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中国临床药理学与治疗学 ›› 2023, Vol. 28 ›› Issue (6): 609-616.doi: 10.12092/j.issn.1009-2501.2023.06.002

• 基础研究 • 上一篇    下一篇

桑葚改善大鼠非酒精性脂肪性肝病的氧化应激损伤

汪东辉1,蒋素文1,胡爱荣1,朱  波1,何哲耘1,张露侃2,王家岚3,范  莹4,林  恳2   

  1. 1宁波市第二医院肝病精准诊治中心,宁波  315020,浙江;
    2宁波大学医学院,宁波  315211,浙江;
    3温州医科大学研究生院,温州  325035,浙江;
    4绍兴文理学院医学院,绍兴  312000,浙江

  • 收稿日期:2023-01-03 修回日期:2023-05-09 出版日期:2023-06-26 发布日期:2023-07-12
  • 通讯作者: 胡爱荣,男,硕士,主任医师,研究方向:感染病与肝病的基础与临床研究。 E-mail:huairong@ucas.edu.cn
  • 作者简介:汪东辉,男,硕士,主治医师,研究方向:中医药防治非酒精性脂肪肝的效应成分筛选及作用机制研究。 E-mail:har1224@126.com
  • 基金资助:
    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)

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

WANG Donghui1, JIANG Suwen1, HU Airong1, ZHU Bo1, HE Zheyun1, ZHANG Lukan2, WANG Jialan3, FAN Ying4, LIN Ken2    

  1. 1 Precision Diagnosis and Treatment Center of Liver Diseases, Ningbo No. 2 Hospital, Ningbo 315020, Zhejiang, China; 2Medical School of Ningbo University, Ningbo 315211, Zhejiang, China; 3Graduate School, Wenzhou Medical University, Wenzhou 325035, Zhejiang, China; 4Medical School of Shaoxing University, Shaoxing 312000, Zhejiang, China
  • Received:2023-01-03 Revised:2023-05-09 Online:2023-06-26 Published:2023-07-12

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。

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

Abstract:

AIM: To explore the effects of mulberry on antioxidant stress injury in rats with nonalcoholic fatty liver disease (NAFLD) induced by high-fat 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 real-time qPCR. RESULTS: Compared with the normal group: the levels of MDA in liver homogenate increased. The levels of ATP, the gene expressions of γ-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 of γ-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.

Key words: mulberry, nonalcoholic fatty liver disease, rats, oxidative stress, nuclear factor-E2-related factor 2, antioxidant response element

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