中国寄生虫学与寄生虫病杂志 ›› 2001, Vol. 19 ›› Issue (2): 4-79.

• 论著 • 上一篇    下一篇

日本血吸虫病兔肝纤维化胶原合成与降解转录水平的研究

陈峰,蔡卫民,陈智,刘荣华
  

  1. 浙江大学医学院附属第一医院传染病研究所!杭州310003
  • 收稿日期:1900-01-01 修回日期:1900-01-01 出版日期:2001-04-30 发布日期:2001-04-30

Studies on Synthesis and Degradation of Collagen at Transcription Level in Liver Fibrosis of Rabbits with Schistosomiasis japonica

CHEN Feng;CAI Wei-min;CHEN Zhi;LIU Rong-hua   

  1. Insitute of Infectious Diseases;First Affiliated Hospital of School of Medicine;Zhejiang University;Hangzhou 310003
  • Received:1900-01-01 Revised:1900-01-01 Online:2001-04-30 Published:2001-04-30

摘要:   目的 从转录水平研究日本血吸虫病兔肝纤维化形成过程中胶原的合成与降解。方法 以日本血吸虫尾蚴感染新西兰兔形成肝纤维化动物模型 ,分别于感染后第 4、6、8、10、12、16、2 0、2 4和 2 8周手术取肝脏组织 ,用RT PCR加dotblotting法检测肝组织Ⅰ型胶原、Ⅲ型胶原、Ⅳ型胶原以及降解胶原的基质金属蛋白酶MMP 1和MMP 9的mRNA水平 ,并进行肝组织病理学检测 ,观察虫卵肉芽肿大小和肝纤维化程度的变化。结果 在兔感染血吸虫初期 ,肝组织Ⅰ型胶原、Ⅲ型胶原、Ⅳ型胶原及MMP 1、MMP 9的mRNA水平均上升 ,在感染后第 10周达到峰值 ,Ⅰ型胶原、Ⅲ型胶原和Ⅳ型胶原mRNA水平分别是正常水平的 12 0、11 0和 6 6倍 ,MMP 1和MMP 9mRNA水平分别是正常水平的 10 0和 11 0倍 ,与虫卵肉芽肿反应变化一致。其后胶原和胶原酶mRNA均下降 ,至第 2 8周 ,Ⅰ型胶原、Ⅲ型胶原和Ⅳ型胶原mRNA水平降至正常水平的 2~ 3倍 (P <0 0 5 ) ,而MMP 1和MMP 9mRNA水平接近正常 (P >0 0 5 )。显示血吸虫感染初期胶原合成与降解处于平衡状态 ,而感染后期胶原的合成多于胶原的降解。结论 从转录水平证实血吸虫病兔肝脏肉芽肿反应胶原合成大于降解 ,从而导致肝纤维化形成

关键词: 日本血吸虫病, 肝纤维化, 胶原酶, mRNA, RT-PCR

Abstract:  Objective To study the synthesis and degradation of collagen at the transcription level during liver fibrosis in rabbits with schistosomiasis japonica. Methods New Zealand rabbits infected with Schistosoma japonicum cercariae were served as animal models of liver fibrosis. The liver specimens were collected through operations at 4, 6, 8, 10, 12, 16, 20, 24 and 28 weeks after infection. TypeⅠcollagen, type Ⅲ collagen, type Ⅳ collagen, MMP-1 and MMP-9 mRNA levels of liver tissue were detected by RT-PCR plus dot blotting, and the size of egg granulomas and the degree of liver fibrosis were measured by histopathological examinations. Results TypeⅠcollagen, type Ⅲ collagen, type Ⅳ collagen, MMP-1 and MMP-9 mRNA levels increased simultaneously in the early stage after the infection, mostly reaching their peaks at 10 weeks after infection. Compared with normal controls, type Ⅰ collagen, type Ⅲ collagen, type Ⅳ collagen, MMP-1 and MMP-9 mRNA levels increased by 12.0 , 11.0 , 6.6 , 10.0 and 11.0-fold, respectively, coinciding with the changes of egg granulomas. Thereafter, both collagen and collagenase mRNA levels decreased. TypesⅠ, Ⅲ and Ⅳ collagen mRNA levels declined to 2-fold to 3-fold compared with normal controls ( P <0.05), while MMP-1 and MMP-9 mRNA levels declined to normal level ( P >0.05) at 28 weeks. This study showed that the synthesis and degradation of collagen remained dynamic balance in the early stage of schistosomiasis, while in the later stage the metabolism of collagen synthesis was higher than that of collagen degradation. Conclusion It was confirmed at the transcription level that when the metabolism of collagen synthesis was higher than that of collagen degradation in rabbits with schistosomiasis japonica, liver fibrosis might be produced.

Key words: schistosomiasis japonica, liver fibrosis, collagenase, mRNA, RT-PCR