肾缺血预处理增强心脏的电稳定性

1、肾缺血预处理增强心脏的电稳定性摘要目的：研究肾缺血预处理(IPC)对心脏电稳定性的影响和机理。方法：24只大耳白兔随机分为对照组、肾缺血再灌流(I/R)组和肾IPC+I/R组。观察肾再灌流24 h时及用垂体后叶素(Pt)和肾上腺素(Adr)后的心电动态变化以及血中一氧化氮(NO)和心肌中丙二醛(MDA)的浓度改变。结果：用Pt和Adr后，肾I/R组缺血性ST段抬高和心律失常发生率同肾IPC+I/R组差异显著；肾IPC+I/R组NO代谢物升高和MDA降低同I/R组差异显著(P0.05)；除MDA外，上述指标在肾IPC+I/R组 与对照组间差异无显著。结论：肾IPC通过减轻心肌缺血性改变使心脏电稳

2、定性增强；NO可能通过增加氧自由基的清除和扩血管效应而参与此作用。主题词局部缺血；肾；心脏；再灌注 The increase in electrocardiac stability by kidney ischemic preconditioningFENG Zhi-Chiang, RAN Bin, ZHANG Chun-Lai, PAN Chiang-Wen,LI Li-Hua, LIn Hai-Ying, LI Xian-HuaDepartment of Physiology, Luzhou Medical College, Luzhou(646000)Abstract AIM: The

3、effect of kidney ischemic preconditioning on electrocardiac stability and its mechanism were studied in the article. METHODS：24 adult Japanese white rabbits were randomly divided into three groups: control group (n=6), left renal artery (LRA) received no clamping; ischemic reperfusion (I/R) group (n

4、=9),LRA received clamping for 1 hour followed by 24 hours of reperfusion; ischemic preconditioning (IPC) and I/R group (n=9), LRA received clamping for 5 minutes followed by 10 minutes of reperfusion, which was done repeatedly 3 times, then, do the same process again as in I/R group. The dynamic cha

5、nges of electrocardiogram were observed at 24th hour of reperfusion and after intravenous pituitrin (Pt) 2Ukg-1 for 10 minutes and adrenalin (Adr) 0.03 mgkg-1 for 15 minutes. Concentration of nitric oxide (NO) in blood and molonyldehyde (MDA) content in cardiac tissue were chected in three groups. R

6、ESULTS：There was a considerable difference in the ischemic ST segment elevation and also in arrhythmogenic rate between I/R group (0.2700.160 mV, 88.89%) and IPC+I/R group (0.0900.300 mV, 22.22%) after Pt and Adr administration. In addition, there was a significant difference (P0.05) increase in NO

7、and decline in MDA in IPC+I/R group (176.75069.057, 12.5403.100) of with I/R group (86.87532.874, 20.7300.700). However, there was no marked difference in the above parameters except MDA between IPC+I/R group and control group. CONCLUSIONS：The increase in electrocardiac stability through modifying c

8、ardiac ischemia by kidney IPC, in which NO could play an important role through increasing in scavenging of the oxygen free radical and also through vasodilation itself.MeSHIschemic; Kidney; Heart; ReperfusionMarber等1和陈魁等2的实验表明，缺血预处理(ischemic preconditioning, IPC)对缺血再灌流(ischemic reperfusion, I/R)心肌的

9、保护作用呈两个不连续的时相：早发的保护作用在23 h后消失，迟发的保护作用在24 h左右又可重现。进一步发现，IPC对肾和肝等器官亦具有早发和迟发的保护作用35。IPC的保护作用同其刺激体内热应激蛋白、超氧化物歧化酶(SOD)、丝裂素活化蛋白激酶、降钙素基因相关肽和腺苷等物质生成、释放增多有关15。这些内源性物质随血液循环至各组织器官，在体内是否形成一个保护系统?该系统在参与IPC减轻I/R器官损伤的同时，对其它器官是否亦具有保护作用?本文初步观察了肾IPC对心脏电稳定性的影响并探讨其机制。材料与方法(一)实验动物和分组：健康日本大耳白兔24只(本院标准动物饲养科提供)，雌雄不拘(2.00.3

10、) kg，随机分为对照组(n=6)、肾I/R组(n=9)和肾IPC+I/R组(n=9)。实验前禁食14 h，自由饮水。(二)实验处理和观察指标：在相对无菌条件下进行实验。用1%戊巴比妥钠30 mg.kg-1（iv）麻醉，腹正中切开57 cm。去右肾，游离左肾动脉。IPC+I/R组：用无创动脉夹夹闭左肾动脉5 min，去夹灌流10 min，反复3次后，再夹闭1 h，去夹行腹部缝合。10%葡萄糖10 mL.kg-1iv后，置笼内饲养。I/R组：手法模拟4次肾IPC过程后，夹闭左肾动脉1 h，余同IPC+I/R组。对照组：手法模拟4次IPC和1次I/R过程，余同IPC+I/R组。左肾再灌流24 h时

11、，用1%戊巴比妥钠25 mg.kg-1麻醉，记录导联心电(ECG)。ECG正常者，再用垂体后叶素(pituitrin, Pt)2 U.kg-1iv,在注Pt后10 min,给肾上腺素(adrenalin, Adr)0.03 mg.kg-1t检验测试。心律失常发生率用四格表精确检验法进行比较。结果(一)心电的变化：用Pt处理后，可见ST段抬高和室上性心律失常。ST段抬高：I/R组(0.2700.160)mV(n=8)，IPC+I/R组(0.0900.030)mV (n=7)，对照组(0.0800.020)mV(n=4)，I/R组分别同IPC+I/R组和对照组差异有显著(P0.05)。用Adr后，

12、一致出现心率增快，部分动物发生心律失常。I/R组心律失常发生率最高(88.89%)，IPC+I/R组最低(22.22%)，I/R组分别同IPC+I/R组和对照组(33.33%)差异有显著(表1)。心律失常的类型和该类型的发生数及持续时间，I/R组亦多于IPC+I/R组和对照组。I/R组：偶发结性早搏2例；结自身心律4例，时间34 min，偶发和频发室性早搏及阵发性室律过速各2例；室自身心律3例，时间12 min。IPC+I/R组：结性和室性早搏各1例。对照组：结自身心律2例，时间少于1 min；阵发性室律过速1例。表1三组心律失常的发生率Tab 1 Arrhythmogenic rate in

13、 three groupsGroupnGeneration No generationGenerative rate (%)I/R98188.89*IPC+I/R92722.22Control62433.33 *P0.05， vs IPC+I/R group or control(二)血中NO代谢物水平和心肌组织中MDA含量的变化：IPC+I/R组NO代谢物浓度最高，同I/R组差异显著；I/R组DMA含量最高，对照组最低，三组间差异均有显著(表2)。表2三组NO代谢物水平和MDA含量的变化GroupnNO-2NO-3(mol)MDA(nmol)I/R986.87532.874*20.7300.

14、700*IPC+I/R9176.75069.05712.5403.100Control6135.83324.6648.9903.030 *P0.05, vs control group or IPC+I/R group; P0.05, vs control group讨论Pt和Adr是常用的实验性致心肌缺血和诱发心律失常的药物。在心肌缺血的情况 下，Adr可进一步增加心脏活动的离散程度，易于发生心律失常。本文在肾缺血后再灌流24 h时，用Pt和Adr后，I/R组心肌缺血性改变的程度和心律失常发生率显著重于和高于IPC+I/R组，在IPC+I/R组和对照组间差异无显著性，提示IPC+I/R组动物心脏耐缺血的能力和电稳定性增强。NO由血管内皮生成，肾血管系统有很强的产生NO的能力，除自身强烈的舒血管作用外，还具有对抗缩血管物质如去甲肾上腺素和血管紧张素等对血管平滑肌的直接收缩作用；扩张入球小动脉，参与肾血流动力学和肾小球滤过率的调节；抑制血小板的粘着和聚集，减少在I/R期间微血栓的形成；增加氧自由基的清除，抑制白细胞在I/R组织内的粘附，减轻I/R对心、肾等器官的损伤6，7。在I/R肾损伤的动物体内，损伤和抗损伤机制同时启动。NO和MDA作为一对矛盾相互抗衡。在I/R组，由于MDA使NO灭活的作用占优势，NO浓度降低，对抗缩