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连翘水提物对四氯化碳致小鼠肝纤维化的保护作用。

Hepatoprotective effect of Forsythiae Fructus water extract against carbon tetrachloride-induced liver fibrosis in mice.

机构信息

The MOE Key Laboratory for Standardization of Chinese Medicines, Shanghai Key Laboratory of Compound Chinese Medicines and The SATCM Key Laboratory for New Resources and Quality Evaluation of Chinese Medicines, Institute of Chinese Materia Medica, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China.

Center for Drug Safety Evaluation and Research, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China.

出版信息

J Ethnopharmacol. 2018 May 23;218:27-34. doi: 10.1016/j.jep.2018.02.033. Epub 2018 Feb 20.

DOI:10.1016/j.jep.2018.02.033
PMID:29474900
Abstract

ETHNOPHARMACOLOGICAL RELEVANCE

The fruit of Forsythia suspensa (Thunb.) Vahl, named Forsythiae Fructus (Lian-Qiao), is a well-known traditional Chinese medicine (TCM) used for clearing away heat and toxic material, eliminating the mass and relieving swelling.

AIM OF THE STUDY

This study aims to observe the attenuation of the water extract of Forsythiae Fructus (FSE) on carbon tetrachloride (CCl)-induced hepatic fibrosis in male C57BL/6 mice.

MATERIALS AND METHODS

Hepatic fibrosis was induced in male C57BL/6 mice by intraperitoneal injection with 2 ml/kg CCl (mixed 1: 3 in olive oil) twice a week for 4 weeks. At the same time, the mice were orally given with FSE (1, 2 g/kg) every day for 4 weeks. Serum biochemical parameters, gene and protein expression related to liver fibrosis were analyzed. The contents of forsythiaside A and forsythin in FSE were measured by high-performance liquid chromatography (HPLC).

RESULTS

Results of serum alanine/aspartate aminotransferase (ALT/AST) activity and liver histological evaluation both showed the protection of FSE against CCl-induced liver injury. Further, the anti-fibrotic effects of FSE was evidenced by the results of Masson's trichrome and Sirius red staining, liver hydroxyproline content, and serum amounts of hyaluronic acid, laminin, collagen Ⅳ and type III procollagen (PCIII). FSE also reduced the expression of α-smooth muscle actin (α-SMA) in livers from CCl-injured mice. Additionally, FSE decreased the increased hepatic expression of fibroblast-specific protein 1 (FSP1) and vimentin induced by CCl in mice.

CONCLUSIONS

FSE attenuates CCl-induced liver fibrosis in mice by inhibiting hepatic stellate cells (HSCs) activation, reducing hepatic extracellular matrix (ECM) disposition and reversing epithelial-mesenchymal transition (EMT).

摘要

药草学相关性

连翘的果实,被称为连翘果实(连桥),是一种著名的中药,用于清热、解毒、消肿。

研究目的

本研究旨在观察连翘水提取物(FSE)对雄性 C57BL/6 小鼠四氯化碳(CCl)诱导的肝纤维化的衰减作用。

材料与方法

雄性 C57BL/6 小鼠通过腹腔注射 2ml/kg CCl(橄榄油混合 1:3)每周两次,共 4 周,诱导肝纤维化。同时,小鼠每天口服 FSE(1、2g/kg)4 周。分析与肝纤维化相关的血清生化参数、基因和蛋白表达。采用高效液相色谱法(HPLC)测定 FSE 中连翘苷 A 和连翘苷的含量。

结果

血清丙氨酸/天冬氨酸转氨酶(ALT/AST)活性和肝组织学评价结果均表明 FSE 对 CCl 诱导的肝损伤具有保护作用。进一步的,FSE 通过 Masson 三色和天狼猩红染色、肝羟脯氨酸含量以及血清透明质酸、层粘连蛋白、IV 型胶原和 III 型前胶原(PCIII)含量的结果,证实了其抗纤维化作用。FSE 还降低了 CCl 损伤小鼠肝脏中α-平滑肌肌动蛋白(α-SMA)的表达。此外,FSE 降低了 CCl 诱导的小鼠肝纤维化中纤维细胞特异性蛋白 1(FSP1)和波形蛋白的表达。

结论

FSE 通过抑制肝星状细胞(HSCs)的激活,减少肝细胞外基质(ECM)的分布,逆转上皮间质转化(EMT),减轻 CCl 诱导的小鼠肝纤维化。

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