Koda M, Murawaki Y, Hirayama C
Second Department of Internal Medicine, Tottori University School of Medicine, Yonago, Japan.
Biochem Biophys Res Commun. 1988 Mar 30;151(3):1128-35. doi: 10.1016/s0006-291x(88)80483-2.
To clarify the process of free and small peptide-bound hydroxyproline synthesis in hepatic fibrogenesis, we measured the in vitro synthesis of [14C]hydroxyproline in the 67% ethanol soluble fraction in rat liver slices, together with hepatic protein-bound [14C]hydroxyproline synthesis. In control rat liver, the amount of free and small peptide-bound [14C]hydroxyproline synthesized was 13.1 +/- 2.6 10(-4) x dpm/g liver/3 hr. In the CCl4-treated rat liver, where the hepatic hydroxyproline content was increased 4.6-fold, the protein-bound [14C]hydroxyproline synthesis was significantly increased 1.5-fold, but free and small peptide-bound [14C]hydroxyproline synthesis was decreased into 70%. There was a significant inverse correlation between free and small peptide-bound [14C]hydroxyproline synthesis, and hepatic hydroxyproline content. These results suggest that the combination of an increase in collagen synthesis and a decrease in free and small peptide-bound [14C]hydroxyproline synthesis contributes to rapid accumulation of collagen in hepatic fibrosis.
为阐明肝纤维化过程中游离及小肽结合型羟脯氨酸的合成过程，我们测定了大鼠肝切片中67%乙醇可溶部分的[14C]羟脯氨酸体外合成量，以及肝蛋白结合型[14C]羟脯氨酸的合成量。在对照大鼠肝脏中，合成的游离及小肽结合型[14C]羟脯氨酸量为13.1±2.6×10(-4)×dpm/g肝脏/3小时。在CCl4处理的大鼠肝脏中，肝羟脯氨酸含量增加了4.6倍，蛋白结合型[14C]羟脯氨酸合成显著增加了1.5倍，但游离及小肽结合型[14C]羟脯氨酸合成降至70%。游离及小肽结合型[14C]羟脯氨酸合成与肝羟脯氨酸含量之间存在显著的负相关。这些结果表明，胶原合成增加与游离及小肽结合型[14C]羟脯氨酸合成减少共同作用，导致肝纤维化过程中胶原的快速积累。
