两种不同钙离子拮抗剂SK&F96365和LOE908对心肌缺血再灌注损伤的保护效果比较

Comparation of protective effects between SK&F96365 and LOE908 on ischemia / reperfusion injury in rats

目的运用大鼠活体心肌缺血再灌注（ischemia／reperfusion，1／R）损伤模型，比较两种不同钙离子拮抗剂SK＆F96365和LOE908的心肌保护效果。方法健康雄性SD大鼠24只．250～300g，按随机数字表法随机分为4组（n=6）：Sham组、I／R组、SK＆F96365组和LOE908组。开胸后所有大鼠心脏适应10min．其中Sham组用5—0丝线穿过左冠状动脉前降支不缝扎90min。I／R组用5-0丝线缝扎左冠状动脉前降支30min后松开丝线恢复灌注60min。SK＆F96365组和LOE908组在I／R组基础上，分别在恢复灌注即刻静脉注射0．06mg／kgSK＆F96365和0．1mg／kgLOE908。测定各组大鼠颈动脉血浆内皮素-1（endothelin-1，ET-1）浓度和检测乳酸脱氢酶（lactate dehydrogenase，LDH）和肌酸激酶同功酶（creatine kinase isoenzyme，CK-MB）浓度及心肌梗死面积。结果与Sham组相比，I／R组、SK＆F96365组和LOE908组中ET-1浓度均有所增高，差异有统计学意义（P〈0．05）。SK＆F96365组与LOE908组相对I／R组而言，LDH与CK—MB浓度降低，梗死面积减少，差异有统计学意义（P〈0．05）；但SK＆F96365组血浆LDH、CK—MB浓度及心肌梗死面积与LOE908组比较，差异无统计学意义（P〉0．05）。结论SK＆F96365和LOE908两种不同的钙离子拮抗剂均可对大鼠活体心脏I／R损伤起保护作用，但两者之间的保护作用并没有差别。

Objectives To compare the cardioprotective effects of two different calcium antagonists SK＆F96365 and LOE908 on rats with ischemia/reperfusion （I/R） injury. Methods Twenty-four healthy male SD rats （250-300 g） were randomly subjeeted to 4 groups （n=6）： （1） Sham group [A 5-0 prolene suture was passed around the left anterior descending coronary artery （LAD） without I/R for 90 mini ; （2）I/R group [A 5-0 prolene suture was passed around the left anterior descending coronary artery （LAD）. Ischemia was induced by ligation of the LAD for 30 min and reperfusion by loosing the prolene suture for 60 min ] ; （3）SK＆F96365 group [ Based on I/R group, SK＆F96365 （0.06 mg/kg） was injected intravenously after 30 mins＇ ischemia] ; （4）LOE908 group [Based on I/R group, LOE908 （0.1 mg/kg） was injected intravenously after 30 mins＇ ischemia]. Concentration of plasma endothelin-1 （ET-1） was detected. Lactate dehydrogenase （LDH） and creatine kinase isoenzyme （CK-MB） in carotid artery were examined to assess heart I/R injury. Triphenyltetrazolium chloride （TrC） staining was used to assess viability of myocardial tissue and identification of myocardial infarction. Results Compared with sham group, concentrations of plasma ET-1 in I/R group, SK＆F96365 group and LOE908 group increased to some extent （P〈0.05）. Compared with I/R group,concentrations of LDH and CK-MB in SK＆F96365 group and LOE908 group decreased significantly and infarct sizes were smaller （P〈O.05）. However, there was no difference between SK＆F96365 group and LOE908 group in concentrations of LDH and CK-MB and myocardial infarct size （P〉0.05）. Conclusions The two different calcium antagonists SK＆F96365 and LOE908 both provide similar protective effects against I/R injury.