氨基胍对内毒素休克大鼠肝损伤的保护作用研究

An Experimental Study on the Protective Role of Aminoguanidine on Liver Injury in Endotoxic Shock

目的 探讨诱导型一氧化氮合酶 (iNOS)抑制剂氨基胍对内毒素休克大鼠肝脏的组织学和超微结构的影响。方法 取雄性Wistar大鼠 2 4只 ,随机分为正常对照组、内毒素对照组和氨基胍治疗组 ,每组各 8只。用大肠杆菌内毒素 (LPS)复制大鼠内毒素性休克模型 ,氨基胍治疗组采用氨基胍治疗。观察并比较三组大鼠肝脏的组织学、超微结构及其血浆一氧化氮 (NO)含量的变化。结果 光镜下可见 ,内毒素组肝组织有散在小脓肿灶形成 ,肝细胞坏死 ,中性白细胞浸润 ,而氨基胍治疗组的肝组织受损程度较轻。电镜下可见 ,内毒素组的肝细胞核出现融解性空斑 ,线粒体肿胀和线粒体嵴数量减少 ,而氨基胍则对肝脏的结构起到一定的保护作用。内毒素对照组血浆NO水平明显高于正常对照组 ,给予氨基胍治疗后血浆NO水平明显下降 ,但仍高于正常对照组。结论 氨基胍通过选择性抑制iNOS活性 ,抑制了大鼠内毒素休克时过量的NO的产生 ,保护了肝脏的功能 ,具有潜在的临床应用价值 ,值得更深入地研究。

Objective To study the effects of aminoguanidine (AG), a selective inhibitor of inducible nitric oxide synthase (iNOS) on the pathological changes of liver tissues and ultrastructural changes of liver cells in rodent model of endotoxic shock. Methods Twenty-four male Wistar rats were randomly divided into normal control group,lipopolysaccharide (LPS) control group and AG treatment group, each group had 8 rats. Rats were challenged by E.coli LPS to set up the model of endotoxic shock, AG group were treated by aminoguanidine. The pathological and ultrastructural changes of liver tissues and plasma NO contents of three groups were observed and compared. Results Light microscopy revealed that many tiny abscesses scattered in liver tissue in LPS group, accompanied by necrosis of liver cells and neutrophils infiltration, while liver injuries of AG group were much slighter than that in LPS group. Electron microscopy revealed that there were dissolved plaques in hepatocyte nuclears, swelling of mitochondria, decreasing in number of mitochondrial ridges, while AG play a protective role to nuclears and mitochondria of hepatocytes. The plasma NO levels of LPS control group were higher than that of normal control group, and plasma NO levels decreased significantly after AG treatment, but still higher than that of normal control group. Conclusion Aminoguanidine selectively inhibits iNOS activity and prevents the overproduction of NO induced by iNOS, thus attenuates the damages of liver structure induced by NO. This method has potential value in clinical application, which deserves more deep research.