国中药杂志，2011， 36（7）：935-938．
[12]	EU CH， LIM WY， TON SH， et al. Glycyrrhizic acid improved lipoprotein lipase expression， insulin sensitivity， serum lipid and lipid deposition in high-fat diet-induced obese rats[J]. Lipids Health Dis， 2010， 9: 81.
[13]	OGIKU M， KONO H， HARA M， et al. Glycyrrhizin prevents liver injury by inhibition of high-mobility group box 1 production by Kupffer cells after ischemia-reperfusion in rats[J]. J Pharmacol Exp Ther， 2011， 339(1): 93-98.
[14]	恽菲．组分配伍与药剂学技术应用对蛇床子素生物有效性的影响及其机制研究[D]．南京：南京中医药大学，2014．
[15]	KASDALLAH-GRISSA A， MORNAGUI B， AOUANI E， et al. Protective effect of resveratrol on ethanol-induced lipid peroxidation in rats[J]. Alcohol Alcohol， 2006， 41(3): 236-239.
[16]	陶妍，吴高峰，杨建成，等．PPAR-α在酒精性脂肪肝发生中的作用研究进展[J]．动物医学进展，2012， 33（2）：71-74．