兔日本血吸虫病肝纤维化胶原代谢的转录水平动态变化
Dynamic changes in the collagen metabolism of liver fibrosis at the transcription level in rabbits with Schistosomiasis japonica
目的从转录水平研究兔日本血吸虫病肝纤维化形成过程中胶原的合成与降解的规律.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,于感染后4、6、8、10、12、16、20、24和28周手术取肝脏组织,用RT-PCR加Dot blot法检测肝组织Ⅰ型、Ⅲ型、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、MMP-1和MMP-9 mRNA水平均上升,且大多在感染后第10周达到峰值,Ⅰ型胶原mRNA水平是正常的12.0倍,Ⅲ型胶原为11.0倍,Ⅳ型胶原为6.6倍,MMP-1和MMP-9 mRNA水平分别是正常水平的10.0倍和11.0倍,大致与虫卵肉芽肿,即炎症反应变化一致.其后胶原和胶原酶mRNA均下降,至28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<0.05),而MMP-1和MMP-9 mRNA水平接近正常(P>0.05).本研究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胶原合成大于降解时可导致肝纤维化形成.
更多Objective To study the role of the synthesis and degradation of collagen at the transcription level during liver fibrogenesis due to schistosomiasis japonica in rabbits. Methods New Zealand rabbits challenged by cercariae of Schistosoma japonicum (S. japonicum) were served as animal models for liver fibrosis. Liver specimens were collected through operations at 4, 6, 8, 10, 12, 16, 20, 24 and 28 wks after challenge. Type Ⅰ collagen, type Ⅲ collagen, type Ⅳ collagen, MMP-1 and MMP-9 mRNA levels of liver tissue were detected by RT-PCR+Dot blot. The size of egg granulomas and the degree of liver fibrosis were measured by histopathological examinations. Results Type Ⅰ collagen, type Ⅲ collagen, type Ⅳ collagen, MMP-1 and MMP-9 mRNA levels increased simultaneously in the early stage after challenge. Most of them reached their peak at 10 weeks, and 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 change of egg granulomas, i.e., the change in the inflammatory process. Then both collagen and collagenase mRNA levels decreased. Type Ⅰ, Ⅲ and Ⅳ collagen mRNA levels declined to 2-fold to 3-fold as compared with normal controls (P<0.05), while MMP-1 and MMP-9 mRNA levels declined close to normal levels (P>0.05) at 28 wks. This study shows that the synthesis and degradation of collagen keep a dynamic balance at the early stage of schistosomiasis japonica challenge, while at the later stages the quantity of collagen synthesis was higher than that of collagen degradation. Conclusions It was confirmed at transcription level that when the quantity of collagen synthesis was higher than that of collagen degradation liver fibrogenesis may be resulted in.
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