摘要
目的:观察胆汁淤积性大鼠肝硬化形成过程中模型动态变化特点。方法:结扎大鼠胆总管制备大鼠胆汁淤积性肝硬化模型;结扎后3天、1周、2周、3周、4周、5周后杀鼠取材,观测大鼠一般状况,肝功能、肝组织羟脯氨酸(Hyp)含量测定,肝组织病理学及CK-19免疫组织化学观察。结果:与假手术组大鼠比较,模型组大鼠肝重、脾重、肝/体比、脾/体比均呈先增加后降低的动态变化;血清Alb含量持续下降,而TP含量呈先高后低的变化;血清ALT活性在结扎3天后最高,2周时最低;GGT活性及TBil含量自造模后呈持续增高;而ALP活性在2周时最高;肝组织Hyp含量从结扎后呈持续增加;结扎3天后汇管区已见胆管增生,至3周时增生逐渐加重。CK-19免疫组织化学染色观察,胆管上皮细胞第3天起开始增生,1周、2周时增生明显,3周后增生渐减。4周、5周时肝组织呈花环样改变,肝实质细胞显著减少。可见肝细胞去分化现象。结论:①胆汁淤积性大鼠肝硬化模型主要病理改变有胆汁淤积、胆管上皮细胞增生、肝细胞减少、胶原增生和沉积与新生的胆管上皮细胞关系密切。②血清ALT水平由高到低,5周末仅比假手术组稍高。AST活性一直维持在较高水平。③肝细胞的减少方式除了凋亡、坏死外,可见去分化现象。
Objective： To study dynamic pathology changes of cholestatic cirrhosis in rats. Methods： Cholestatic cirrhosis in rats was duplicated by ligation of bile duct, rats were sacrificed after 3d, 1W, 2W, 3W, 4W and 5W of ligation for dynamic study histological changes, liver function, Hyp content in liver tissue and CK-19 expression in proliferated bile duct were determined with lie staining, biochemisty and immunohistochemistry. Results： Compared with sham operation group, increase in body weight in model group was obviously lowered; liver weight, spleen weight, liver/body ratio and spleen/body ratio increased at first stage, then decreased at late stage; serum Alb content decreased continuously, while TP increased first and then decreased later; serum ALT and AST activity peaked after 3d of ligation, then valleyed at 2W of ligation and maintain a low level from 3W of ligation, but still being higher than that in sham operation group; serum GGT activity and TBil content increased continuously, while ALP activity peaked at 2W of modeling, then decreased and maimained at a low level; Hyp content in liver tissue increased continuously; bile duct proliferation in periportal area was seen from 3d of ligatlon, this proliferation continued from lW to 3W of modeling, and proliferated cholanglocytes formed srnall bile duct, and at the same time, differentiation was seen in hepatocytes. Proliferated small bile duct, fibroblast and collagen formed septa reconstructed lobule to form pseusolobule. Normal hepatocytes were rarely seen in rats liver tissue at 4W and 5W of modeling. CK-19 expression showed that cholangiocytes proliferated from 3d of modeling and continuously increased with 2W, while this proliferation decreased from 3W of modeling. Conclusion： The main pathological changes in rat cholestatic cirrhosis are cholestasis, cholangiocytes proliferation, decrease in hepatocytes number, new proliferated cholangiocytes related deposition of collagen; serum ALT and AST activity increases first and then decreases later, No definite correlation is seen between spleen weight and cirrhosis; decreases in hepatocytes number is not only attributed to apoptosis and necrosis, but also to differentiation like changes.
出处
《中西医结合肝病杂志》
CAS
2006年第2期87-89,共3页
Chinese Journal of Integrated Traditional and Western Medicine on Liver Diseases
基金
上海市自然科学基金重点项目资金资助(No.04DZ19845)
