Šmíd V, Petr T, Váňová K, Jašprová J, Šuk J, Vítek L, Šmíd F, Muchová L
Institute of Medical Biochemistry and Laboratory Diagnostics, First Faculty of Medicine, Charles University in Prague and General University Hospital in Prague, Czech Republic.
Folia Biol (Praha). 2016;62(4):148-59. doi: 10.14712/fb2016062040148.
Bile acids have been implicated in cholestatic liver damage, primarily due to their detergent effect on membranes and induction of oxidative stress. Gangliosides can counteract these harmful effects by increasing the rigidity of the cytoplasmic membrane. Induction of haem oxygenase (HMOX) has been shown to protect the liver from increased oxidative stress. The aim of this study was to determine the changes in the synthesis and distribution of liver gangliosides following bile duct ligation (BDL), and to assess the effects of HMOX both on cholestatic liver injury and ganglioside metabolism. Compared to controls, BDL resulted in a significant increase in total as well as complex gangliosides and mRNA expression of corresponding glycosyltransferases ST3GalV, ST8SiaI and B3GalTIV. A marked shift of GM1 ganglioside from the intracellular compartment to the cytoplasmic membrane was observed following BDL. Induction of oxidative stress by HMOX inhibition resulted in a further increase of these changes, while HMOX induction prevented this effect. Compared to BDL alone, HMOX inhibition in combination with BDL significantly increased the amount of bile infarcts, while HMOX activation decreased ductular proliferation. We have demonstrated that cholestasis is accompanied by significant changes in the distribution and synthesis of liver gangliosides. HMOX induction results in attenuation of the cholestatic pattern of liver gangliosides, while HMOX inhibition leads to the opposite effect.
胆汁酸与胆汁淤积性肝损伤有关，主要是因为其对细胞膜的去污剂作用以及诱导氧化应激。神经节苷脂可通过增加细胞质膜的刚性来抵消这些有害作用。已证明诱导血红素加氧酶（HMOX）可保护肝脏免受氧化应激增加的影响。本研究的目的是确定胆管结扎（BDL）后肝脏神经节苷脂合成和分布的变化，并评估HMOX对胆汁淤积性肝损伤和神经节苷脂代谢的影响。与对照组相比，BDL导致总神经节苷脂以及复合神经节苷脂和相应糖基转移酶ST3GalV、ST8SiaI和B3GalTIV的mRNA表达显著增加。BDL后观察到GM1神经节苷脂从细胞内区室向细胞质膜的明显转移。HMOX抑制诱导氧化应激导致这些变化进一步增加，而HMOX诱导可防止这种效应。与单独BDL相比，HMOX抑制与BDL联合显著增加了胆汁梗死的数量，而HMOX激活减少了小胆管增生。我们已经证明胆汁淤积伴随着肝脏神经节苷脂分布和合成的显著变化。HMOX诱导导致肝脏神经节苷脂胆汁淤积模式减弱，而HMOX抑制则导致相反的效果。
