Nakashima T, Shima T, Sakamoto Y, Nakajima T, Seto Y, Sano A, Iwai M, Okanoue T, Kashima K
Third Department of Internal Medicine, Kyoto Prefectural University of Medicine, Japan.
J Hepatol. 1993 Apr;18(1):74-9. doi: 10.1016/s0168-8278(05)80012-1.
In cholestasis and obstructive jaundice, hepatic bile acids and taurine content increase significantly and bile acids change in compositions. For example, increases in cholic acid, beta-muricholic acid and taurine-conjugated bile acids occur in rats. In this study, to clarify the significance of changes in bile acid composition in obstructive jaundice, the effects of various bile acids and taurine on the fluidity of the hepatic microsomal membrane were studied by the electron spin resonance spin-label method in normal and bile duct-ligated (for 10 days) rats. The flow properties (order parameter) of the shallow and deep layers of the membrane were determined with 5- and 12-doxyl stearic acid, respectively. Bile acids mainly affected the fluidity of the shallow membrane layer. The fluidity of the hepatic microsomal membrane was decreased in bile duct-ligated rats. Conjugated cholic acid (taurine-conjugated cholic acid, glycine-conjugated cholic acid and non-conjugated beta-muricholic acid exerted effects that increased fluidity in comparison with non-conjugated cholic acid and chenodeoxycholic acid, a precursor of beta-muricholic acid. Taurine had no clear effect on fluidity. In conclusion, cholic acid conjugation and beta-muricholic acid formation may be mechanisms which protect against the decrease in lipid fluidity of hepatic biomembranes in cholestasis or obstructive jaundice. Taurine may also affect fluidity through the formation of taurine-conjugated bile acids.
在胆汁淤积和梗阻性黄疸中,肝脏胆汁酸和牛磺酸含量显著增加,且胆汁酸组成发生变化。例如,大鼠体内胆酸、β-鼠胆酸和牛磺酸结合型胆汁酸增加。在本研究中,为阐明梗阻性黄疸中胆汁酸组成变化的意义,采用电子自旋共振自旋标记法,研究了正常大鼠和胆管结扎(10天)大鼠中各种胆汁酸和牛磺酸对肝微粒体膜流动性的影响。分别用5-和12-硬脂酸氧基硬脂酸测定膜浅层和深层的流动特性(序参数)。胆汁酸主要影响膜浅层的流动性。胆管结扎大鼠的肝微粒体膜流动性降低。与未结合胆酸和β-鼠胆酸的前体鹅去氧胆酸相比,结合胆酸(牛磺酸结合胆酸、甘氨酸结合胆酸和未结合β-鼠胆酸)可增加膜的流动性。牛磺酸对膜流动性无明显影响。总之,胆酸结合和β-鼠胆酸形成可能是防止胆汁淤积或梗阻性黄疸时肝生物膜脂质流动性降低的机制。牛磺酸也可能通过形成牛磺酸结合型胆汁酸来影响膜流动性。