Yuasa S, Sudoh A, Toshida K, Takechi M, Umezu K
Nihon Yakurigaku Zasshi. 1985 Apr;85(4):249-57. doi: 10.1254/fpj.85.249.
Rats were treated with CCl4 for 12 weeks to induce chronic liver injury. An administration of tritoqualine (TRQ) to rats was begun 3 weeks after the first CCl4 treatment, and the therapeutic effect of TRQ on this model was investigated. On the 12th week after CCl4 treatment, a marked increase in content of hydroxyproline and histamine in the liver was found. In addition, increased fibrosis around Glisson's sheath was observed under microscopic observation. The increase in these biochemical parameters was suppressed significantly in the rats administered TRQ at doses of 25-100 mg/kg. The histopathological observation demonstrated the suppression of the formation of pseudolobules with fibrinogenesis in the liver of TRQ administered rats. In addition, there was a noticeable improvement in the activity of the liver protein synthesis in the TRQ administered rats when the parameters that represented the hepatic functions were measured. Glutamic oxaloacetic transaminase in the serum of TRQ-administered rats also decreased significantly, compared with the CCl4 treated control rats. From these results, TRQ was shown to exhibit a marked therapeutic effect on liver damage accompanied by chronically accelerated fibrosis in rats which have been treated with CCl4 for 12 weeks.
用四氯化碳(CCl4)处理大鼠12周以诱导慢性肝损伤。在首次CCl4处理3周后开始给大鼠施用曲托喹啉(TRQ),并研究TRQ对该模型的治疗效果。在CCl4处理后的第12周,发现肝脏中羟脯氨酸和组胺含量显著增加。此外,在显微镜观察下观察到肝门管区周围纤维化增加。在以25-100mg/kg剂量施用TRQ的大鼠中,这些生化参数的增加被显著抑制。组织病理学观察表明,在施用TRQ的大鼠肝脏中,假小叶形成和纤维蛋白生成受到抑制。此外,在测量代表肝功能的参数时,施用TRQ的大鼠肝脏蛋白质合成活性有明显改善。与CCl4处理的对照大鼠相比,施用TRQ的大鼠血清中的谷氨酸草酰乙酸转氨酶也显著降低。从这些结果来看,TRQ对用CCl4处理12周的大鼠伴随慢性加速纤维化的肝损伤显示出显著的治疗效果。