伴有糖尿病的冠心病患者纤溶系统的变化及罗格列酮的干预研究

Change of fibrinolytic system in patients of coronary heart disease with type 2 diabetes and effect of intervention by rosiglitazone

目的通过观察伴有糖尿病(DM)的冠心病(CHD)患者纤溶系统的变化,并以罗格列酮进行干预,由此对罗格列酮防止支架术后再狭窄机制作初步探讨。方法试验对象共分为3组:伴有2型DM的CHD患者48例;不伴有2型DM的CHD患者36例;正常对照组:同期我院体检健康成人20例;3组对象均在入院后清晨抽血、分离血浆。检测一氧化氮(NO)、组织型纤溶酶原激活物(t-PA)和纤溶酶原激活物抑制剂(PAI-1)的含量;培养上清中NO采用硝酸还原酶法测定;t-PA和PAI-1采用酶联免疫法(ELISA)测定;另外将合并DM的CHD组48例患者分为两组,一组针对CHD和DM常规治疗,另一组在此基础上加用罗格列酮,4 mg/d,口服。治疗3个月后复查上述指标。结果伴有或不伴有DM的CHD患者NO的浓度分别为(40.83±5.34)μmol/L、(50.31±5.34)μmol/L均低于正常对照组(73.37±6.46)μmol/L(P均<0.01);t-PA的浓度分别为(18.53±7.05)μg/L、(26.72±8.20)μg/L均低于正常对照组(40.17±8.30)μg/L(P均<0.01);PAI-1的浓度分别为(86.04±8.88)μg/L(、78.52±7.34)μg/L均高于正常对照组(48.86±5.41)μg/L(P<0.01);伴有DM的CHD患者NO和t-PA的浓度均低于不伴有DM的CHD患者组(P<0.05),PAI-1的浓度高于不伴有DM的CHD患者组(P<0.05)。伴有DM的CHD患者常规治疗和常规+罗格列酮治疗后NO,t-PA显著高于治疗前:NO治疗前后的变化值分别为(20.97±3.49)μmol/L、(30.32±3.36)μmol/L(P均<0.01);t-PA治疗前后的变化值分别为(11.97±2.07)μg/L、(21.32±2.21)μg/L(P均<0.01);伴有DM的CHD患者常规治疗和常规+罗格列酮治疗后PAI-1的浓度显著低于治疗前,PAI-1治疗前后的变化值分别为(-23.98±5.12)μg/L、(-34.02±5.64)μg/L(P<0.01);和常规组比较,常规+罗格列酮治疗组改善的幅度要高于常规组(P<0.01)。结论伴或不伴DM的CHD患者冠心病患者体内存在不同程度纤溶活性的降低,这种高凝状态会促进血栓形成和再狭窄的发生。对于冠心病患者,在常规冠心病治疗基础上,加用罗格列酮能促进纤溶系统的激活,防止血栓的形成,有效防止支架术后再狭窄,特别是对于伴有糖尿病的CHD患者。

Objective To determine change of fibrinolytic system in the patients with coronary heart disease （CHD） and type 2 diabetes mellitus（DM） and to find the effect of intervention by roslglitazone for the underlying mechanisms of rosiglitazone in prevention of restenosis after percutaneous coronary intervention（PCI）. Methods The blood samples were taken from the patients of three groups.（1）48 CHD patients with type 2 DM, （2）36 patients only with CHD and （3） 20 healthy subjects. Plasma nitric oxide（NO） was assessed with revert enzymetic means of nitric acid; tissue plasminogen activator（t-PA） and plasminogen activator inhibitor（PAI-1） were measured by enzyme linked immunosorbent assay（ELISA）. The CHD patients of coronary heart disease with type 2 DM were subdivided into two groups. One group was treated by conventional therapy, the other group was treated by conventional therapy plus rosiglitazone（4 mg/d）. NO, t-PA and PAI-1 were measured after treatment of three months. Results The concentrations of NO and t-PA in the CHD patients were lower than those of normal control（ P 〈0.01）,but PAI-1 was higher. NO and t-PA in patients of type 2 DM with CHD were lower than those of the patients with non- type 2 DM（ P 〈0.01）,PAI-1 was higher accordingly（ P〈0.05）. The concentrations of NO and t-PA in the CHD patients with type 2 DM were higher after treated by conventional therapy or conventional therapy plus rosiglitazone（ P〈0.01） ,and PAI-1 was lower, too. The extent of improvement in the group of conventional therapy plus rosiglitazone was better than that of the group of conventional therapy（ P〈0.01）. Conclusion The activity of fibrinolytic system in some extent is degraded in the patients with CHD. The hypercoagulable state will promote thrombogenesis and restenosis after PCI. Rosiglitazone associated with conventional therapy can promote the activation of fibrinolytic system and prevent thrombogenesis, which may prevent restenosis after PCI in patients with CHD, especially in the CHD patients with type 2 DM.