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[1]柴宁莉,徐世平,石卉,等.精氨酸-甘氨酸-天冬氨酸对氧化苦参碱脂质体减轻肝纤维化的增强作用研究[J].环球中医药,2012,5(09):645-0.
　CHAI Ning li,X Shi ping,SHI Hui,et al.ArginineGlycinAspartic acid could enhance oxymatrine liposomes theraputic effect on hepatic fibrosis[J].,2012,5(09):645-0.
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精氨酸-甘氨酸-天冬氨酸对氧化苦参碱脂质体减轻肝纤维化的增强作用研究()
     
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《环球中医药》[ISSN:1006-6977/CN:61-1281/TN]

卷:
第5卷
期数:
2012年09期
页码:
645-0
栏目:
论著
出版日期:
2012-09-06

文章信息/Info

Title:
ArginineGlycinAspartic acid could enhance oxymatrine liposomes theraputic effect on hepatic fibrosis
作者:
柴宁莉; 徐世平; 石卉; 常青; 赵擎; 万军; 蔡昌豪; 吴本俨;
Author(s):
CHAI Ningli;  X Shiping;  SHI Hui;  et al.
Department of Gastroenterology, South Building of Chinese PLA General Hospital, Beijing 100853, China
关键词:
氧化苦参碱脂质体;  肝纤维化;  精氨酸-甘氨酸-天冬氨酸
Keywords:
Oxymatrine liposomes; Hepatic fibrosis; ArginineGlycinAspartic
分类号:
R285.5
DOI:
-
文献标志码:
A
摘要:
目的探讨精氨酸-甘氨酸-天冬氨酸(Arginine-Glycin-Aspartic acid,RGD)三肽序列对氧化苦参碱脂质体(oxymatrine liposomes,OXYL)治疗四氯化碳诱导的肝纤维化(hepatic fibrosis,HF)作用的影响。方法建立四氯化碳诱导的大鼠HF模型,制备RGD-OXYL和OXYL。动物分组为:正常对照组; 肝纤维化模型组; OXYL治疗组; RGD-OXYL治疗组; RGD脂质体组。检测各组大鼠血清ALP,利用HE染色和Masson染色评价肝脏病理损伤及细胞外基质沉积情况。分离各组大鼠的肝脏组织,利用半定量PCR检测纤维化相关基因(TIMP-1,MMP-2)表达。结果成功合成OX-YL及RGD-OXYL。与肝纤维化组比较,OXYL治疗组大鼠的ALP水平下降(344.47±27.52vs550.69±43.78,P<0.05)、肝损伤减轻、细胞外基质沉积面积显著减少(2.36%±0.09%vs7.70%±0.60%,P<0.05)、纤维化相关基因(TIMP-1,MMP-2)表达下调; 与OXYL治疗组大鼠相比,RGD-OX-YL治疗组大鼠ALP水平(272.51±19.55vs344.47±27.52,P<0.05)和肝损伤及细胞外基质沉积面积(0.26%±0.09%vs2.36%±0.09%,P<0.05)及纤维化相关基因(TIMP-1,MMP-2)表达等指标均有均有进一步改善。结论氧化苦参碱脂质体可减轻四氯化碳诱导的肝纤维化,抑制纤维化相关基因表达。RGD偶联的OXYL治疗效果优于OXYL。
Abstract:
ObjectiveTo investigate whether ArginineGlycinAspartic acid (RGD) could enhance Oxymatrine liposomes (OXYL) theraputic effect on CCl4 induced hepatic fibrosis in rat. MethodsCCl4induced hepatic fibrosis model was constructed based on rats. Different formulations of oxymatrine were established in this study, i.e. RGDOXYL and OXYL. Animals were diveded into five groups, which was control group, CCl4induced hepatic fibrosis group, OXYL group, RGDOXYL group and RGDLiposomes control group. To evaluate the antifibrotic effect, levels of alkaline phosphatase, hepatic histopathology (HE and Masson staining) were detected. Moreover,fibrosisrelated gene expression of matrix metallopeptidase2 (MMP2), tissue inhibitor of metalloproteinases1 (TIMP1) were determined via semiquantitative polymerase chain reaction. ResultsOxymatrine can attenuate CCl4induced hepatic fibrosis, as defined by reducing serum alkaline phosphatase (344.47±27.52 vs 550.69±43.78, P<005), attenuating liver injury and improving collagen deposits (2.36%±0.09% vs 7.70%±0.60%, P<0.05) and down regulating fibrosisrelated gene expression, i.e., MMP2, TIMP1 (P<005). RGD could enhance the therapeutic effect of OM in terms of serum alkaline phosphatase (272.51±19.55 vs 34447±27.52, P< 0.05), liver injury, collagen deposits (0.26%±0.09% vs 2.36%±009%, P< 005) and down regulating fibrosisrelated gene expression, i.e., MMP2, TIMP1 (P<005).ConclusionOXYL could attenuate CCL4induced hepatic fibrosis and inhibit fibrosisrelated gene expression. RGD could enhance theraputic effect. of OXYL.

参考文献/References:

[1]Wu XN, Wang GJ.Experimental studies of oxymatrine and its mechanisms of action in hepatitis B and C viral infections[J]. Chin J Dig Dis, 2004，5(1)：1216.
[2]Stern MM, Myers RL, Hammam N, et al. The influence of extracellular matrix derived from skeletal muscle tissue on the proliferation and differentiation of myogenic progenitor cells ex vivo[J]. Biomaterials，2009，30(12)：23932399.
[3]Friedman, SL.Molecular regulation of hepatic fibrosis, an integrated cellular response to tissue injury[J]. J Biol Chem，2000，275(4)：22472250.
[4]Xu WS, Zhao KK, Miao XH,et al. Effect of oxymatrine on the replication cycle of hepatitis B virus in vitro[J]. World J Gastroenterol，2010，16(16)：20282037.
[5]杜施霖,王吉耀,陆伟跃，等.含有精甘天冬氨酸序列的环肽与大鼠肝星状细胞体外结合的特性[J].中华肝脏病杂志,2005,13(5):362365.
[6]Wang XB, Liu P, Tang ZP, et al. The role of changes of MMP2, 9 activity in the development of liver fibrosis in rats[J]. Zhonghua Gan Zang Bing Za Zhi, 2004，12(5)：267270.
[7]Rossi L, Ergen AV, Goodell MA. TIMP1 deficiency subverts cellcycle dynamics in murine longterm HSCs[J]. Blood，2011，117(24)：64796488.
[8]Schiffelers RM, Koning GA, ten Hagen TL,et al. Antitumor efficacy of tumor vasculaturetargeted liposomal doxorubicin[J]. J Control Release，2003，91(12):115122.
[9]Janssen AP, Schiffelers RM, ten Hagen TL, et al. Peptidetargeted PEGliposomes in antiangiogenic therapy[J]. Int J Pharm，2003，254(1)：5558.

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备注/Memo

备注/Memo:
基金项目：国家自然科学基金（30600848）
作者单位：100853 北京，中国人民解放军总医院南楼消化内科
作者简介：柴宁莉（1972- ），博士，副主任医师，中华医学会消化内镜分会青年委员。研究方向：肝胆疾病相关基础及临床研究。 Email：csxlily@163.com
更新日期/Last Update: 1900-01-01