Department of Hepatobiliary and Pancreatic Surgery, the Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou 310009, China.
J Zhejiang Univ Sci B. 2013 Jan;14(1):68-75. doi: 10.1631/jzus.B1200112.
Hepatic sinusoidal obstruction syndrome (HSOS) is characterized by painful hepatomegaly, ascites, increased body weight, and jaundice. Gynura segetum (Compositae), a plant widely used in Chinese traditional medicine, often leads to the development of HSOS. However, the mechanism is unclear. The aim was to study the role of matrix metalloproteinase-9 (MMP-9) in the onset of HSOS induced by Gynura segetum.
Twenty-five male Sprague-Dawley rats were randomly divided into two groups. Twenty were exposed to 600 mg/kg daily Gynura segetum extract solution for three weeks; five control rats were exposed to tap water alone. Liver sections were evaluated by light microscopy with a modified scoring system. Routine transmission electron microscopy (TEM) methods were used to evaluate the ultrastructual features of fixed liver tissue, and blood samples were collected to determine liver enzyme concentrations. MMP-9 expression was assessed by both immunohistochemical staining and enzyme-linked immunosorbent assay (ELISA) methods.
A stable and reproducible rat model of HSOS was achieved by long-term exposure to Gynura segetum extract. The treated rats presented clinical symptoms and the histopathological manifestation of HSOS, including abnormal liver enzyme concentrations (alanine aminotransferase (ALT): (84.8±13.62) vs. (167.0±72.63) U/L, P<0.05; aspartate aminotransferase (AST): (27.6±6.31) vs. (232.8±108.58) U/L, P<0.05). Hematoxylin and eosin (H&E) staining and TEM together revealed deposition of red blood cells, the damage and destruction of hepatic sinusoidal endothelial cells, collapse of hepatic sinusoids, hemorrhage of subendothelial cells, atrophy and destruction of hepatocytes, etc. Compared with controls, the expression of MMP-9 in the blood sample, the lung and liver tissues of HSOS rats was increased.
MMP-9 may have an important role in early pathological changes of HSOS, and thus the onset of the disease.
肝窦阻塞综合征（HSOS）的特征为肝肿大、腹痛、体重增加和黄疸。三叶鬼针草（菊科）是一种广泛应用于中药的植物，常导致 HSOS 的发生。然而，其机制尚不清楚。本研究旨在探讨基质金属蛋白酶-9（MMP-9）在三叶鬼针草诱导的 HSOS 发病中的作用。
25 只雄性 Sprague-Dawley 大鼠随机分为两组，20 只给予 600mg/kg/天三叶鬼针草提取物溶液，连续 3 周；5 只对照组大鼠给予自来水。采用改良评分系统对肝组织进行光镜评估，常规透射电镜（TEM）方法观察固定肝组织的超微结构特征，采集血样测定肝酶浓度。采用免疫组化染色和酶联免疫吸附试验（ELISA）方法评估 MMP-9 的表达。
通过长期暴露于三叶鬼针草提取物，成功建立了稳定且可重现的 HSOS 大鼠模型。治疗组大鼠出现临床症状和 HSOS 的组织病理学表现，包括异常的肝酶浓度（丙氨酸氨基转移酶（ALT）：（84.8±13.62）vs.（167.0±72.63）U/L，P<0.05；天冬氨酸氨基转移酶（AST）：（27.6±6.31）vs.（232.8±108.58）U/L，P<0.05）。苏木精-伊红（H&E）染色和 TEM 共同显示红细胞沉积、肝窦内皮细胞损伤和破坏、肝窦塌陷、内皮下细胞出血、肝细胞萎缩和破坏等。与对照组相比，HSOS 大鼠血液样本、肺组织和肝组织中 MMP-9 的表达增加。
MMP-9 可能在 HSOS 的早期病理变化中发挥重要作用，从而导致疾病的发生。
