一氧化氮、内皮素-1在内毒质所致肝脏损伤中的作用机制研究

EFFECTS OF NITRIC OXIDE AND ENDOTHELIN 1 ON HEPATIC DAMAGE INDUCED BY ENDOTOXIN IN RATS

目的 探讨一氧化氮 (NO)和内皮素 -1(ET-1)在内毒素所致肝脏损伤中的作用机制。方法 Waster大鼠 40只随机分成对照组、内毒素组、内皮素受体拮抗剂组和左旋精氨酸组 ,观察各组大鼠血浆 NO和 ET-1水平、肝脏功能变化 ,在光镜下观察肝细胞损伤程度 ,在电镜下观察肝脏超微结构改变。结果 大鼠投予内毒素 12 h后 ,血浆 NO和 ET-1水平明显下升 ,血浆转氨酶水平增加。肝细胞明显水肿、变性和坏死 ,肝筛的数量和直径明显减少。左旋精氨酸和内皮素受体损坏抗剂均能明显减轻肝脏功能和结构的损伤。结论 在内毒素所致肝损伤中 ,NO起保护性作用 ,而 ET-1则起促进作用 。

Objective To observe the effects of nitric oxide(NO) and endothelin 1 (ET 1) on hepatic damage induced by endotoxin.Methods Forty Wistar rats were randomized into the control?endotoxin?endotoxin plus CYCLO(ETRA antagonist) and endotoxin plus L arg groups killed in the 12th hour.All these chemicals (except for L arg injected from abdominal cavity)were injected from left femoral vein.The contents of plasma NO and ET 1 were determined.Plasma transaminases were also measured.The degree of hepatocytic necrosis was observed by light microscope and the ultrastructural changes of liver sieve were observed by electron microscope.Results In endotoxemia,the contents of plasma ET 1 and NO increased significally compared with those of control group.Plasma ALT and AST concentrations were also markedly increased.The serious hepatocytic degeneration?swelling and necrosis were observed in endotox in group.The diameter and number of fenestrate on the contracted hepatic sinusoid endothelium cells were greatly decreased.Treated with L arg of CYCLO could partially alleviate all these pathological chages noted above.Conclusion ET 1 which leads to liver sieve's defenestration might contribute to hepatic damange induced by endotoxin,while NO plays a protective role by keeping liver sieve's open.