氧自由基和一氧化氮在急性肾功能衰竭诱发多器官功能障碍综合征中的作用

Effects of free oxygen radical and nitric oxide in multiple organ dysfunction syndrome induced by acute renal failure

目的 观察急性肾功能衰竭(ARF)家兔肝、肺、心、肾匀浆氧自由基、一氧化氮(NO)及一氧化氮合酶(NOS)的变化,探讨ARF诱发多器官功能障碍综合征(MODS)的机制。方法 60只家兔随机均分为4组(n=15)。ARF模型Ⅰ组皮下注射质量分数为1％的HgCl2(1.3 ml／kg);ARF模型Ⅱ组肌肉注射体积分数为50％的甘油(10 ml／kg);以等量生理盐水分别代替HgCl2和甘油作为对照Ⅰ和Ⅱ组。24 h后,自动物颈总动脉放血备检,并选择固定位置,取肝、肺、心、肾组织制备体积分数为10％的匀浆。经Aeroset型全自动生化分析仪测定血清尿素氮、肌酐,检测各脏器组织匀浆超氧化物歧化酶(SOD)、丙二醛(MDA)、NO含量及NOS、诱导型NOS(iNOS)活性。结果 与相应对照组比较,ARF模型Ⅰ、Ⅱ组心肌组织匀浆SOD活性下降、MDA含量升高(P均<0.05),ARF模型Ⅰ、Ⅱ组心肌组织匀浆NO含量升高,NOS及iNOS活性增强(P<0.05或P<0.01);肝、肺组织匀浆的上述指标变化无统计学意义(P均>0.05)。ARF模型Ⅰ、Ⅱ组血清NO含量及NOS、iNOS活性分别高于相应对照组(P<0.05或P<0.01),肾组织匀浆NO含量显著高于相应对照组(P均<0.01)。结论 ARF可致心肌损伤,诱发MODS的发生,其机制与氧自由基损伤及NO升高有关。NO在ARF发病过程中发挥保护及损伤的双重作用。

Objective To observe the changes in free oxygen redical and nitric oxide (NO) in the liver, lung, and heart homogenate in rabbits with acute renal failure (ARF), and inquire into the mechanism of multiple organ dysfunction syndrome (MODS) subsequent to ARF. Methods Sixty rabbits were randomly divided into four groups (n=15 in each group). In the group I ARF was reproduced by hypodermic injection of 1% HgCl2 in a dose of 1. 3 ml/kg, and in group Ⅰ ARF was reproduced by intramuscular injection of 50% glycerin in a dose of 10 ml/kg. In the control groups Ⅰ and Ⅱthe rabbits received an equal volume of normal saline. After 24 hours, blood samples were obtained from all the rabbits, and the liver, lung and heart were harvested and 10% homogenates were made. The blood urea nitrogen and serum creatinine were determined by automatic biochemical analyzer(Aeroset), superoxide dismutase (SOD), malondialdehyde (MDA), NO, nitric oxide synthase (NOS), and inducible nitric oxide synthase (iNOS) in tissue homogenate were also determined. Results It showed that SOD activity was significantly lowered and the MDA, NO, NOS and iNOS were significantly increased in heart homogenate of ARF groups Ⅰ and Ⅱ compared with control group Ⅰ and Ⅱ (P<0.01 or P<0. 05). But these indexes in the liver and lung homogenates were not significanlty different between the groups(all P>0.05). The levels of NO, NOS and iNOS in serum of ARF groups Ⅰ and Ⅱ were significantly increased compared with control group Ⅰ and Ⅱ (P<0. 05 or P<0.01), and the NO contents in renal homogenate of ARF groups Ⅰ and Ⅱ were significantly increased compared with control group Ⅰ and Ⅱ (P<0.01). Conclusion There is sign of damage of the myocardium in ARF, resulting in MODS. Its passible pathogenic mechanism might be attributable to free oxygen redical injury and increase in NO production. NO plays a dual role of protection and damage in the pathogenesis of ARF.