Abdelrahman Shaimaa A, Abdelfatah Mohammed M, Keshta Akaber T
Medical Histology and Cell Biology Department, Faculty of Medicine, Zagazig University, Zagazig, Egypt.
Biochemistry Division, Chemistry Department, Faculty of Science, Zagazig University, Zagazig, Egypt.
Iran J Basic Med Sci. 2022 Jun;25(6):732-744. doi: 10.22038/IJBMS.2022.64034.14101.
Thioacetamide (TAA) was administered to induce an animal model of liver disease with secondary splenomegaly to assess the mechanisms underlying the effects of rapamycin and filgrastim when taken separately or in combination on the biochemical and histopathological aspects of the liver and spleen.
Thirty adult male albino rats were divided into five groups (control, TAA-treated group, TAA+rapamycin, TAA+filgrastim, and TAA+rapamycin+filgrastim group). We measured relative liver and spleen weights, serum levels of alanine transaminase (ALT), aspartate transaminase (AST), and albumin. Molecular docking modeling and histopathological examination of liver and spleen sections with hematoxylin and eosin and Masson trichrome staining with immunohistochemical detection of splenic CD3 and CD20 lymphocytes, S100A9 and β actin antibodies were detected. Morphometric and statistical analyses of the results were performed.
TAA administration altered the histological structure of the liver and spleen and impaired liver function. It increased the expression of splenic CD3, CD20 lymphocytes, and S100A9 while diminishing the expression of β actin. Each of rapamycin and filgrastim, when administered separately, improved liver and spleen indices and liver function, but rapamycin did not affect the albumin level. They lowered splenic B and T lymphocyte levels. Expression levels of S100A9 showed down-regulation while β actin levels were up-regulated when compared with TAA. Combination therapy improved liver and spleen tissue pathology and significantly ameliorated the expression of splenic lymphocytes through regulation of S100A9 and β actin expression.
The synergistic effect of combination therapy was dependent on the regulation of splenic S100A9 and β actin levels.
给予硫代乙酰胺（TAA）以诱导继发性脾肿大的肝病动物模型，以评估雷帕霉素和非格司亭单独或联合使用时对肝脏和脾脏的生化及组织病理学方面影响的潜在机制。
将30只成年雄性白化病大鼠分为五组（对照组、TAA治疗组、TAA+雷帕霉素组、TAA+非格司亭组和TAA+雷帕霉素+非格司亭组）。我们测量了肝脏和脾脏的相对重量、血清丙氨酸转氨酶（ALT）、天冬氨酸转氨酶（AST）和白蛋白水平。对肝脏和脾脏切片进行苏木精-伊红染色及Masson三色染色的分子对接建模和组织病理学检查，并用免疫组织化学法检测脾脏CD3和CD20淋巴细胞、S100A9和β肌动蛋白抗体。对结果进行形态计量学和统计学分析。
给予TAA改变了肝脏和脾脏的组织结构并损害了肝功能。它增加了脾脏CD3、CD20淋巴细胞和S100A9的表达，同时降低了β肌动蛋白的表达。雷帕霉素和非格司亭单独使用时，均改善了肝脏和脾脏指标及肝功能，但雷帕霉素不影响白蛋白水平。它们降低了脾脏B和T淋巴细胞水平。与TAA相比，S100A9的表达水平下调，而β肌动蛋白水平上调。联合治疗改善了肝脏和脾脏组织病理学，并通过调节S100A9和β肌动蛋白的表达显著改善了脾脏淋巴细胞的表达。
联合治疗的协同作用取决于脾脏S100A9和β肌动蛋白水平的调节。
