参附注射液预先给药对糖尿病兔心肌缺血再灌注时冠状动脉的影响

Protective effects of shenfu injectio pretreatment on coronary artery against ischemia-reperfusion injury in rabbits with diabetes mellitus

目的探讨不同剂量参附注射液（SFI）预先给药对糖尿病兔心肌缺血再灌注时冠状动脉的影响。方法糖尿病模型制备成功的家兔40只,喂养8周后,随机分为5组（n=8）,结扎-开放冠状动脉左前降支（LAD）建立心肌缺血再灌注模型。分别于结扎冠状动脉前30min静脉注射生理盐水10ml/kg（NS组）、SF15ml/kg（SF1组）、SFI 10ml/kg（SF2组）、SFI 15ml/kg（SF3组）,假手术组（S组）只穿线环绕LAD而不结扎。于结扎LAD前即刻（T1）、开放LAD前即刻（T2）、开放后120min（T3）时颈总动脉取血,测定血清一氧化氮（NO）、内皮素-1（ET-1）和血栓素B2（TXB2）的浓度,计算冠脉灌注压（CPP）;取LAD,测定其在硝普纳（SNP）和去甲肾上腺素（NE）作用下的张力。结果T2,3时SF2组CPP恢复率高于NS组和SF1组,T3时SF3组CPP恢复率低于NS组（P〈0.05）;与T1时相比,T2,3时NS组血清NO浓度降低,NS组、SF1组、SF2组和SF3组TXB2浓度均升高,T2时NS组、SF1组和SF3组血清ET-1浓度升高（P〈0.05）;与NS组相比,T2,3时SF2组血清NO浓度升高,ET-1、TXB2浓度降低（P〈0.05）;SF3组T3时血清NO浓度高于NS组（P〈0.05）;与S组相比,在NE作用下其余各组冠状动脉收缩张力均降低（P〈0.05）;SF1组和SF2组冠状动脉收缩张力高于NS组,SF2组收缩张力高于SF1组（P〈0.05）;在SNP作用下,SF2组冠状动脉舒张张力低于S组,其余各组均高于S组（P〈0.05）。结论SFI预先给药对糖尿病兔心肌缺血再灌注时冠状动脉具有一定的保护作用,SFI 10 ml/kg时效果最好。

Objective To investigate the protective effects of different doses of shenfu injectio pretreament on the coronary artery against ischemia-reperfusion （I/R） injury in rabbits with diabetes mellitus. Methods Forty adult male diabetic rabbits weighing 2-3 kg were used in this study. Diabetes mellitus was induced with intravenous alloxan 120 mg/kg. Eight weeks later the animals were randomly divided into 5 groups （ n = 8 each） ： group sham operation （C）; group Ⅱ myocardial I/R; group Ⅲ, Ⅳ and Ⅴ received shenfu injectio 5, 10, 15 ml/kg respectively at 30 min before myocardial ischemia （SF1 , SF2, SF3 ）. A catheter was inserted into left ventricle via left common carotid artery for determination of left ventricular end-diastolic pressure （ LVEDP）. Right femoral artery was connulated for BP monitoring. Myocardial I/R was produced by temporary ligation of anterior descending branch of left coronary artery （LAD） for 60 min followed by 120 min reperfusion. Myocardial ischemia was confirmed by S-T segment elevation and change in color of myocardium. Blood samples were obtained immediately before ligation of LAD （T1）, immediately before LAD ligation was untied （T2） and 120 min after LAD was untied （T3 ） for determination of serum NO, ET-1 and TXB2 concentrations and coronary perfusion pressure （CPP） （ CPP = LVEDP- DBP）. The animals were then sacrificed and LAD was isolated and its vasomotor reaction to noradrenaline （NE） and sodium nitroprusside （SNP） were examined. Results （ 1 ） The recovery rate of CPP was significantly better at T2 and T3 in group SF2 （Ⅳ） than in group Ⅱ , Ⅲ and Ⅴ . （2） Serum NO concentration was significantly decreased while serum TXB2 and ET-1 concentrations were significantly increased at T2 and T3 compared to the baseline values at T1 in group I/R （group Ⅱ ）. （3） Serum NO concentration was significantly higher while serum ET-1 and TXB2 concentrations were significantly lower at T2 and T3 in group SF2 than in group I/R. （4） The vascular tension was significantly higher in the presence of NE and lower in the presence of SNP in group SF2 than in group I/R, SF2 and SF3. Conclusion Pretreatment with shenfu injectio can protect coronary artery against I/R injury in diabetic rabbit. Shenfu injectio 10 ml/kg provides best protective effect.