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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、2 0、2 4和 2 8周手术取肝脏组织 ,用RT PCR加Dotblot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 - 9mRNA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 9mRNA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 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 )。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。
Objective To study the synthesis and degradation of collagen during the formation of liver fibrosis in Schistosoma japonicum from the transcriptional level. Methods New Zealand rabbits were infected with Schistosoma japonicum to form hepatic fibrosis animal models. Liver tissues were harvested at 4, 6, 8, 10, 12, 16, 20, 24 and 28 weeks after infection. The mRNA levels of MMP-1 and MMP-9 in type Ⅰ, type Ⅲ, type Ⅳ collagen and collagen degradation in liver tissue were detected. The pathological changes of hepatic fibrosis and egg granuloma were observed. Results The levels of collagen type Ⅰ, type Ⅲ collagen, type Ⅳ collagen, MMP - 1 and MMP - 9 mRNA in liver tissue of rabbits infected with Schistosoma japonicum increased at the initial stage, and most of them reached the peak at the 10th week after infection, and the mRNA level of type Ⅰ collagen was normal , 120 times for type Ⅲ collagen and 66% for type Ⅳ collagen respectively. The mRNA levels of MMP-1 and MMP-9 were 10 0 times and 10 0 times that of normal, respectively, which were roughly the same as that of granuloma of ovum Change consistent. Collagen and collagenase mRNA levels decreased afterwards. By 28 weeks, mRNA levels of type I collagen, type III collagen and type IV collagen were reduced to 2 to 3 folds of normal (P <0 05), while MMP 1 and MMP 9 mRNA level close to normal (P> 0 05). This study shows that the initial synthesis and degradation of collagen in the initial stage of schistosome infection in equilibrium, and collagen synthesis in post-infection more than collagen degradation. Conclusions Transcript levels confirm that collagen synthesis is greater than degradation and lead to hepatic fibrosis.