Sun Wuyi, Gui Shuangying, Wu Li, Wang Hua, Wei Wei
Institute of Clinical Pharmacology, Anhui Medical University, Key Laboratory of Anti-inflammatory and Immunopharmacology of Education Ministry, Anhui Engineering Technology Research Center of Anti-inflammatory and Immunodrugs, Hefei 230032, China.
Zhongguo Zhong Yao Za Zhi. 2010 Jun;35(11):1447-51.
To investigate the effects of Shaoqiduogan (SQDG) on the expression of matrix metalloproteinase 13 (MMP-13) and tissue inhibitor of metalloproteinase 1 (TIMP-1) in carbon tetrachloride (CCl4) induced hepatic fibrosis rats and transforming growth factor beta1 (TGF-beta1) irritated hepatic stellate cells (HSC), and to explore its possible mechanisms.
The model of chemical hepatic fibrosis induced by CCl4 was prepared. The rats were randomly divided into 5 groups, including normal control group, liver fibrosis model group and SQDG (42. 5, 85, 170 mg x kg(-1)) treated groups. The level of collagen type 1 (C-1) in serum was determined by radioimmunoassay. Masson stain was used to examine the histopathological change. MMP-13 and TIMP-1 ex-pression in liver tissues were assayed by immunohistochemistry. In vitro, effects of SQDG on the expression of MMP-13, TIMP-1 and C-1 in HSC-T6 stimulated by TGF-beta were measured by Western-blot.
The results showed that SQDG significantly decreased the elevated level of C-1 in serum of hepatic fibrosis rats induced by CCl4. Pathological examination showed that SQDG could remarkably alleviate the degree of liver fibrogenesis and formation of pseudolobulus. The results of immunohistochemistry demonstrated that SQDG significantly increased MMP-13 expression and decreased TIMP-1 expression in liver tissues. Furthermore, SQDG (20-160 mg x L(-1)) could facilitate MMP-13 expression, inhibit TIMP-1 expression and significantly inhibit the C-I production of HSC stimulated with TGF-beta1 in vitro.
The anti-fibrotic effects of SQDG may be associated with its action of promoting collagen degradation via controlling the levels of MMP-13 and TIMP-1 in liver.
探讨少芪多苷（SQDG）对四氯化碳（CCl4）诱导的肝纤维化大鼠基质金属蛋白酶13（MMP - 13）和金属蛋白酶组织抑制剂1（TIMP - 1）表达的影响，以及对转化生长因子β1（TGF - β1）刺激的肝星状细胞（HSC）的影响，并探讨其可能机制。
制备CCl4诱导的化学性肝纤维化模型。将大鼠随机分为5组，包括正常对照组、肝纤维化模型组和SQDG（42.5、85、170mg·kg⁻¹）治疗组。采用放射免疫法测定血清Ⅰ型胶原（C - 1）水平。用Masson染色法检查组织病理学变化。采用免疫组织化学法检测肝组织中MMP - 13和TIMP - 1的表达。体外实验中，用蛋白质免疫印迹法检测SQDG对TGF - β刺激的HSC - T6中MMP - 13、TIMP - 1和C - 1表达的影响。
结果显示，SQDG显著降低了CCl4诱导的肝纤维化大鼠血清中升高的C - 1水平。病理检查表明，SQDG可显著减轻肝纤维化程度和假小叶形成。免疫组织化学结果显示，SQDG显著增加肝组织中MMP - 13的表达，降低TIMP - 1的表达。此外，SQDG（20 - 160mg·L⁻¹）可促进体外TGF - β1刺激的HSC中MMP - 13的表达，抑制TIMP - 1的表达，并显著抑制C - Ⅰ的产生。
SQDG的抗纤维化作用可能与其通过控制肝脏中MMP - 13和TIMP - 1水平促进胶原降解的作用有关。
