[1]黄小华,孙 永,沈 能,等.双亲姜黄素衍生物减轻大鼠肝纤维化与抗炎抗氧化作用的研究[J].中国药理学通报,2015,(04):470-474.
 HUANG Xiao-hua,SUN Yong,SHEN Neng,et al.The amphiphilic curcumin derivative attenuates liver fibrosis by anti-inflammatory and antioxidant effect[J].Chinese Pharmacological Bulletin,2015,(04):470-474.
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双亲姜黄素衍生物减轻大鼠肝纤维化与抗炎抗氧化作用的研究()
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《中国药理学通报》[ISSN:/CN:]

卷:
期数:
2015年04期
页码:
470-474
栏目:
论 著
出版日期:
2015-04-25

文章信息/Info

Title:
The amphiphilic curcumin derivative attenuates liver fibrosis by anti-inflammatory and antioxidant effect
作者:
黄小华1 孙 永1沈 能2唐华东3任 红1彭明利1
1.重庆医科大学感染性疾病分子生物学教育部重点实验室,重庆 400010; 2.重庆市肿瘤医院,重庆 400030; 3.浙江工业大学,浙江 杭州 310014
Author(s):
HUANG Xiao-hua1 SUN Yong1 SHEN Neng2 TANG Hua-dong3 REN Hong1 PENG Ming-li1
1.Key Laboratory of Molecular Biology of Infectious Disease, Chongqing University of Medical Science, Chongqing 400010,China; 2.Chongqing Cancer Institute, Chongqing 400030,China; 3、Zhejiang University of Technology, Hangzhou 310014,China
关键词:
姜黄素 灌胃治疗 衍生物 静脉注射 纤维化 抗炎 抗氧化
Keywords:
curcumin intragastric administration derivative intravenous fibrosis anti-inflammatory antioxidant
分类号:
R-332; R284.1; R322.47; R329.24; R452; R575.205.31
文献标志码:
A
摘要:
目的 探讨新型双亲姜黄素衍生物(curc-OEG)对四氯化碳(CCl4)诱导大鼠肝纤维化的抗炎抗氧化作用。方法 大鼠分为正常组、模型组、姜黄素组和姜黄素衍生物组。除正常组外,其余各组给予CCl4混合液皮下注射,每周2次。造模4周后,正常组、模型组给与尾静脉注射生理盐水,姜黄素组给予姜黄素400 mg·kg-1·d-1灌胃治疗,姜黄素衍生物组给予姜黄素衍生物100 mg·kg-1·d-1尾静脉注射。治疗4周后分别取血清及肝组织标本。血清检测ALT、AST水平; 肝组织做病理学检查,Real-time PCR法检测相关炎症因子的mRNA表达水平,试剂盒检测丙二醛(MDA)、超氧化物歧化酶(SOD)、谷胱甘肽(GSH)水平。结果 正常组、模型组、姜黄素组和姜黄素衍生物组ALT水平分别为:(31.7±8.7)U·L-1、(383.0±75.6)U·L-1、(406.3±204.7)U·L-1、(107.0±73.7)U·L-1; AST水平分别为:(137.7±32.7)U·L-1、(585.3±36.7)U·L-1、(485.0±246.5)U·L-1、(202.7±56.0)U·L-1,姜黄素衍生物较姜黄素显示出更好的护肝降酶作用(P<0.05)。肝脏病理切片显示姜黄素衍生物较姜黄素具有更明显的延缓肝脏脂肪变性、减轻炎症细胞浸润及抗肝纤维化的作用。与姜黄素比较,姜黄素衍生物明显下调炎症相关因子NF-κB、IL-1β、IL-6、TNF-α、COX-2mRNA及蛋白表达水平(P<0.05); 明显降低肝组织中MDA水平,提高GSH 、SOD表达水平,增强抗氧化能力。结论 姜黄素衍生物较传统姜黄素具有更好的抗炎、抗氧化作用,能够有效地延缓四氯化碳诱导的肝纤维化进程。
Abstract:
Aim To investigate the effects of anti-in-flammation and antioxidation of an amphiphilic curcu-min derivative(Curc-OEG)on CCl4-induced hepatic fibrosis in rats. Methods Rats were randomly divided into four groups: control group,model group,curcumin and Curc-OEG treatment group. All rats except those in control group were given subcutaneous injection of CCl4 and olive oil mixture, twice a week for 8 weeks. After 4 weeks, rats of control and model group were treated with normal saline intravenously, curcumin group were administered with curcumin 400 mg.kg-1.d-1 by gavage and Curc-OEG group were treated with Curc-OEG 100 mg.kg-1.d-1 intravenously respectively. After 4 weeks treatment, the serum levels of ALT and AST were tested. HE and Sirus staining were used to evaluate the extent of liver inflammation and fibrosis. The mRNA expression levels of proinflammatory cytokines of NF-kB, IL-1β, IL-6, TNF-α, COX-2 were observed with Real Time PCR. The level of MOD, SOD and GSH in liver of rats were quantified. Results The levels of ALT in control, model, curcumin and Curc-OEG group was(31.7±8.7)U·L-1,(383.0±75.6)U·L-1,(406.3±204.7)U·L-1,(107.0±73.7)U·L-1 respectively; that of AST was(137.7±32.7)U·L-1,(585.3±36.7)U·L-1,(485.0±246.5)U·L-1,(202.7±56.0)U·L-1 respectively, Curc-OEG possessed more hepatoprotective effects than that of curcumin. Liver pathology showed Curc-OEG treatment could significantly alleviate steatosis, reduce inflammation and apparently suppress hepatic fibrogenesis by reducing the thickness of bridging fibrotic septa. Compared with curcumin, Curc-OEG down-regulated mRNA and protein expression levels of NF-kB, IL-1β, IL-6, TNF-α, COX-2(P<0.05). Moreover, Curc-OEG reduced the level of MOD and increased the levels of SOD and GSH. Conclusion Curc-OEG could more significantly protect the rat liver from CCl4 -caused fibrogenesis by anti-inflammatory and antioxidant effect than curcumin.

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备注/Memo

备注/Memo:
收稿日期:2014-12-05,修回日期:2015-01-15 基金项目:国家自然科学基金资助项目(No 30771921) 作者简介:黄小华(1987-),女,硕士生,研究方向:肝纤维化的药物研究,E-mail:huangxianiboy@163.com; 彭明利(1972-),女,副研究员,硕士生导师,研究方向:肝纤维化发病机制与药物开发,通讯作者,E-mail:pengmingli@cqmu.edu.cn
更新日期/Last Update: 1900-01-01