大鼠心脏缺血-再灌注损伤对心肌L-Arg/NO途径的影响

EFFECTS OF MYOCARDIAL ISCHEMIA REPERFUSION INJURY ON L ARGININE/NITRIC OXIDE SYSTEM IN RAT HEART

为探讨大鼠心脏缺血再灌注损伤（ＩＲＩ）期间一氧化氮（ＮＯ）生成增加的环节和过程。本实验用离体灌流大鼠心脏，预灌流１５ｍｉｎ，停灌４５ｍｉｎ，取３０ｍｌＫＨ液循环灌流１５ｍｉｎ，观察冠脉流出液中细胞胞浆酶（ＬＤＨ）、蛋白质、肌红蛋白漏出量和ＮＯ－２含量、心肌组织ＮＯＳ活性、Ｌ精氨酸（ＬＡｒｇ）转运的改变。结果显示，心脏ＩＲＩ后，冠脉流出液中ＬＤＨ活性、蛋白质和肌红蛋白量较对照组分别增加４１，５４和１倍（均Ｐ＜００１）。ＮＯ－２含量增加１２倍（Ｐ＜００１）。心肌组织ｔＮＯＳ活性、ｉＮＯＳ活性和ｃＮＯＳ活性分别增加４８２％、４３２％和５２１％（均Ｐ＜００１）。ＮＯ－２含量与心肌组织ｉＮＯＳ活性呈正相关，（ｒ＝０７９４２，Ｐ＜００１）。心肌组织ＬＡｒｇ转运呈现高、低亲和两种方式。ＩＲＩ组心肌ＬＡｒｇ转运能力增强，最大转运速率（Ｖｍａｘ）较对照组升高４８％（低亲和，Ｐ＜００５）和２倍（高亲和，Ｐ＜００１）；低亲和Ｋｍ值降低４７４％（Ｐ＜００５），高亲和Ｋｍ值改变无统计学意义。ＬＡｒｇ转运高、低亲和转运载体的Ｖｍａｘ与ｉＮＯＳ活性、ＮＯ－２含量均呈高度正相关关系。结果提示：心脏?

Ischemia reperfusion injury(IRI) model of rat heart was prepared by preperfusion for 15 min, then a suspension for 45 min and recycling reperfusion for 15 min with 30 ml KH buffer. The leakage of lactate dehydrogenase(LDH), protein, myoglobine and nitrite (NO - 2) in the circular perfusion fluid were measured. Myocardial nitric oxide synthase(NOS) activity and L arginine transport were observed. In the IR group,the leakage of LDH, protein, myoglobine and NO - 2 were increased respectively by 4 1, 5 4, 1 and 1 2 times( P <0 01) and NOS(tNOS, iNOS, cNOS) activity by 48 2%, 43 2%and 52 1%, ( P <0 01, respectively) as compared with the control group. L arginine transport might be mediated by either high or low affinity transport system in cardiac tissue. In the IR group, L arginine transport increased significantly with the V max being increased by 48% and 2 times respectively for the low affinity and the high affinity transport as compared with control. Michaelis constant (km) was decreased by 47 4% for low affinity transport ( P <0 05), but not significantly changed for the high affinity transport. These results suggest that the increase of nitric oxide generation might result from the increased myocardial NOS activity and L arginine transport during IRI.