Hayasaka A, Koch J, Schuppan D, Maddrey W C, Hahn E G
Department of Medicine, Jefferson Medical College, Philadelphia, PA.
J Hepatol. 1991 Nov;13(3):328-38. doi: 10.1016/0168-8278(91)90077-o.
Serum concentrations of the aminoterminal propeptide of procollagen type III (PIIIP) are elevated in fibrogenic diseases of the liver, but the mechanism of elevation is not fully understood. To investigate the mechanism, we compared serum concentrations of PIIIP with total liver content of mRNA for the pro alpha 1 (III) chain, in rats with carbon tetrachloride (CCl4)-induced liver fibrosis. Adult male rats received CCl4 in mineral oil twice weekly for 8 weeks and were compared with age-matched controls. Serum concentrations of PIIIP were measured by a specific radioimmunoassay; molecular sizes of PIIIP in serum were also determined. Pro alpha 1 (III) mRNA content in the liver was quantitated by RNA slot-blot hybridization and chemical measurement of total hepatic RNA content. Total collagen content of the liver was estimated by hydroxyproline measurement. All CCl4-treated animals had septal fibrosis after 4 weeks, and evidence of cirrhosis (regenerative nodules, ascites) was seen after 7 weeks of treatment. Serum concentrations of PIIIP and pro alpha 1 (III) mRNA content in the liver were correlated well until cirrhosis has established. They increased simultaneously after 3 weeks of treatment, 1 week before any elevation of hepatic hydroxyproline could be detected. After cirrhosis has established, pro alpha 1 (III) mRNA content in the liver decreased markedly, but serum PIIIP levels continued to be elevated. Hepatic hydroxyproline plateaued after 5 weeks. The molecular sizes of serum PIIIP indicate the release of intact native procollagen peptide during the development of cirrhosis. In conclusion, at least in CCl4-induced liver fibrosis in the rats, serum PIIIP levels can be used as a fibrogenic marker for the period progressing to cirrhosis. But the use of the serum PIIIP levels in cirrhosis seems to be limited by factors other than liver fibrogenesis.
在肝脏纤维化疾病中，血清III型前胶原氨基端前肽（PIIIP）浓度会升高，但其升高机制尚未完全明确。为研究该机制，我们比较了四氯化碳（CCl4）诱导的肝纤维化大鼠血清PIIIP浓度与肝脏中前α1（III）链mRNA的总量。成年雄性大鼠每周两次接受溶于矿物油的CCl4，持续8周，并与年龄匹配的对照组进行比较。通过特异性放射免疫测定法测量血清PIIIP浓度；同时还测定了血清中PIIIP的分子大小。通过RNA斑点杂交和化学方法测量肝脏总RNA含量，对肝脏中前α1（III）mRNA含量进行定量。通过羟脯氨酸测量估算肝脏总胶原蛋白含量。所有接受CCl4处理的动物在4周后出现间隔纤维化，治疗7周后出现肝硬化（再生结节、腹水）迹象。在肝硬化形成之前，血清PIIIP浓度与肝脏中前α1（III）mRNA含量密切相关。治疗3周后它们同时升高，此时在检测到肝脏羟脯氨酸升高之前1周。肝硬化形成后，肝脏中前α1（III）mRNA含量明显下降，但血清PIIIP水平持续升高。肝脏羟脯氨酸在5周后达到稳定水平。血清PIIIP的分子大小表明在肝硬化发展过程中完整的天然前胶原肽被释放。总之，至少在大鼠CCl4诱导的肝纤维化中，血清PIIIP水平可作为进展至肝硬化阶段的纤维化标志物。但在肝硬化中使用血清PIIIP水平似乎受到肝脏纤维化以外因素的限制。
