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[三七总皂苷对肝纤维化大鼠基质金属蛋白酶-13和基质金属蛋白酶组织抑制因子-1表达的影响]

[Effect of Panax notoginseng saponins on expressions of MMP-13 and TIMP-1 in rats with hepatic fibrosis].

作者信息

Jiang Hui, Xia Lun-Zhu, Li Ying, Li Xiang, Wu Jian

机构信息

The First Affiliated Hospital of Anhui University of Traditional Chinese Medicine, Grade Three Laboratory of Traditional Chinese Medicine Preparations under State Administration of Traditional Chinese Medicine, Hefei 230031, China.

出版信息

Zhongguo Zhong Yao Za Zhi. 2013 Apr;38(8):1206-10.

Abstract

OBJECTIVE

To investigate the effect of Panax notoginseng saponins (PNS) on the expressions of matrix metalloproteinase (MMP)-13 and its tissue inhibitor of metalloproteinase (TIMP)-1 in carbon tetrachloride (CCl4)-induced hepatic fibrosis rats, and explore the possible mechanism of PNS's effect against hepatic fibrosis.

METHOD

The rats were randomly divided into 6 groups: the normal group, the model group, PNS (50, 100, 200 mg x kg(-1)) treatment groups and the Col (0.1 mg x kg(-1)) group. Apart from the normal group, all of the remaining groups were subcutaneously injected with CCl4 twice a week for 18 weeks, in order to establish the hepatic fibrosis rat model. Since the 9th weeks, each treatment group was orally administered with corresponding drugs, and the normal group and the model group were orally administered with equal volume of normal saline for 10 weeks. After the end of the experiment, liver and spleen indexes were calculated; the levels of serum ALT and AST were measured by chromatometry. Liver tissues were collected to detect the pathological alteration HE staining; protein expressions of MMP-13 and TIMP-1 were determined with immuninochemistry. Moreover, MMP-13 and TIMP-1 mRNA expressions was detected by RT-PCR technology.

RESULT

Compared with the model group, PNS (100, 200 mg x kg(-1)) significantly mitigated hepatic fibrosis in rats, reduced liver and spleen indexes, ALT and AST contents in serum, and TIMP-1 expression, and notably increased MMP-13 expression in rats with hepatic fibrosis.

CONCLUSION

P. notoginseng saponins have certain protective effect in rats with hepatic fibrosis. Its mechanism is related to up-regulating MMP-3, inhibiting TIMP-1 expression and improving collagen degradation.

摘要

目的

研究三七总皂苷(PNS)对四氯化碳(CCl4)诱导的肝纤维化大鼠基质金属蛋白酶(MMP)-13及其金属蛋白酶组织抑制剂(TIMP)-1表达的影响,探讨PNS抗肝纤维化的可能机制。

方法

将大鼠随机分为6组:正常组、模型组、PNS(50、100、200mg·kg-1)治疗组和秋水仙碱(0.1mg·kg-1)组。除正常组外,其余各组每周皮下注射CCl4 2次,共18周,以建立肝纤维化大鼠模型。自第9周起,各治疗组灌胃相应药物,正常组和模型组灌胃等体积生理盐水,共10周。实验结束后,计算肝脾指数;采用比色法测定血清ALT和AST水平。取肝组织进行HE染色观察病理改变;采用免疫组化法检测MMP-13和TIMP-1蛋白表达。此外,采用RT-PCR技术检测MMP-13和TIMP-1 mRNA表达。

结果

与模型组相比,PNS(100、200mg·kg-1)能显著减轻大鼠肝纤维化程度,降低肝脾指数、血清ALT和AST含量以及TIMP-1表达,显著增加肝纤维化大鼠MMP-13表达。

结论

三七总皂苷对肝纤维化大鼠有一定的保护作用。其机制与上调MMP-3、抑制TIMP-1表达及促进胶原降解有关。

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