Biology Department, Faculty of Science, UAE University, Al-Ain, United Arab Emirates.
Acta Biochim Biophys Sin (Shanghai). 2011 Mar;43(3):193-203. doi: 10.1093/abbs/gmq129. Epub 2011 Jan 21.
Chronic hepatic injury results in liver fibrosis with eventual progression to irreversible cirrhosis. Liver fibrogenesis involves the activation of the quiescent hepatic stellate cell into an activated myofibroblast that is characterized by α-smooth muscle actin (α-SMA) expression and the production of collagens (types I and III). In the present study, rats were randomly divided into three groups: (i) control group, where rats were only treated with a vehicle; (ii) fibrosis group, where rats were treated with carbon tetrachloride (CCl(4)) to induce liver fibrosis; and (iii) silymarin group, where rats were protected with silymarin during CCl(4) treatment. Rats were sacrificed and sections of liver tissue were counterstained with hematoxylin and eosin and Masson's trichrome. Other sections were immunostained using collagens and α-SMA primary antibodies. Fibrosis was confirmed using serum marker measurements. Microscopic images of the stained sections were acquired and digitized. The Biomarker Index of Fibrosis (BIF) was calculated from the images by quantifying the percentage of stained fibers. Statistical methods of texture analysis (TA), namely co-occurrence and run-length matrices, were applied on the digital images followed by classification using agglomerative hierarchical clustering and linear discriminant analysis with cross validation. TA applied on different biomarkers was successful in discriminating between the groups, showing 100% sensitivity and specificity for classification between the control and fibrosis groups using any biomarker. Some classification attempts showed dependence on the biomarker used, especially for classification between the silymarin and fibrosis groups, which showed optimal results using Masson's trichrome. TA results were consistent with both BIF and serum marker measurements.
慢性肝损伤导致肝纤维化，最终发展为不可逆转的肝硬化。肝纤维化的发生涉及到静止的肝星状细胞被激活为肌成纤维细胞，其特征是α-平滑肌肌动蛋白（α-SMA）的表达和胶原（I 型和 III 型）的产生。在本研究中，大鼠被随机分为三组：（i）对照组，大鼠仅用载体处理；（ii）纤维化组，大鼠用四氯化碳（CCl(4)）处理诱导肝纤维化；（iii）水飞蓟素组，大鼠在 CCl(4)处理期间用水飞蓟素保护。处死大鼠，用苏木精和伊红以及 Masson 三色染色对肝组织切片进行复染。用胶原和 α-SMA 一抗对其他切片进行免疫染色。通过血清标志物测量确认纤维化。获取和数字化染色切片的显微图像。通过量化染色纤维的百分比，从图像计算出纤维化生物标志物指数（BIF）。对数字图像应用纹理分析（TA）的统计方法，即共生和行程长度矩阵，然后使用凝聚层次聚类和带有交叉验证的线性判别分析进行分类。TA 应用于不同的生物标志物可成功区分各组，使用任何生物标志物对控制组和纤维化组进行分类的敏感性和特异性均为 100%。一些分类尝试显示出对所使用的生物标志物的依赖性，尤其是对水飞蓟素和纤维化组之间的分类，使用 Masson 三色显示出最佳结果。TA 结果与 BIF 和血清标志物测量一致。
