桑葚改善大鼠非酒精性脂肪性肝病的氧化应激损伤  

Mulberry exerts antioxidant stress effect in rats with nonalcoholic fatty liver disease

作　　者：汪东辉 蒋素文[1] 胡爱荣[1] 朱波[1] 何哲耘 张露侃 王家岚 范莹 林恳 WANG Donghui;JIANG Suwen;HU Airong;ZHU Bo;HE Zheyun;ZHANG Lukan;WANG Jialan;FAN Ying;LIN Ken(Precision Diagnosis and Treatment Center of Liver Diseases,Ningbo No.2 Hospital,Ningbo 315020,Zhejiang,China;Medical School of Ningbo University,Ningbo 315211,Zhejiang,China;Graduate School,Wenzhou Medical University,Wenzhou 325035,Zhejiang,China;Medical School of Shaoxing University,Shaoxing 312000,Zhejiang,China)

机构地区：[1]宁波市第二医院肝病精准诊治中心,浙江宁波315020 [2]宁波大学医学院,浙江宁波315211 [3]温州医科大学研究生院,浙江温州325035 [4]绍兴文理学院医学院,浙江绍兴312000

出　　处：《中国临床药理学与治疗学》2023年第6期609-616,共8页Chinese Journal of Clinical Pharmacology and Therapeutics

基　　金：宁波市自然基金项目(202003N4209);浙江省宁波市共建医学重点学科项目(2016-S04)。

摘　　要：目的:探讨桑葚对大鼠非酒精性脂肪性肝病(NAFLD)氧化应激损伤的改善作用。方法:10只SD雄性大鼠为正常组,50只NAFLD造模SD大鼠(高脂饮食持续造模8周)于第9周起随机分为模型组、桑葚低、中、高剂量组(2.5 g/kg、5.0 g/kg、10.0 g/kg)、异甘草酸镁阳性对照组(原液稀释至1.0 g/L,15 mL·kg^(-1)·d^(-1)),每组10只,连续灌胃6周。测定大鼠肝组织匀浆丙二醛(MDA)、腺苷三磷酸(ATP)水平,HE染色及油红O染色观察肝脏病理变化及脂肪沉积状况,Real-time qPCR检测肝组织转录因子NF-E2相关因子2(Nrf2)-抗氧化反应元件(ARE)相关基因[Nrf2、I型血红素抗氧化酶(HO-1)、谷氨酰半胱氨酸合成酶(γ-GCS)及谷胱甘肽S-转移酶P-1(GSTP-1)]的表达。结果:与正常组比较:模型组大鼠肝组织MDA水平显著升高,肝组织ATP水平及γ-GCS、GSTP-1、HO-1、Nrf2基因相对表达量均明显下降(P<0.01);肝脏脂肪沉积明显,肝脂肪变显著。与模型组相比:桑葚各剂量组大鼠肝组织MDA水平均显著下降(P<0.05),呈剂量依赖性;桑葚中、高剂量组大鼠肝组织ATP水平、γ-GCS及Nrf2基因相对表达量均显著上升(P<0.05),桑葚低、中、高剂量组大鼠肝组织GSTP-1及HO-1基因相对表达量显著上升(P<0.05);肝脂肪沉积改善显著,肝脂肪变不同程度改善。结论:桑葚对高脂饮食诱导NAFLD大鼠肝脂肪变有较好的预防保护功效,并可能通过影响Nrf2-ARE相关基因的表达发挥抗氧化应激效应。AIM:To explore the effects of mulberry on antioxidant stress injury in rats with nonalcoholic fatty liver disease(NAFLD)induced by highfat diet.METHODS:Sixty male Sprague-Dawley rats were randomly divided into normal group(10 rats)and model making group(50 rats,high-fat feed for 8 weeks).From the 9th week,the NAFLD rats were randomly divided into model group,intervention groups(mulberry low,moderate,and high dosage,2.5 g/kg,5.0 g/kg,and 10.0 g/kg,respectively),and positive control group(magnesium isoglycyrrhizinate,the original solution diluted to 1.0 g/L,15 mL·kg^(-1)·d^(-1)),10 rats per group,and were gavaged once daily for 6 weeks.The levels of malondiaIdehyde(MDA)and adenosine triph osphate(ATP)in liver homogenate were measured.The HE staining and the oil red O staining were used to observe the distribution of lipid droplets and the pathologic changes of liver tissue.The gene expressions of nuclear factor-E2-related factor 2(Nrf2)-antioxidant response element(ARE)[Nrf2,heme oxygenase-1(HO-1),γ-glutamylcysteine synthetase(γ-GCS)and glutathione S-transferase P-1(GSTP-1)]in liver were detected by realtime qPCR.RESULTS:Compared with the normal group:the levels of MDA in liver homogenate increased.The levels of ATP,the gene expressions ofγ-GCS,GSTP-1,HO-1 and Nrf2 in liver were significantly decreased(P<0.01).Liver fat deposition was obvious,liver steatosis became significant.Compared with the model group:with the increase of mulberry dosage,the MDA level in liver homogenate decreased(P<0.05),the gene expressions of GSTP-1 and HO-1 increased(P<0.05),liver steatosis gradually decreased.The liver ATP level,the gene expressions ofγ-GCS and Nrf2 in moderate dosage group and high dosage group were significantly increased(P<0.05).CONCLUSION:Mulberry has a good preventive and protective effect on liver steatosis of NAFLD in rats,and may play antioxidant stress effect by affecting the expression of Nrf2-ARE related genes.

关 键 词：桑葚 非酒精性脂肪性肝病 大鼠 氧化应激 转录因子NF-E2相关因子2 抗氧化反应元件 

分 类 号：R965.2[医药卫生—药理学]