Anhui Medical University, China.
J Pharm Pharmacol. 2010 Jul;62(7):935-42. doi: 10.1211/jpp.62.07.0016.
The study was to investigate the prevention effects and possible mechanism of Yu Ping Feng San fractioned polysaccharide (YPF-P) on CCl(4)-induced liver fibrosis in rats.
YPF-P was prepared from root of Astragalus membranaceus, rhizome of Atractylodes macrocephaia and root of Raidix saposhnikoviae, and compared with polysaccharide from root of Astragalus membranaceus (AP). Hepatic fibrosis was induced by subcutaneous injection with carbon tetrachloride twice weekly for 12 weeks in Sprague-Dawley rats. YPF-P, AP and colchicine were administered intragastrically daily to carbon tetrachloride-treated rats. Histopathological changes of the liver and hepatic stellate cells were evaluated by Masson staining and transmission electron microscopy, respectively. Markers of fibrosis were determined by radioimmunoassay, biochemistry assay and ELISA. The mRNA expressions of tissue inhibitor of metalloproteinase-1 (TIMP-1), matrix metalloproteinase-13 (MMP-13), procollagen I and collagen III were detected by RT-PCR.
YPF-P dose-dependently alleviated the degree of liver fibrosis and inhibited hepatic stellate cell transformation into myofibroblast-like cells, markedly reduced the elevated levels of hyaluronic acid, laminin, type IV collagen, type III procollagen, hydroxyproline and transforming growth factor beta-1, suppressed procollagen I, collagen III and TIMP-1 expression, and improved the TIMP-1/MMP-13 ratio. MMP-13 expression was only promoted moderately by YPF-P. Compared with AP, YPF-P showed more potency on most markers except laminin, type IV collagen and MMP-13 mRNA.
YPF-P prevented the progress of rat liver fibrosis induced by carbon tetrachloride and had a more potent preventative effect. The preventative effect may be associated with the ability of YPF-P to inhibit the synthesis of matrix collagen and balance the TIMP/MMP system.
研究玉屏风散分部位多糖（YPF-P）对四氯化碳诱导的大鼠肝纤维化的预防作用及其可能的机制。
采用玉屏风散（黄芪、白术、防风）的根部分离多糖，并与黄芪多糖（AP）进行比较。每周两次皮下注射四氯化碳，共 12 周，诱导 Sprague-Dawley 大鼠肝纤维化。将 YPF-P、AP 和秋水仙碱灌胃给予四氯化碳处理的大鼠。通过 Masson 染色和透射电镜分别评估肝组织和肝星状细胞的组织学变化。用放射免疫法、生化测定和 ELISA 测定纤维化标志物。用 RT-PCR 检测组织金属蛋白酶抑制剂-1（TIMP-1）、基质金属蛋白酶-13（MMP-13）、前胶原 I 和胶原 III 的 mRNA 表达。
YPF-P 呈剂量依赖性减轻肝纤维化程度，抑制肝星状细胞向肌成纤维细胞样细胞转化，显著降低透明质酸、层粘连蛋白、IV 型胶原、III 型前胶原、羟脯氨酸和转化生长因子-β1 的升高水平，抑制前胶原 I、胶原 III 和 TIMP-1 的表达，并改善 TIMP-1/MMP-13 比值。YPF-P 仅适度促进 MMP-13 的表达。与 AP 相比，YPF-P 在大多数标志物上表现出更强的作用，除了层粘连蛋白、IV 型胶原和 MMP-13mRNA。
YPF-P 可预防四氯化碳诱导的大鼠肝纤维化进展，具有更强的预防作用。预防作用可能与 YPF-P 抑制基质胶原合成和平衡 TIMP/MMP 系统的能力有关。
