体外鼠肝灌注时胆酸对胆汁、谷氨酸脱氢酶和线粒体膜稳定性的影响(英)

Influence of bile acids on bile secretion, glutamate dehydrogenase and mitochondria membrane stability in perfused rat liver in situ

目的 :探讨熊脱氧胆酸 (U DCA)和鹅脱氧胆酸 (CDCA)对胆汁分泌、谷氨酸脱氢酶 (GL DH)和线粒体膜结构的作用 ,以及 U DCA 的线粒体膜保护作用。 方法 :应用离体大鼠肝灌注技术 ,0 .1～ 0 .5 mm ol/ L 胆酸灌注鼠肝 ,测定胆汁分泌及GL DH释放。分离鼠肝线粒体 ,自旋标记物插入线粒体膜 ,研究膜结构变化。结果 :CDCA(0 .1、0 .3、0 .5 m mol/ L)可使胆汁分泌分别减少 12 %、77.2 5 %和 78.98% ,明显增加 GL DH释放达 3、9和 12倍 ,并增加线粒体膜的流动性 ;UDCA在 0 .3、0 .5mm ol/ L 时可增加胆汁分泌达 1.8倍和 1.9倍 ,不影响 GL DH和线粒体膜结构。预灌注 UDCA可部分缓解 CDCA引起的GL DH释放和胆汁分泌减少 ,稳定线粒体膜结构。结论 :CDCA破坏线粒体膜和引起肝功能减退。U DCA可改善胆汁分泌 ,部分阻止 CDCA对线粒体的损害。低浓度 CDCA不损害肝功能。

Objective:To investigate whether enzyme release caused by chenodeoxycholic acid (CDCA) can be prevented by ursodeoxycholic acid (UDCA),and to study the effects of bile acids on bile secretion, glutamate dehydrogenase (GLDH) release and mitochondrial membrane structure. Methods: Totally 0.1 0.5 mmol/L bile acids were perfused into rat livers for 120 min. The bile duct was cannulated for collection of bile flow and GLDH was determined. Intact mitochondria were isolated and mitochondrial suspension was detected with electron paramagnetic resonance spectroscopy (EPR) for membrane mobility and polarity values. Results: Compared with control, CDCA at 0.1,0.3, 0.5 mmol/L decreased the bile flow by 12%, 77.25% and 78.98%, and enhanced GLDH release by 3, 9 and 21 times, respectively. It also increased the mobility of 4 maleimido TEMPO spin label and the polarity of hydrophobic membrane interior. UDCA increased bile flow by 1.8 times at 0.3 mmol/L and 1.9 times at 0.5 mmol/L. It did not influence enzyme release and membrane structure. Prior infusion with UDCA (0.1 mmol/L) for 30 min followed by combination of UDCA and CDCA improved bile secretion, delayed enzyme release and partly prevented the membrane lesion caused by CDCA compared with CDCA alone. Conclusion:CDCA can damage mitochondrial membrane structure and result in liver dysfunction. UDCA improves secretion of bile and partly prevents liver mitochondrial lesion against CDCA. Low concentration of CDCA does not damage the liver function.