摘要
目的 研究硝酸甘油 (nitroglycerin ,NG)和丁丙诺啡(buprenorphine,BU)两药单用及合用抗心肌缺血的药理性预适应的早期保护作用。方法 ♂Wistar大鼠分为 5组 ,行 30min冠脉结扎缺血 / 2h再灌。各组手术之前行不同处理 ,Sham组静注等容积NS ,早期预适应 (EIP)组行 3个循环5min缺血 / 5min再灌预处理 ,BU组静注盐酸丁丙诺啡 1 0mg·kg-1,NG组静注NG 0 3mg·kg-1,B +N组分别给上述剂量BU和NG。各组均于给药前、后及缺血和再灌期连续监测心率、血压、ST 段和心律失常情况 ;测定缺血 30min和再灌 2h血浆LDH、CK ;再灌 2h后行心肌HE染色与TTC染色定性和定量测定心肌坏死情况。结果 与Sham组比较 ,BU组明显推迟缺血期心律失常出现时间 ,缩短室早持续时间 (P <0 0 1) ,降低二联律和室速发生率 ;降低缺血期血LDH(P <0 0 5 )水平 ,缩小心肌坏死面积 (P <0 0 1) ,但未降低血CK水平和缺血期ST 段抬高。与Sham组比较 ,NG组明显降低缺血和再灌期ST段 (P <0 0 1)、降低缺血期血LDH(P <0 0 1)和CK(P <0 0 5 )水平 ,缩小心肌坏死面积 (P <0 0 1) ,减轻HE染色心肌坏死程度 ,缩短心律失常持续时间。药物合用后与Sham组比较 ,不仅明显降低缺血和再灌期ST段、血LDH和CK水平 ,缩小心肌坏死面积 (P <0 0 1) 。
AIM To study the early cardioprotective effects of pharmacological preconditioning of nitroglycerin (NG) and buprenorphine (BU) used alone and in combination on myocardial ischemia in rats. METHODS Male Wistar rats were randomized to 5 groups. The ischemia and reperfusion injury was induced by ligation of the left arterior descending coronary arrery for 30 min and followed reperfusion for 2 h. The rats were subjected to different treatments before I/R. Normal saline (NS) was infused intravenously with the same volume of NG and BU in Sham group. Ischemia/preconditioning (IP) was performed by three cycles of 5 min I/R in EIP group. BU (1 0 mg·kg -1 ) and NG (0 3 mg·kg -1 ) was administered intravenously alone in BU and NG group or given together in B+N group to mimic the effects of IP, respectively. Heart rate, blood pressure, ST segment and arrhythmias were recorded continuously throughout the whole test. Plasma LDH and CK were measured on 30 min after ischemia and 2 h after reperfusion, HE and TTC staining were performed to determine myocardial necrosis at the end of test. RESULTS Compared with Sham group the onset of arrhythmias was delayed and the duration of ventricular premature contraction (VPC) was shortened remarkably ( P <0 01). The incidence of bigeminy and ventricular tachycardia (VT) decreased as well. The plasma LDH and infarct size reduced, respectively ( P <0 01). Compared with Sham group, the elevation of ST segment corresponding to ischemic injury decreased and the duration of ventricular arrhythmias (VA) shortened in NG group significantly ( P <0 01). Plasma LDH ( P <0 01), CK ( P <0 05) and infarct size ( P <0 01) were also lowered than Sham group. Morphology observation by HE staining showed that the I/R injury on myocytes was attenuated by NG. ST segment elevation, plasma concentration of LDH and CK, the onset and the duration of VA, the infarct size of heart were all better than those of NG or BU alone in B+N group ( P <0 05). CONCLUSION The mimic early cardiaprotective effects of IP by NG and BU were confirmed on I/R model. Furthermore, combined used NG and BU used in combination were more effectively than used them alone.
出处
《中国药理学通报》
CAS
CSCD
北大核心
2003年第10期1119-1124,共6页
Chinese Pharmacological Bulletin
基金
天津市自然科学基金项目 No 993 60 8111
关键词
硝酸甘油
丁丙诺啡
药理性预适应
早期心脏保护
nitroglycerin
buprenorphine
pharmacological preconditioning
early cardioprotection
