Gui Shuang-Ying, Wei Wei, Wang Hua, Wu Li, Sun Wu-Yi, Chen Wen-Bi, Wu Cheng-Yi
Institute of Clinical Pharmacology, Anhui Medical University, Anhui Province, Hefei 230032, PR China.
J Ethnopharmacol. 2006 Jan 16;103(2):154-9. doi: 10.1016/j.jep.2005.07.025. Epub 2005 Sep 29.
Astragalosides is the major active constituent of Radix Astragali. The present study was carried out to investigate the effect of crude astragalosides fraction (CAF) on rats liver fibrosis and its possible mechanisms. Hepatic fibrosis was induced by subcutaneous injection with 50% CCl(4) in Sprague-Dawley rats. The amount of CCl(4) administered was 1 mg kg(-1). The alanine aminotransferase (ALT), aspartate aminotransferase (AST) levels in plasma and hydroxyproline (Hyp), malondialdehyde (MDA), superoxide dismutase (SOD) and glutathione peroxidase (GSH-px) contents in liver tissue were assayed by spectrophotometry. The hyaluronic acid (HA) and procollagen III (PC III) were assessed by radioimmunoassay. Tumor necrosis factor-alpha (TNF-alpha) and transforming growth factor-beta1 (TGF-beta1) levels in culture supernatants of Kupffer cells (KCs) were determined with ELISA. Liver samples collected after 8 weeks of CCl(4) treatment were stained with hematoxylin-eosin (HE) and massion, and scored. Intragastric administration of CAF (10, 20 and 40 mg kg(-1)) significantly decreased indices of liver and spleen, the serum transaminase activities, HA and PC III levels, and Hyp and MDA contents in liver tissue in rats of hepatic fibrosis. Decreased SOD and GSH-px levels were reversed after administration of CAF. Histopathological scores showed CAF had inhibitory effect on the progression of hepatic fibrosis. In the in vitro experiments, CAF significantly reduced TNF-alpha and TGF-beta1 levels in culture supernatants of KCs. The results showed CAF significantly inhibited the progression of hepatic fibrosis induced by CCl(4), and the inhibitory effect of CAF on hepatic fibrosis might be associated with its ability to scavenge free radical and inhibit the production of TNF-alpha and TGF-beta1 from activated KCs.
黄芪皂苷是黄芪的主要活性成分。本研究旨在探讨黄芪皂苷粗提物（CAF）对大鼠肝纤维化的影响及其可能机制。采用皮下注射50%四氯化碳（CCl₄）诱导Sprague-Dawley大鼠肝纤维化，CCl₄给药量为1 mg·kg⁻¹。采用分光光度法检测血浆中丙氨酸氨基转移酶（ALT）、天冬氨酸氨基转移酶（AST）水平以及肝组织中羟脯氨酸（Hyp）、丙二醛（MDA）、超氧化物歧化酶（SOD）和谷胱甘肽过氧化物酶（GSH-px）含量。采用放射免疫法检测透明质酸（HA）和Ⅲ型前胶原（PCⅢ）。采用酶联免疫吸附测定法（ELISA）检测库普弗细胞（KCs）培养上清液中肿瘤坏死因子-α（TNF-α）和转化生长因子-β1（TGF-β1）水平。CCl₄处理8周后采集肝脏样本，进行苏木精-伊红（HE）染色和Masson染色并评分。胃内给予CAF（10、20和40 mg·kg⁻¹）可显著降低肝纤维化大鼠的肝脾指数、血清转氨酶活性、HA和PCⅢ水平以及肝组织中Hyp和MDA含量。给予CAF后，降低的SOD和GSH-px水平得到逆转。组织病理学评分显示CAF对肝纤维化进展具有抑制作用。在体外实验中，CAF显著降低KCs培养上清液中TNF-α和TGF-β1水平。结果表明，CAF显著抑制CCl₄诱导的肝纤维化进展，其对肝纤维化的抑制作用可能与其清除自由基以及抑制活化KCs产生TNF-α和TGF-β1的能力有关。
