L-硝基精氨酸甲酯对大鼠肢体缺血再灌注继发心肌损伤的影响

Effect of L-NAME on myocardium in rat which suffered from limb ischemia-reperfusion

目的研究L-硝基精氨酸甲酯(L-NAME)对肢体缺血再灌注(LIR)后心肌损伤的影响。方法止血带法制作LIR大鼠模型,随机分成缺血再灌注组(A组)、L-NAME处理组(B组)、对照组。B组在再灌注前经静脉给予L-NAME 10 mg/kg,A组和对照组静注等量生理盐水。观察三组心肌组织丙二醛(MDA)、髓过氧化物酶(MPO)、肿瘤坏死因子-α(TNF-α)、血浆磷酸激酶(CK)、磷酸激酶同工酶(CK-MB)及NO含量;心脏插管检测平均动脉压(MAP)、左心室收缩压(LVSP)、收缩期左室内压上升最大速率(DP/DTm ax)、舒张期左室内压下降最大速率(-DP/DTm ax);光镜下观察心肌组织的形态学变化。结果A、B组心肌组织MDA、MPO和TNF-α含量增加(P<0.01,<0.05),血浆CK、CK-MB及NO水平升高(P<0.01),MAP、LVSP等血流动力学指标下降,镜下可见心肌细胞水肿等组织损伤征象。静脉给予L-NAME后,心肌组织MDA、MPO含量增加和血浆CK、CK-MB及TNF-α升高更加明显(P<0.01或P<0.05),NO、DP/DTm ax、-DP/DTm ax显著下降(P<0.01),光镜下心肌组织的损伤性表现加重。结论L-NAME可能通过抑制体内NO生成而加重大鼠LIR继发的心肌损伤。

Objective To investigate the effect of Nω-nitro-L-arginine methyl ester （L-NAME） on myocardium in rat which suffered from limb ischemia-reperfusion. Methods Models of limb ischemia reperfusion were made by tourniquet methods, L-NAME （10mg/kg） was given by vein to some of those animals before reperfusion. We meassured the contents of malondialdehyde（MDA） , myeloperoxidase（MPO） and tumour necrosis factor（TNF-cx） in myocardial tissue,, determined the levels of creatine kinase（CK） ,creatine kinase MB isoenzyme（CK-MB） and nitric oxide（NO） in plasma. The mean arterial pressure （MAP） ,left venteieular systolic pressure （LVSP） , maximal rise rate of left venteicular pressure （DP/DTmax） and the maximal fall rate of left venteicular pressure（ - DP/DTmax） were monitored. We also observed morphologic changes of myocardium. Results It was found that after rats＇ limbs suffering from isehemia-reperfusion, levels of MDA, MPO and TNF-α in myocardium, CK,CK-MB and NO in plasma increased in different degree（P 〈 0.01, 〈 0.05 ）. MAP, LVSP, DP/DTmax and - DP/DTmax decreased obviously. All of these differentiations were significant. Conclusions L-NAME can aggravate the myocardium injury that followed limb ischemia-repeffusion ,the effect,may be related to inhibiting the produce of NO in body.