Chen Feng, Cai Weimin, Chen Zhi, Chen Xiangming, Liu Ronghua
Institute of Infectious Diseases, 1st Affiliated Hospital of Zhejiang University, School of Medicine Hangzhou 310003, China.
Chin Med J (Engl). 2002 Nov;115(11):1637-40.
To study the role of the synthesis and degradation of collagen at the transcription level during liver fibrogenesis due to schistosomiasis japonica in rabbits.
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.
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.
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.
研究日本血吸虫病致兔肝纤维化过程中转录水平上胶原蛋白合成与降解的作用。
用日本血吸虫尾蚴感染新西兰兔作为肝纤维化动物模型。在感染后4、6、8、10、12、16、20、24和28周通过手术采集肝脏标本。采用逆转录聚合酶链反应+斑点杂交法检测肝组织中Ⅰ型胶原、Ⅲ型胶原、Ⅳ型胶原、基质金属蛋白酶-1（MMP-1）和基质金属蛋白酶-9（MMP-9）的mRNA水平。通过组织病理学检查测量虫卵肉芽肿大小和肝纤维化程度。
感染后早期，Ⅰ型胶原、Ⅲ型胶原、Ⅳ型胶原、MMP-1和MMP-9的mRNA水平同时升高。大多数在10周时达到峰值，与正常对照组相比，Ⅰ型胶原、Ⅲ型胶原、Ⅳ型胶原、MMP-1和MMP-9的mRNA水平分别升高了12.0倍、11.0倍、6.6倍、10.0倍和11.0倍，与虫卵肉芽肿的变化即炎症过程的变化一致。然后胶原蛋白和胶原酶的mRNA水平均下降。在28周时，Ⅰ型、Ⅲ型和Ⅳ型胶原的mRNA水平降至比正常对照组高2至3倍（P<0.05），而MMP-1和MMP-9的mRNA水平降至接近正常水平（P>0.05）。本研究表明，日本血吸虫感染早期胶原蛋白的合成与降解保持动态平衡，而后期胶原蛋白合成量高于降解量。
在转录水平证实，当胶原蛋白合成量高于降解量时可能导致肝纤维化。
