实验动物科学 ›› 2019, Vol. 36 ›› Issue (05): 54-.

• 研究报告 • 上一篇    下一篇

小鼠慢性肝损伤周期性病变研究

  

  1. 首都医科大学实验动物部,北京 100069
  • 出版日期:2019-10-28 发布日期:2020-09-07

Study on Periodic Lesions in Mice with Chronic Liver Injury

  • Online:2019-10-28 Published:2020-09-07

摘要: 目的 研究四氯化碳(CCl4)诱导的小鼠慢性肝病模型肝损伤变化特征,并探讨其在医学研究中的应用。方法 正常BALB/c小鼠常规饲养1周后,腹腔注射0.5% CCl4溶液(10 μL/g,1次/3天,持续10周)。注射第2、4、6、8、10周后,取小鼠血清检测ALT、AST,同时取肝脏固定后进行HE、Masson染色,观察小鼠肝脏损伤变化。结果 CCl4溶液注射2周时,肝细胞损伤以变性为主,出现大量炎性细胞浸润和少量胶原蛋白沉积,ALT、AST轻度升高;4周时,肝细胞损伤以坏死为主(P<0.01),肝细胞数目(P<0.01)和炎性细胞浸润均减少(P<0.01),胶原蛋白沉积发展为条索状胶原纤维沉积,ALT、AST升高极显著(P<0.01);6周时,肝细胞坏死明显减少(P<0.01),肝细胞数目相对增多(P<0.01),炎性细胞浸润亦减少(P<0.01),胶原纤维沉积向胶原蛋白沉积转化(P<0.05),ALT、AST基本正常;8周时,肝细胞变性再次增多,伴随大量炎性细胞浸润(P<0.01),ALT、AST轻度升高;10周时,肝细胞损伤再次以坏死为主(P<0.01),肝细胞数目(P<0.01)及炎性细胞浸润减少(P<0.05),胶原蛋白沉积发展为条索状胶原纤维沉积,ALT、AST极显著升高(P<0.01)。结论 低剂量CCl4诱导小鼠慢性肝损伤存在明显、规律性肝损伤周期变化,在同一周期内,“损伤、坏死—再生、修复”顺序交替主导肝组织病理变化;针对不同的研究方向,应选取相应的“窗口期”进行肝脏损伤或修复的机制研究和药效评价。

关键词: 慢性肝损伤, BALB/c小鼠, 周期性病变

Abstract: Objective To observe changes in liver damage induced by carbon tetrachloride (CCl4)induced chronic liver disease in mice.Method One week after normal feeding in normal BALB/c mice,0.5% CCl4 solution (10 μL/g,one time every three days for 10 weeks,lasting 10 weeks)was intraperitoneally injected.After 2,4,6,8,and 10 weeks of injection,the serum ALT and AST were detected,HE and Masson staining after liver fixation,observation of liver structure,cell morphology and fibrosis degree in mice.Result When CCl4 solution was injected for 2 weeks,the liver cell damage was mainly denatured with a large number of inflammatory cells infiltration and a small amount of collagen deposition,and ALT and AST were slightly elevated;At 4 weeks,hepatocyte injury was mainly necrosis (P<0.01),and the number of hepatocytes (P<0.01)and inflammatory cell infiltration decreased (P<0.01).Collagen deposition developed into stripe collagen fiber deposition,and ALT and AST increased significantly(P<0.01);At 6 weeks,necrotic hepatocytes were significantly reduced (P<0.01),the number of hepatocytes increased (P<0.01),the infiltration of inflammatory cells was further reduced (P<0.01),collagen fiber deposition was transformed to collagen deposition (P<0.05),ALT and AST were basically normal(P<0.01));At 8 weeks,the degeneration of hepatocyte was increased again,with a large number of inflammatory cell infiltration (P<0.01),and a slight increase in ALT and AST;At 10 weeks,hepatocyte injury was mainly necrosis (P<0.01).The number of hepatocytes (P<0.01)and inflammatory cell infiltration decreased (P<0.05).Collagen deposition developed into stripe collagen fiber deposition,and ALT and AST increased significantly (P<0.01).Conclusion The chronic liver injury model of mice induced by 0.5%CCl4 solution has obvious and regular liver injury cycle changes,and the degeneration stage,necrotic stage and remission stage of hepatocyte appear in turn.

Key words: Chronic liver injury, BALB/c mice, periodic lesions