人参皂苷Rb1对小鼠非酒精性脂肪肝病的治疗作用及其机制
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摘要
目的观察人参皂苷Rb1对小鼠非酒精性脂肪肝病(NAFLD)的治疗作用,初步探讨其机制。方法将C57BL/6小鼠40只分为正常对照组、模型对照组、低剂量组和高剂量组。模型对照组、低剂量组和高剂量组给予胆碱蛋氨酸缺乏饮食4周制作NAFLD模型,高剂量组和低剂量组小鼠通过灌胃分别给予80、40 mg/(kg·d)的Rb1,1次/d。给药15 d后处死各组小鼠,采用全自动生化分析仪检测小鼠血浆总胆固醇(TC)、总甘油三酯(TG)、谷丙转氨酶(ALT)、谷草转氨酶(AST);取小鼠肝组织进行HE染色观察肝组织病理变化;采用ELISA法检测肝组织中的丙二醛(MDA)、超氧化物歧化酶(SOD)。结果模型对照组、低剂量组、高剂量组小鼠体质量、肝质量、脾质量、脾脏系数均低于正常对照组(P均<0.01)。模型对照组、低剂量组、高剂量组血浆ALT、AST水平均高于正常对照组(P均<0.01),高剂量组血浆ALT、AST水平低于模型对照组和低剂量组(P均<0.05),低剂量组血浆AST水平低于模型对照组(P<0.05)。模型对照组、低剂量组、高剂量组TC、TG水平均低于正常对照组(P均<0.05);高剂量组TC水平高于模型对照组,TG水平高于低剂量组(P均<0.05)。低剂量组和高剂量组脂肪变性均有所减轻,脂滴大小不一,其中高剂量组血管周围炎细胞浸润程度明显好转。模型对照组、低剂量组、高剂量组小鼠肝组织中MDA、SOD表达均高于正常对照组,高剂量组肝组织中MDA表达低于模型对照组和低剂量组,低剂量组、高剂量组肝组织中SOD表达均低于模型对照组(P均<0.01)。结论 Rb1灌胃治疗小鼠NAFLD能够改善肝功能,调节血脂水平,减轻肝脏脂肪堆积;Rb1可能通过减轻脂质过氧化而起到治疗NAFLD的作用。
Objective To explore the therapeutical effect of ginsenoside Rb1 on non-alcoholic fatty liver disease(NAFLD) in mice, and to discuss its possible mechanisms.Methods Forty C57 BL/6 mice were randomly divided into four groups: the normal group, model control group, low-dose group, and high-dose group. NAFLD models were established in the model control group, low-dose group, and high-dose group by methionine-choline-deficient(MCD) diet for about 4 weeks. Then, the rats in the low-dose group and high-dose group were administered 80 and 40 mg/(kg·d) ginsenoside Rb1, and once a day. After 15-day administration, all mice were sacrificed. We detected the TC, TG, ALT, and AST in the plasma using fully automatic biochemical analyser. Meanwhile, the pathological changes of liver were observed under light microscope after HE staining. We measured the MDA and superoxide dismutase(SOD) of liver tissues by ELISA. Results The body mass, liver mass, spleen mass, and spleen coefficient of mice were all lower in the model control group, low-dose group and high-dose group than in the normal group(all P<0. 01). The ALT and AST levels in plasma of the model control group, low-dose group and high-dose group were all higher than those in the normal group(all P<0. 01); the ALT and AST levels in plasma of the high-dose group were all lower than those in the model control group and low-dose group(both P<0.05); and the AST in plasma of the low-dose group was lower than that in the model control group(P<0.05). The TC and TG in plasma of the model control group, low-dose group, and high-dose group were all lower than those in the normal group(all P<0.05). The TC in plasma of the high-dose group was higher than that in the model control group, and its TG in plasma was higher than that in the low-dose group(both P<0.05). The fatty degeneration of liver was improved in the low-dose group and high-dose group, there were varying sizes of lipid droplets, and the inflammatory cell infiltration around blood vessels had obvious improvement in the high-dose group. The MDA and SOD expression in the liver tissues of the model control group, low-dose group and high-dose group were all higher than those in the normal group, the MDA expression of the high-dose group was lower than that in the model control group and low-dose group, and the SOD expression of the low-dose group and high-dose group were all lower than that in the model control group(all P<0.01).Conclusions Ginsenoside Rb1 can improve the liver function of NAFLD mice, regulate the blood lipid and reduce liver fat accumulation. Therefore, Rb1 may play a role in the treatment of NAFLD by reducing lipid peroxidation.
Objective To explore the therapeutical effect of ginsenoside Rb1 on non-alcoholic fatty liver disease(NAFLD) in mice, and to discuss its possible mechanisms.Methods Forty C57 BL/6 mice were randomly divided into four groups: the normal group, model control group, low-dose group, and high-dose group. NAFLD models were established in the model control group, low-dose group, and high-dose group by methionine-choline-deficient(MCD) diet for about 4 weeks. Then, the rats in the low-dose group and high-dose group were administered 80 and 40 mg/(kg·d) ginsenoside Rb1, and once a day. After 15-day administration, all mice were sacrificed. We detected the TC, TG, ALT, and AST in the plasma using fully automatic biochemical analyser. Meanwhile, the pathological changes of liver were observed under light microscope after HE staining. We measured the MDA and superoxide dismutase(SOD) of liver tissues by ELISA. Results The body mass, liver mass, spleen mass, and spleen coefficient of mice were all lower in the model control group, low-dose group and high-dose group than in the normal group(all P<0. 01). The ALT and AST levels in plasma of the model control group, low-dose group and high-dose group were all higher than those in the normal group(all P<0. 01); the ALT and AST levels in plasma of the high-dose group were all lower than those in the model control group and low-dose group(both P<0.05); and the AST in plasma of the low-dose group was lower than that in the model control group(P<0.05). The TC and TG in plasma of the model control group, low-dose group, and high-dose group were all lower than those in the normal group(all P<0.05). The TC in plasma of the high-dose group was higher than that in the model control group, and its TG in plasma was higher than that in the low-dose group(both P<0.05). The fatty degeneration of liver was improved in the low-dose group and high-dose group, there were varying sizes of lipid droplets, and the inflammatory cell infiltration around blood vessels had obvious improvement in the high-dose group. The MDA and SOD expression in the liver tissues of the model control group, low-dose group and high-dose group were all higher than those in the normal group, the MDA expression of the high-dose group was lower than that in the model control group and low-dose group, and the SOD expression of the low-dose group and high-dose group were all lower than that in the model control group(all P<0.01).Conclusions Ginsenoside Rb1 can improve the liver function of NAFLD mice, regulate the blood lipid and reduce liver fat accumulation. Therefore, Rb1 may play a role in the treatment of NAFLD by reducing lipid peroxidation.
引文
[1] Younossi ZM, Marchesini G, Pinto-Cortez H, et al. Epidemiology of nonalcoholic fatty liver disease and nonalcoholic steatohepatitis: implications for liver transplantation[J]. Transplantation, 2019,103(1):22-27.
[2] Yang H, Li D, Song X, et al. Joint associations of serum uric acid and ALT with NAFLD in elderly men and women: a Chinese cross-sectional study[J]. J Transl Med, 2018,16(1):285.
[3] Tomasiewicz K, Flisiak R, Halota W, et al. Recommendations for the management of non-alcoholic fatty liver disease (NAFLD)[J]. Clin Exp Hepatol, 2018,4(3):153-157.
[4] 张聪,黄一沁,陈洁.非酒精性脂肪性肝病的生活干预疗法研究进展[J].山东医药,2018,58(2):105-107.
[5] Tang Y, Cao G, Min X, et al. Cathepsin B inhibition ameliorates the non-alcoholic steatohepatitis through suppressing caspase-1 activation[J]. J Physiol Biochem, 2018,74(4):503-510.
[6] Lee S, Son B, Jeon J, et al. Decreased hepatic lactotransferrin induces hepatic steatosis in chronic non-alcoholic fatty liver disease model[J]. Cell Physiol Biochem, 2018,47(6):2233-2249.
[7] Ryu KJ, Park H, Kim YJ, et al. Moderate to severe vasomotor symptoms are risk factors for non-alcoholic fatty liver disease in postmenopausal women[J]. Maturitas, 2018,117(11):22-28.
[8] Ruzman L, Mikolasevic I, Baraba Dekanic K, et al. Advances in diagnosis of chronic liver diseases in pediatric patients[J]. World J Pediatr, 2018,14(6):541-547.
[9] Okubo H, Kushiyama A, Nakatsu Y, et al. Roles of gut-derived secretory factors in the pathogenesis of non-alcoholic fatty liver disease and their possible clinical applications[J]. Int J Mol Sci, 2018,19(10):3064.
[10] Nseir WB, Mograbi JM, Amara AE, et al. Nonalcoholic fatty liver disease and 30-day all-cause mortality in adult patients with community-acquired pneumonia[J]. Qjm, 2019,112(2):95-99.
[11] 朱振红,郭朋,唐旭东,等.脂肪肝从毒论治[J].辽宁中医杂志,2014,41(12):2568-2570.
[12] 刘官成,元海丹,朴光春.人参花提取物对酒精性脂肪肝的抑制作用[J].延边大学医学学报,2015,38(4):292-294.
[13] 陈静,祁东利,张春风,等.人参皂苷Rb1对油酸诱导HepG2细胞脂肪堆积的影响作用[J].中国野生植物资源,2013,32(2):20-23.
[14] 彭璇,黄德斌,严米娅,等.人参皂苷Rg1通过调节脂肪代谢改善非酒精性脂肪肝病大鼠的肝功能[J].中国病理生理杂志,2015,31(5):864-870.
[15] Shen L, Xiong Y, Wang DQ, et al. Ginsenoside Rb1 reduces fatty liver by activating AMP-activated protein kinase in obese rats[J]. J Lipid Res, 2013,54(5):1430-1438.
[16] Kim D, Kim W, Joo SK, et al. Predictors of nonalcoholic steatohepatitis and significant fibrosis in non-obese nonalcoholic fatty Liver disease[J]. Liver Int, 2019,39(2):332-341.
[17] 冯巩,贺娜,王菊宁,等.非酒精性脂肪性肝病的流行病学与血清无创诊断研究进展[J].中华肝脏病杂志,2018,26(6):476-480.
[18] Carter A, Brackley SM, Gao J, et al. The global prevalence and genetic spectrum of lysosomal acid lipase deficiency: a rare condition that mimics NAFLD[J]. J Hepatol, 2019,70(1):142-150.
[19] Liu L, Zhou Y, Dai D, et al. Protective effects of Kangxian ruangan capsule against nonalcoholic fatty liver disease fibrosis in rats induced by MCD diet[J]. Biomed Pharmacother, 2018,108(12):424-434.
[20] Dongiovanni P, Meroni M, Baselli GA, et al. Insulin resistance promotes Lysyl Oxidase Like 2 induction and fibrosis accumulation in non-alcoholic fatty liver disease[J]. Clin Sci (Lond), 2017,131(12):1301-1315.
[2] Yang H, Li D, Song X, et al. Joint associations of serum uric acid and ALT with NAFLD in elderly men and women: a Chinese cross-sectional study[J]. J Transl Med, 2018,16(1):285.
[3] Tomasiewicz K, Flisiak R, Halota W, et al. Recommendations for the management of non-alcoholic fatty liver disease (NAFLD)[J]. Clin Exp Hepatol, 2018,4(3):153-157.
[4] 张聪,黄一沁,陈洁.非酒精性脂肪性肝病的生活干预疗法研究进展[J].山东医药,2018,58(2):105-107.
[5] Tang Y, Cao G, Min X, et al. Cathepsin B inhibition ameliorates the non-alcoholic steatohepatitis through suppressing caspase-1 activation[J]. J Physiol Biochem, 2018,74(4):503-510.
[6] Lee S, Son B, Jeon J, et al. Decreased hepatic lactotransferrin induces hepatic steatosis in chronic non-alcoholic fatty liver disease model[J]. Cell Physiol Biochem, 2018,47(6):2233-2249.
[7] Ryu KJ, Park H, Kim YJ, et al. Moderate to severe vasomotor symptoms are risk factors for non-alcoholic fatty liver disease in postmenopausal women[J]. Maturitas, 2018,117(11):22-28.
[8] Ruzman L, Mikolasevic I, Baraba Dekanic K, et al. Advances in diagnosis of chronic liver diseases in pediatric patients[J]. World J Pediatr, 2018,14(6):541-547.
[9] Okubo H, Kushiyama A, Nakatsu Y, et al. Roles of gut-derived secretory factors in the pathogenesis of non-alcoholic fatty liver disease and their possible clinical applications[J]. Int J Mol Sci, 2018,19(10):3064.
[10] Nseir WB, Mograbi JM, Amara AE, et al. Nonalcoholic fatty liver disease and 30-day all-cause mortality in adult patients with community-acquired pneumonia[J]. Qjm, 2019,112(2):95-99.
[11] 朱振红,郭朋,唐旭东,等.脂肪肝从毒论治[J].辽宁中医杂志,2014,41(12):2568-2570.
[12] 刘官成,元海丹,朴光春.人参花提取物对酒精性脂肪肝的抑制作用[J].延边大学医学学报,2015,38(4):292-294.
[13] 陈静,祁东利,张春风,等.人参皂苷Rb1对油酸诱导HepG2细胞脂肪堆积的影响作用[J].中国野生植物资源,2013,32(2):20-23.
[14] 彭璇,黄德斌,严米娅,等.人参皂苷Rg1通过调节脂肪代谢改善非酒精性脂肪肝病大鼠的肝功能[J].中国病理生理杂志,2015,31(5):864-870.
[15] Shen L, Xiong Y, Wang DQ, et al. Ginsenoside Rb1 reduces fatty liver by activating AMP-activated protein kinase in obese rats[J]. J Lipid Res, 2013,54(5):1430-1438.
[16] Kim D, Kim W, Joo SK, et al. Predictors of nonalcoholic steatohepatitis and significant fibrosis in non-obese nonalcoholic fatty Liver disease[J]. Liver Int, 2019,39(2):332-341.
[17] 冯巩,贺娜,王菊宁,等.非酒精性脂肪性肝病的流行病学与血清无创诊断研究进展[J].中华肝脏病杂志,2018,26(6):476-480.
[18] Carter A, Brackley SM, Gao J, et al. The global prevalence and genetic spectrum of lysosomal acid lipase deficiency: a rare condition that mimics NAFLD[J]. J Hepatol, 2019,70(1):142-150.
[19] Liu L, Zhou Y, Dai D, et al. Protective effects of Kangxian ruangan capsule against nonalcoholic fatty liver disease fibrosis in rats induced by MCD diet[J]. Biomed Pharmacother, 2018,108(12):424-434.
[20] Dongiovanni P, Meroni M, Baselli GA, et al. Insulin resistance promotes Lysyl Oxidase Like 2 induction and fibrosis accumulation in non-alcoholic fatty liver disease[J]. Clin Sci (Lond), 2017,131(12):1301-1315.
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