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《天津医科大学学报》[ISSN:1006-8147/CN:12-1259/R]

卷:

24卷

期数:

2018年02期

页码:

112-115,121

栏目:

出版日期:

2018-03-20

文章信息/Info

Title:

Effect of Haobie yangyin ruanjian prescription on Nrf2/HO-1 signaling pathway in ConA-induced hepatic fibrosis

作者:

卢娜; 方步武

天津医科大学药理学系，天津 300070

Author(s):

LU Na;  FANG Bu-wu

Department of Pharmacology, Tianjin Medical University, Tianjin 300070,China

关键词:

肝纤维化; 蒿鳖养阴软坚方; 刀豆球蛋白A; Nrf2; HO-1

Keywords:

hepatic fibrosis;  Haobie yangyin ruanjian prescription;  ConA;  Nrf2;  HO-1

分类号:

R575

DOI:

-

文献标志码:

A

摘要:

目的：探讨蒿鳖养阴软坚方对刀豆球蛋白A（ConA）诱导的肝纤维化Nrf2/HO-1信号通路的影响。方法：Balb/c小鼠随机分为正常、模型、秋水仙碱和蒿鳖养阴软坚方低、中、高剂量(1.16 g/kg、3.36 g/kg、11.58 g/kg)组。除正常组外，剩余各组均尾静脉注射1.5 mg/mL ConA，每周1次，持续10周。取小鼠肝脏作病理切片，观察肝脏的病理变化，检测肝组织羟脯氨酸浓度，免疫组化法检测肝组织Nrf2、HO-1蛋白的表达情况。结果：与模型组比较，蒿鳖养阴软坚方各剂量组能不同程度地减轻肝组织的炎症反应和降低肝组织羟脯氨酸的浓度，显著减轻肝纤维化程度（P＜0.05）；随着蒿鳖养阴软坚方浓度增加，Nrf2和HO-1的阳性表达逐渐增强。结论：蒿鳖养阴软坚方对Nrf2/HO-1信号通路具有激活作用，且该作用可能为其抗肝纤维化机制之一。

Abstract:

Objective: To explore the effect of Haobie yangyin ruanjian prescription (HYRP) on Nrf2/HO-1 signaling pathway in ConA-induced hepatic fibrosis. Methods: Balb/c mice were randomly divided into normal control group, model control group, colchicine group, and HYRP groups(1.16 g/kg，3.36 g/kg，11.58 g/kg). Except for the normal control group, 1.5 mg/mL ConA was given to each mouse through the tail vein once a week for 10 weeks. The concentration of hydroxyproline（Hyp）and observing liver pathological changes in liver tissues were measured, and the expression of Nrf2 and HO-1 protein in liver tissues were detected by immunohistochemistry. Results: Compared with model control group, groups of 1.16 g/kg，3.36 g/kg and 11.58 g/kg of HYRP could reduce the inflammatory reaction and decrease the concentration of Hyp in liver tissues, and significantly reduce the degree of hepatic fibrosis (P＜0.05). With the increase of HYRP concentration，the positive expressions of Nrf2 and HO-1 gradually increased. Conclusion: HYRP can activate the expression of Nrf2/HO-1 signaling pathway in liver fibrosis induced by ConA, which may be related the anti-fibrotic effects of HYRP.

参考文献/References:

[1] Seki E, Brenner D A. Recent advancement of molecular mechanisms of liver fibrosis[J]. J Hepatobiliary Pancreat Sci, 2015, 22(7): 512
[2] Friedman S L. Hepatic fibrosis: emerging therapies[J]. Dig Dis, 2015, 33(4): 504
[3] Loboda A, Damulewicz M, Pyza E A, et al. Role of Nrf2/HO-1 system in development, oxidative stress response and diseases: an evolutionarily conserved mechanism[J]. Cell Mol Life Sci , 2016, 73(17): 3221
[4] 刘红艳，方步武，率红莉，等．蒿鳖养阴软坚方对肝纤维化大鼠抗氧化损伤与诱导凋亡的作用[J]．天津医药，2010，38（10）：884
[5] 张永进，方步武．蒿鳖养阴软坚方药物血清对肝星状细胞的作用[J]．中药药理与临床，2011，27（1）：89
[6] Ren F, Chen X, Hesketh J, et al. Selenium promotes T-cell response to TCR-stimulation and ConA,but not PHA in primary porcine splenocytes[J]. PLoS One, 2012, 7(4): e35375
[7] Jamall I S, Finelli V N. Que Hee S S. A simple method to determine nanogram levels of 4-hydroxyproline in biological tissues[J]. Anal Biochem, 1981, 112(1): 70
[8] Chen B, Lu Y, Chen Y, et al. The role of Nrf2 in oxidative stress-induced endothelial injuries[J]. J Endocrinol, 2015, 225(3): 83
[9] Tell G, Gustincich S. Redox state, oxidative stress, and molecular mechanisms of protective and toxic effects of bilirubin on cells[J]. Curr Pharm Des, 2009, 15(25): 2908
[10] Farina M, Avila D S, Da Rocha J B, et al. Metals,oxidative stress and neurodegeneration:a focus on iron,mangenese and mercury[J]. Neurochem Int, 2013, 62(5): 575
[11] Fireman E. Ultrafine and nanoparticles-induced oxidative stress: the role of heme oxygenase-1 and carbon monoxide as anti-inflammatory pathways[J]. J Asthma, 2012, 49(1): 8
[12] Wang H X, Liu M, Weng S Y, et al. Immune mechanisms of concanavalin A model of autoimmune hepatitis[J]. World J Gastroenterol, 2012, 18(2): 119
[13] 邢伟，孔维涵，方步武．蒿鳖养阴软坚方对免疫性肝纤维化大鼠的治疗作用[J]．中草药，2010，10（41）：1667
[14] 寇咏梅，刘洁莹，方步武．蒿鳖养阴软坚方抗小鼠血吸虫病肝纤维化及其机制的研究[J]．现代药物与临床，2013，3（28）：288
[15] 赵敏，郭娟，方步武，等．蒿鳖养阴软坚方对大鼠酒精性肝损伤的预防作用[J]．时珍国医国药，2010，11（21）：2887
[16] 杨凤蕊，娄建石，方步武．蒿鳖养阴软坚方抗CCl4复合因素所致大鼠肝纤维化的作用[J]．中草药，2011，3（42）：530

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备注/Memo

备注/Memo:

文章编号 １００６－８１４７（２０18）０2-0112-04
作者简介 卢娜（1992-），女，硕士在读，研究方向：中药药理；通信作者：方步武，E-mail：fangdch@aliyun.com。

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更新日期/Last Update: 2018-03-20