Umezu K, Yuasa S, Sudoh A, Inagaki M
Nihon Yakurigaku Zasshi. 1986 Mar;87(3):291-300. doi: 10.1254/fpj.87.291.
Liver cirrhosis was induced by consecutive CCl4-treatment of rats (0.5 ml/kg, s.c., 2 times/week) to investigate the effect of TRQ on the acceleration of fibrosis in the liver. An increase of hydroxyproline content in the liver of rats began 12 weeks after the CCl4 treatment and a 1.9-fold increase was observed at week 14 compared with non-CCl4 treated rats. Histamine in the liver increased about 2 times at week 14. Increased numbers of mast cells were seen in the area of proliferated collagen fiber in the liver under microscopic observation, and also a good correlation was recognized between the number of mast cells and the progression of fibrosis. An administration of TRQ to the rats for 2 weeks from week 13 resulted in significant suppression of both the increase in hydroxyproline and histamine in the liver dose-dependently compared with the CCl4 control group. Both progression of collagen and increase in mast cell numbers were also suppressed by TRQ dose-dependently under histopathological observation; at the same time the decrease in mast cells was recognized to correspond to the decrease in hydroxyproline and histamine in the liver. Thus, it was suggested that increased mast cells participated in the biosynthesis of collagen. Though the elevated serum transaminases, alkaline phosphatase and leucine amino peptidase were also suppressed by TRQ administration, the protein biosynthesis activity of the liver and lowered serum total cholesterol were not improved as much as the other parameters. From these results, it was shown that TRQ was especially and remarkably effective in suppressing the acceleration of fibrosis, and one of the pharmacological mechanisms of this action may be ascribed to the inhibitory effect of TRQ on the activation of mast cells by some stimulants.
通过连续用四氯化碳处理大鼠（0.5毫升/千克，皮下注射，每周2次）诱导肝硬化，以研究TRQ对肝脏纤维化加速的影响。四氯化碳处理12周后，大鼠肝脏中的羟脯氨酸含量开始增加，与未用四氯化碳处理的大鼠相比，在第14周时观察到增加了1.9倍。肝脏中的组胺在第14周时增加了约2倍。在显微镜下观察发现，肝脏中增殖的胶原纤维区域肥大细胞数量增加，并且肥大细胞数量与纤维化进展之间存在良好的相关性。从第13周开始给大鼠服用TRQ 2周，与四氯化碳对照组相比，肝脏中羟脯氨酸和组胺的增加均受到剂量依赖性的显著抑制。在组织病理学观察下，TRQ也剂量依赖性地抑制了胶原的进展和肥大细胞数量的增加；同时，肥大细胞的减少与肝脏中羟脯氨酸和组胺的减少相对应。因此，提示肥大细胞增多参与了胶原的生物合成。虽然TRQ给药也抑制了血清转氨酶、碱性磷酸酶和亮氨酸氨基肽酶的升高，但肝脏的蛋白质生物合成活性和降低的血清总胆固醇并未像其他参数那样得到明显改善。从这些结果可以看出，TRQ在抑制纤维化加速方面特别有效，这种作用的药理机制之一可能归因于TRQ对某些刺激物激活肥大细胞的抑制作用。
