苦参素对实验性肝纤维化的防治作用及对MMP-2 表达的影响

中国临床药理学与治疗学 ›› 2004, Vol. 9 ›› Issue (10): 1096-1100.

苦参素对实验性肝纤维化的防治作用及对MMP-2 表达的影响

周爱玲^1,2, 罗琳¹, 茅家慧², 朱燕²

¹南通大学基础医学院药理学教研室,²病理生理学教研室, 南通226001, 江苏

收稿日期:2004-07-21 修回日期:2004-09-09 出版日期:2004-10-26 发布日期:2020-11-23
通讯作者: 周爱玲, 女, 教授, 硕士生导师, 研究方向:消化病理生理与消化系统药理。Tel:0513-5051732 E-mail:ai lingzhou0513 @163. com
基金资助:
江苏省教育厅资助课题(№01KJB360003)

Effects of kwoninone on experimental liver fibrosis and expression of matrix metalloproteinase-2 in rats

ZHOU Ai-Ling^1,2, LUO Lin¹, MAO Jia-Hui², ZHU Yan²

¹Department of Pharmacology,²Department of Pathophysiology, Medical College of Nantong University, Nantong 226001, Jiangsu, China

Received:2004-07-21 Revised:2004-09-09 Online:2004-10-26 Published:2020-11-23

摘要/Abstract

摘要： 目的: 观察苦参素预防及治疗大鼠肝纤维化的疗效并探讨其作用机制。方法: 采用CCl₄ 诱导大鼠肝纤维化模型, SD 大鼠28 只, 随机分为4 组:正常对照组、模型对照组、苦参素预防组、苦参素治疗组。实验10 周末, 测定血清丙氨酸氨基转移酶(ALT) 、天冬氨酸氨基转移酶(AST) 、总胆汁酸(TBA)及谷氨酸转移酶(GGT); 光镜、电镜观察肝细胞结构和肝纤维化程度;RT-PCR 和蛋白酶谱法检测肝组织中MMP-2 mRNA 、MMP-2 蛋白的表达。结果: 苦参素预防与治疗给药均能明显降低CCl₄ 诱导的肝纤维化大鼠血清ALT 、AST 、TBA 及GGT 水平(P<0. 05,P<0. 01) 。苦参素预防组、治疗组大鼠胶原纤维沉积明显减轻, 假小叶结构明显减少。苦参素预防组、治疗组肝细胞结构接近正常, Disse 间隙、肝细胞内胶原纤维明显减少, 且苦参素预防组肝纤维化程度轻于治疗组。苦参素预防组、治疗组肝组织中MMP-2mRNA 、MMP-2 活性蛋白的表达显著低于模型组(P<0. 05, P<0. 01) 。结论: 苦参素对CCl₄ 诱导的肝纤维化有预防及治疗作用, 其部分机制为通过减少MMP-2mRNA 、MMP-2 活性蛋白的表达, 促进细胞外基质(ECM) 的降解, 抑制ECM 沉积, 从而减轻或逆转肝纤维化。

关键词: 苦参素, 四氯化碳, 肝纤维化, 逆转录聚合酶链反应, 基质金属蛋白酶-2, 细胞外基质

Abstract: AIM: To investigate the prophylactic and therapeutic effects and mechanisms of kwoninone in rats with experimental liver fibrosis.METHODS: The animal models with liver fibrosis were prepared in rats by administration of carbon tetrachloride (CCl₄ ). 28 SD rats were randomly divided into 4 groups: normal control group, model control group, kwoninone prophylactic group and kwoninone therapeutic group. After 10 weeks of administration, the levels of ALT, AST, TBA and GGT were measured in rat serum. The histopathological changes were observed by light microscopy and electromicroscopy. The expressions of matrix metalloproteinase-2 (MMP-2) mRNA in liver were detected by reverse transcription polymerase chain reaction. The expressions of proteins of MMP-2 in liver were determined by gelatin zymography.RESULTS: The serum levels of ALT, AST, TBA and GGT in liver fibrosis rats were decreased in the kwoninone prophylactic groups and therapeutic groups(P<0. 05, or P<0. 01). The levels of fibrogenesis in liver tissues were more significantly decreased in the kwoninone prophylactic groups and therapeutic groups than that in the model control groups. The formations of liver pseudoluboli were alleviated in the kwoninone prophylactic groups and therapeutic groups. Structures of liver cells were recovered and few collagenous fibers were found in Disse space in the kwoninone prophylactic groups and therapeutic groups. The levels of the liver fibrosis in kwoninone prophylactic group were lighter than that in the therapeutic groups.The levels of MMP-2 mRNA and proteins of MMP-2 in the liver significantly decreased in the kwoninone prophylactic groups and therapeutic groups.CONCLUSION: Kwoninone can protect and therapy liver fibrosis induced by CCl₄ in rats, down-regulate the expression of MMP-2mRNA and proteins of MMP-2 levels, accelerate the degradation of ECM, and inhibit the deposition of the ECM in liver.

Key words: kwoninone, carbon tetrachloride, liver fibrosis, reverse transcription polymerase chain reaction, matrix metalloproteinase-2, extracellular matrix, rats

中图分类号:

R285
R575.2

周爱玲, 罗琳, 茅家慧, 朱燕. 苦参素对实验性肝纤维化的防治作用及对MMP-2 表达的影响[J]. 中国临床药理学与治疗学, 2004, 9(10): 1096-1100.

ZHOU Ai-Ling, LUO Lin, MAO Jia-Hui, ZHU Yan. Effects of kwoninone on experimental liver fibrosis and expression of matrix metalloproteinase-2 in rats[J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2004, 9(10): 1096-1100.

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