丹芍化纤胶囊对基质金属蛋白酶-1表达的影响Effects of Danshaohuaxian Capsules on Expression of MMP-1 in Rat Hepatic Fibrosis
谢汝佳,杨勤,罗新华,耿晓霞,韩冰,李诚秀,程明亮
XIE Ru-jia 1; YANG Qin 1; LUO Xin-hua 2; GENG Xiao-xia 3; HAN Bing 1; LI Cheng-xiu 4; CHENG Ming-liang 3 (1. Department of Pathophysiology;
摘要(Abstract):
目的 :探讨丹芍化纤胶囊抗大鼠肝纤维化的作用及对基质金属蛋白酶 1(MMP 1)表达的影响。方法 :雄性Wistar大鼠 80只分为正常组、肝纤维化模型组、自然恢复组、低剂量治疗组、高剂量治疗组 ,除正常组外 ,其余采用四氯化碳 (CCl4)、饮酒、高脂低蛋白饮食等复合病因刺激制备肝纤维化动物模型 8周 ,然后两治疗组分别予以低剂量 (0 5g/kg)、高剂量 (1g/kg)丹芍化纤胶囊灌胃 8周。实验结束后测定肝脏指数、血清透明质酸(HA)及谷丙转氨酶 (ALT) ,光镜下观察肝组织纤维化程度 ,检测尿羟脯氨酸 (Hyp)排出量 ,同时免疫组织化学SABC法检测肝组织MMP 1的表达。结果 :治疗组与肝纤维化模型组及自然恢复组比较 ,肝脏指数、血清HA及ALT显著下降 ,肝纤维化程度显著减轻 ,尿Hyp排出明显增加 ,肝脏MMP 1表达显著增加。以上结果均以高剂量组较低剂量组改善明显。结论 :丹芍化纤胶囊增加大鼠肝组织中MMP 1的表达 ,可能是其抗纤维化作用的机制之一。
Objective: To investigate the effects of Danshaohuacian (DSHX) capsules which is based on traditional Chinese medicine prescription, on the expression of MMP-1 in rat hepatic fibrosis.Methods: 80 male Wistar rats were randomly divided into normal control group (CG), CCl 4-induced hepatic fibrosis group (CIG), non-DSHX-treated group (NDG), low-dose-treated group (LDG) and high-dose-treated group (HDG). Except for the normal control group, the rats were subcutaneously injected with CCl 4, given alcohol drinking, diet with high lipid and low protein for 8 weeks to produce hepatic fibrotic models. Then, rats in groups LDG and HDG were treated respectively with low dose (0.5 g/kg) and high dose (1.0 g/kg) of DSHX capsule by p.o everyday for 8 weeks. At the end of the experiment, the liver indexes were calculated; the serum hyaluronic acid (HA) and alanine aminotransferase (ALT) were examined; the degree of hepatic fibrosis were evaluated with optical microscopy; the urinary excretion of hydroxyproline (Hyp) was determined; the expression of collagen type I, III were detected with immunohistochemical techniques.Results: Compared with the indexes of hepatic fibrosis group and non-DSHX-treated group, it was revealed that in the two treated groups: the liver indexs, levels of serum HA and ALT and stage of hepatic fibrosis were all significantly reduced; the urinary excretion of Hyp increased; the expression of MMP-1 in liver tissues increased. All these alterations in HDG group were more obvious than those in LDG group,but no difference was found.Conclusion: The DSHX capsule could enhance the expression of MMP-1 in the liver tissues of CCl 4-induced hepatic fibrosis rats, which might be related with its anti-hepatic fibrosis activity.
关键词(KeyWords):
四氯化碳;肝硬化;间质胶原酶;羟脯氨酸;大鼠;丹芍化纤胶囊
carbon tetrachloride; liver cirrhosis; interstitial collagenase; hydroxyproline; rats; Danshaohuaxian capsule
基金项目(Foundation): 贵州省特殊人才基金资助( 2 0 0 3 1 )
作者(Authors):
谢汝佳,杨勤,罗新华,耿晓霞,韩冰,李诚秀,程明亮
XIE Ru-jia 1; YANG Qin 1; LUO Xin-hua 2; GENG Xiao-xia 3; HAN Bing 1; LI Cheng-xiu 4; CHENG Ming-liang 3 (1. Department of Pathophysiology;
DOI: 10.19367/j.cnki.1000-2707.2004.05.006
参考文献(References):
- [1]杨长青,胡国龄,谭德明,等.实验性肝纤维化时MMP 1、TIMP 1的表达与Ⅰ、Ⅲ型胶原含量变化的关系[J].临床肝胆杂志,2002,16(4):222-224.
- [2]程明亮,杨长青.肝纤维化的基础研究及临床[M].第2版.北京:人民卫生出版社,2002.20-35.
- [3]王志荣,陈锡美,李定国,等.联合应用粉防己碱与甘草酸抑制肝纤维化大鼠细胞外基质表达[J].世界华人消化杂志,2003,11(7):970-974.
- [4]IasoE ,FriedmanSL .Molecularregulationofhepaticfibrogen esis[J].JHepatol,1998,29(5):836.
- [5]孟二红,赵景民,王松山,等.基质金属蛋白酶在非酒精性脂肪性肝炎患者肝组织中的表达[J].世界华人消化杂志,2002,10(11):1257-1260.
- [6]彭慧,汪谦,黄洁夫.人Ⅰ型基质金属蛋白酶基因真核表达重组质粒的构建[J].中山医科大学学报,2001,22(6):433-435,453.
- [7]周光德,赵景民,王松山,等.酒精性肝纤维化基质降解机制的研究[J].解放军医学杂志,2002,27(4):343-345.
- [8]杨长青,王吉耀,郭津生,等.大鼠基质金属蛋白酶1表达质粒对实验性肝纤维化的影响[J].中华消化杂志,2000,20(5):297-300.
- [9]IredaleJP ,BenyonRC ,ArthuyMJP ,etal.Tissueinhabitorofmetalloproteinase1messengerRNAexpressionisenhancedrelativetointerstitialcollagenasemessengerRNAinexperi mentalliverinjuryandfibrosis[J].Hepatology,1996,24(1):176.
- [10]黄宇琦,高毅,陈泽洪,等.间质胶原酶及其抑制因子1不平衡表达与肝纤维化的关系[J].第一军医大学学报,1999,19(3):208-210.
文章评论(Comment):
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- 四氯化碳
- 肝硬化
- 间质胶原酶
- 羟脯氨酸
- 大鼠
- 丹芍化纤胶囊
carbon tetrachloride - liver cirrhosis
- interstitial collagenase
- hydroxyproline
- rats
- Danshaohuaxian capsule
- 谢汝佳
- 杨勤
- 罗新华
- 耿晓霞
- 韩冰
- 李诚秀
- 程明亮
XIE Ru-jia 1 - YANG Qin 1
- LUO Xin-hua 2
- GENG Xiao-xia 3
- HAN Bing 1
- LI Cheng-xiu 4
- CHENG Ming-liang 3 (1. Department of Pathophysiology
- 谢汝佳
- 杨勤
- 罗新华
- 耿晓霞
- 韩冰
- 李诚秀
- 程明亮
XIE Ru-jia 1 - YANG Qin 1
- LUO Xin-hua 2
- GENG Xiao-xia 3
- HAN Bing 1
- LI Cheng-xiu 4
- CHENG Ming-liang 3 (1. Department of Pathophysiology