四氢生物蝶呤的心肌保护作用及对细胞间黏附分子-1表达的影响

Effect of tetrahydrobiopterin on myocardial protection and intercellular adhesion molecular 1 expression

目的 探讨四氢生物蝶呤 (BH4)对缺血再灌注心肌的保护作用及对细胞间黏附分子 1(ICAM 1)表达的影响。方法 建立Langendorff离体心脏灌注模型 ,60只Wistar大鼠随机分为实验组 (BH4停搏液 )和对照组 (St .ThomasⅡ液 ) ,每组 3 0只。分别于相应的时间点测定两组心脏功能恢复 ,心肌组织丙二醛 (MDA)、超氧化物歧化酶 (SOD)、一氧化氮 (NO )和一氧化氮合酶(NOS)的含量变化及ICAM 1的表达。结果 BH4能显著提高心脏功能恢复 ,增强缺血再灌注后NOS的活性 ,增加NO的产量 ,抑制ICAM 1的表达并降低MDA的产生 (P均 <0 .0 5 )。结论 BH4具有显著的抗心肌缺血再灌注损伤 (MIRI)的作用。

Objective To study the effects of tetrahydrobiopterin (BH4) on myocardial protection and intercellular adhesion molecular-1 (ICAM-1) expression.Methods The isolated,crystalloid-perfused rat heart model was perfused retrogradely in the isolated Langendorff model at a constant pressure of 70 mm Hg with 37 ℃ oxygenated KH buffer.Sixty Wistar rats were divided randomly into two groups:control group and experimental group (n=30 in each group).After 15 min equilibration,the hearts of both groups were perfused retrogradely with 4 ℃ different cardioplegia for 2 min.The hearts in control group received St.ThomasⅡ solution,and the hearts in experimental group were subjected to BH4 in the cardioplegic solution (20 μmol/L).The hearts in control group and experimental group received global ischemia for 30 min and reperfused with KH solution at 37 ℃ for 120 min.The samples were collected at equilibration,postischemia and 30,60,120 min after reperfusion respectively in both groups.The left ventricular end systolic pressure (LVESP),left ventricular end diastolic pressure (LVEDP) and it's first derivative (±dp/dtmax) were recorded in order to evaluate the left ventricular function at the equilibration and 120 min after reperfusion.The myocardial contents of malonaldehyde (MDA),superoxide dismutase (SOD),nitric oxide (NO) and nitricoxide synthase (NOS) were measured at the corresponding points.The expression of myocardial ICAM-1 was detected by using ABC-ELISA at the equilibration and 30,60,120 min after reperfusion.Results Compared with the control group,the hearts in the experimental group had a higher recovery rate of cardiac function (P<0.05),lower myocardial MDA content and ICAM-1 expression (P<0.05).BH4 cardioplegia could increase myocardial contents of SOD,NO and NOS much more than St.ThomasⅡcardioplegia (P<0.05).Conclusion BH4 cardioplegia may have better myocardial protective effects than St.ThomasⅡcardioplegia by increasing NO,decreasing ICAM-1 expression and reducing oxygen-derived free radicals.