牛磺熊去氧胆酸和牛磺-β-鼠胆酸通过降低肝细胞内牛磺鹅去氧胆酸含量发挥细胞保护作用。

Tauroursodeoxycholate and tauro-beta-muricholate exert cytoprotection by reducing intrahepatocyte taurochenodeoxycholate content.

作者信息

Ohiwa T, Katagiri K, Hoshino M, Hayakawa T, Nakai T

机构信息

First Department of Internal Medicine, Nagoya City University, Medical School, Japan.

出版信息

Hepatology. 1993 Mar;17(3):470-6.

PMID:8383089

Abstract

Cytoprotection by tauroursodeoxycholic acid and tauro-beta-muricholic acid against taurochenodeoxycholic acid-induced toxicity was examined with reference to intracellular bile acid content in primary cultured rat hepatocytes. In comparison with levels in the group administered taurochenodeoxycholic acid 1 mmol/L alone, lactate dehydrogenase levels in the culture medium decreased significantly in groups simultaneously administered taurochenodeoxycholic acid 1 mmol/L and tauroursodeoxycholic acid 0.5 to 2 mmol/L or tauro-beta-muricholic acid. Results of the trypan blue uptake test indicated that the lactate dehydrogenase release was indeed caused by cell damage. After the administration of tauroursodeoxycholic acid 2 mmol/L or tauro-beta-muricholic acid 2 mmol/L, intracellular taurochenodeoxycholic acid content was consistently reduced to half of that after administration of taurochenodeoxycholic acid alone. Simultaneous administration of dibutyl cyclic AMP also reduced intracellular taurochenodeoxycholic acid content and lactate dehydrogenase release. Being rinsed with tauroursodeoxycholic acid and tauro-beta-muricholic acid after being precultured in taurochenodeoxycholic acid 1 mmol/L also markedly reduced their taurochenodeoxycholic acid content. Taurocholic acid caused limited reduction of intracellular taurochenodeoxycholic acid but not suppression of lactate dehydrogenase release. Taurodehydrocholic acid showed no reduction of taurochenodeoxycholic acid content and no decrease of lactate dehydrogenase release. Although only small amounts of tauroursodeoxycholic acid or tauro-beta-muricholic acid were found to accumulate in hepatocytes, taurocholic acid increased as if replacing taurochenodeoxycholic acid. The results suggest that tauroursodeoxycholic acid or tauro-beta-muricholic acid may exert cytoprotective effects by lowering intracellular taurochenodeoxycholic acid levels associated with their optimal hydrophilicity.

摘要

参照原代培养大鼠肝细胞内胆汁酸含量，研究了牛磺熊去氧胆酸和牛磺-β-鼠胆酸对牛磺鹅去氧胆酸诱导毒性的细胞保护作用。与单独给予1 mmol/L牛磺鹅去氧胆酸组相比，同时给予1 mmol/L牛磺鹅去氧胆酸和0.5至2 mmol/L牛磺熊去氧胆酸或牛磺-β-鼠胆酸的组中，培养基中的乳酸脱氢酶水平显著降低。台盼蓝摄取试验结果表明，乳酸脱氢酶释放确实是由细胞损伤引起的。给予2 mmol/L牛磺熊去氧胆酸或2 mmol/L牛磺-β-鼠胆酸后，细胞内牛磺鹅去氧胆酸含量持续降至单独给予牛磺鹅去氧胆酸后的一半。同时给予二丁酰环磷腺苷也降低了细胞内牛磺鹅去氧胆酸含量和乳酸脱氢酶释放。在1 mmol/L牛磺鹅去氧胆酸中预培养后用牛磺熊去氧胆酸和牛磺-β-鼠胆酸冲洗，也显著降低了它们的牛磺鹅去氧胆酸含量。牛磺胆酸使细胞内牛磺鹅去氧胆酸含量有限降低，但未抑制乳酸脱氢酶释放。牛磺去氢胆酸未降低牛磺鹅去氧胆酸含量，也未使乳酸脱氢酶释放减少。虽然仅发现少量牛磺熊去氧胆酸或牛磺-β-鼠胆酸在肝细胞中蓄积，但牛磺胆酸增加，似乎取代了牛磺鹅去氧胆酸。结果表明，牛磺熊去氧胆酸或牛磺-β-鼠胆酸可能通过降低与它们最佳亲水性相关的细胞内牛磺鹅去氧胆酸水平发挥细胞保护作用。