Korolenko T A, Savchenko N G, Yuz'ko Ju V, Alexeenko T V, Sorochinskaya N V
Institute of Physiology, Siberian Division of the Russian Academy of Medical Sciences, Novosibirsk, Russia.
Bull Exp Biol Med. 2008 May;145(5):560-3. doi: 10.1007/s10517-008-0147-x.
Lysosomal enzyme activity in the bile and blood serum was compared in mice with experimental intrahepatic cholestasis induced by alpha-naphthyl isothiocyanate and Triton WR 1339. Triton WR 1339 increases the synthesis of cholesterol (fatty acid precursor) in liver cells. The development of intrahepatic cholestasis was confirmed by the increase in activities of alkaline phosphatase and gamma-glutamyltransferase in blood serum. Administration of Triton WR 1339 in a dose of 100 mg/100 g was followed by a 10-fold increase in beta-galactosidase activity (hepatocyte lysosomal enzyme) in the bile, but not in the serum of mice. beta-Galactosidase activity significantly increased in the bile, but decreased in the serum of mice after treatment with a-naphthyl isothiocyanate in a dose of 200 mg/kg. Our results indicate that intrahepatic cholestasis is manifested in increased secretion of lysosomal glycosidases into the bile. Bile components can aggravate damage to liver cells by affecting the processes of hepatocyte apoptosis and necrosis.
在由异硫氰酸α-萘酯和曲拉通WR 1339诱导的实验性肝内胆汁淤积小鼠中，比较了胆汁和血清中的溶酶体酶活性。曲拉通WR 1339可增加肝细胞中胆固醇（脂肪酸前体）的合成。血清中碱性磷酸酶和γ-谷氨酰转移酶活性的增加证实了肝内胆汁淤积的发展。以100 mg/100 g的剂量给予曲拉通WR 1339后，小鼠胆汁中β-半乳糖苷酶活性（肝细胞溶酶体酶）增加了10倍，但血清中未增加。以200 mg/kg的剂量用异硫氰酸α-萘酯处理后，小鼠胆汁中β-半乳糖苷酶活性显著增加，但血清中活性降低。我们的结果表明，肝内胆汁淤积表现为溶酶体糖苷酶向胆汁中的分泌增加。胆汁成分可通过影响肝细胞凋亡和坏死过程加重对肝细胞的损伤。
