姜黄素衍生物对四氯化碳诱导肝纤维化的治疗作用

中国临床药理学与治疗学 ›› 2012, Vol. 17 ›› Issue (2): 147-153.

姜黄素衍生物对四氯化碳诱导肝纤维化的治疗作用

邓燕红¹, 沈能¹, 凌宁², 胡鹏², 任红^1,2, 唐华东³, 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,
²重庆医科大学附属第二医院感染科,重庆 400010;
³浙江工业大学,杭州 310023,浙江

收稿日期:2011-11-01 修回日期:2011-11-08 出版日期:2012-02-26 发布日期:2012-03-12
通讯作者: 彭明利,女,博士,副研究员,硕士生导师,研究方向:乙型肝炎及肝纤维化机理研究。E-mail: minglip55@yahoo.com.cn
作者简介:邓燕红,女,硕士在读,研究方向:肝纤维化药物研究。Tel: 13752814239 E-mail: dengyh1986@163.com
基金资助:
国家自然科学基金资助项目(30771921)

Efficacy of the Gurc-OEG on rat liver fibrosis induced by CCl₄

DENG Yan-hong¹, SHEN Neng¹, LING Ning², HU Peng², REN Hong^1,2, TANG Hua-dong³, PENG Ming-li¹

¹Key Laboratory of Molecular Biology of Infectious Disease, Chongqing University of Medical Science;
²Division of Infectious Diseases of the Second Affiliated Hospital of Chongqing Medical University,Chongqing 400010,China;
³Zhejiang University of Technology,Hangzhou 310023, Zhejiang, China

Received:2011-11-01 Revised:2011-11-08 Online:2012-02-26 Published:2012-03-12

摘要/Abstract

摘要： 目的: 探讨姜黄素衍生物(Curc-OEG)对四氯化碳诱导肝纤维化的治疗效果。方法: 以四氯化碳诱导形成大鼠肝实质损伤性肝纤维化模型。大鼠分为正常对照组(A组)、模型组(B组)、低剂量组(C组)、中剂量组(D组)、高剂量组(E组)、秋水仙碱组(F组)。除A组外,各组给予四氯化碳和橄榄油混合液皮下注射,2次/周,4周后B组给予生理盐水尾静脉注射,C、D、E组分别给予25、50、100 mg·kg^-1·d^-1的Curc-OEG尾静脉注射,F组给予0.1 mg·kg^-1·d^-1秋水仙碱灌胃。10周后测定肝功能及肝组织羟脯氨酸(Hyp)含量;做肝脏HE和天狼星红染色;定量PCR法测金属蛋白酶抑制因子-1(TIMP-1)、金属蛋白酶-13(MMP-13)基因的表达,Western Blot法测CollagenⅠ蛋白的表达。结果: 与模型组比较,中、高剂量组ALT、AST明显降低(P<0.05),羟脯氨酸及CollagenⅠ蛋白表达明显降低(P<0.05),MMP-13 mRNA明显上调(P<0.05),以及TIMP-1 mRNA明显下调(P<0.05),并且HE及天狼星红染色结果也观察到肝脏炎症及纤维化程度明显减轻。结论: Curc-OEG能减轻四氯化碳诱导的大鼠肝纤维化。

关键词: 肝纤维化, 姜黄素, 金属蛋白酶-13, 金属蛋白酶抑制因子-1

Abstract: AIM: To evaluate the efficacy of Curc-OEG in preventing CCl₄-induced hepatic fibrosis and to study the effects of that on expression of MMP-13 mRNA,TIMP-1 mRNA and CollagenⅠ.METHODS: Liver fibrosis in rats was induced by CCl₄. Rats were assigned into control group(A),model group(B),low-dose group(C),medium-dose group(D), high-dose group(E) and colchicin group(F).All rats except those in group A were given subcutaneous injection of CCl₄ and olive oil mixture,twice a week for 10 weeks. After 4 weeks, those in group B were treated with normal saline by intravenous injection,those in group C,D and E were treated with Curc-OEG for 25,50,100 mg·kg^-1·d^-1 by intravenous injection, those in group F were treated with colchicin for 0.1 mg·kg^-1·d^-1 by gavage as positive control.At the end of the tenth week, the serum levels of ALT, AST and cotent of hydroxyproline in homogenate were determined. The extent of liver inflammation and fibrosis was evaluated with HE and Sirus staining. The expressions of MMP-13,TIMP-1 and CollagenⅠwere observed with RT-PCR and Western Blot respectively.RESULTS: Compared with model group,medium and high dose of curcumin derivative could obviously decrease the content of hydroxyproline in liver tissue(P<0.05) and levels of ALT, AST in serum(P<0.05) and expression of CollagenⅠ(P<0.05), and it also reduced inflammation destruction of liver architecture and collagen accumulation. Further study showed that MMP-13 mRNA was up-regulated(P<0.05) and TIMP-1 mRNA was down-regulated(P<0.05) after Curc-OEG treatment.CONCLUSION: Curc-OEG could ameliorate the progress of liver fibrosis induced by CCl₄.

Key words: Hepatic fibrosis, Curcumin, Matrix metalloproteinase-13, Tissue inhibitor of metalloproteinase-1

中图分类号:

R965.2

邓燕红, 沈能, 凌宁, 胡鹏, 任红, 唐华东, 彭明利. 姜黄素衍生物对四氯化碳诱导肝纤维化的治疗作用[J]. 中国临床药理学与治疗学, 2012, 17(2): 147-153.

DENG Yan-hong, SHEN Neng, LING Ning, HU Peng, REN Hong, TANG Hua-dong, PENG Ming-li. Efficacy of the Gurc-OEG on rat liver fibrosis induced by CCl₄[J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2012, 17(2): 147-153.

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