赤芍总甙对犬急性缺血心肌的保护作用

Protective effects of total saponins of paeonia on acute ischemic myocardium in canines

目的:从电生理学、酶学、定量组织学方面探讨赤芍总甙对犬急性心肌缺血的保护作用。方法:①实验于2004-06/2004-10在吉林大学基础医学院机能科学实验中心实验室完成。选用健康成年杂种犬30只。结扎麻醉开胸制备犬左冠状动脉前降支缺血急性心肌缺血模型,将造模后大鼠30只随机分为5组:空白对照组,复方丹参组,赤芍总甙1.5,3.0,6.0mg/kg组,每组6只。②空白对照组静注等容量的生理盐水,复方丹参组静注复方丹参注射液2.0mg/kg,赤芍总甙1.5,3.0,6.0mg/kg组静注赤芍总甙1.5,3.0,6.0mg/kg。③记录结扎即刻、给药后10,30,45,60,90,120min心外膜电图,以ST段升高总mV数表示缺血程度,以ST段升高≥2mV的导联数为缺血范围。④计算心肌梗死面积(梗死心肌质量/左心室质量×100%)。⑤根据试剂盒说明操作测定血清磷酸肌酸激酶、乳酸脱氢酶、谷草转氨酶、超氧化物歧化酶、谷胱甘肽过氧化物活性及游离脂肪酸、过氧化脂质含量。⑥计量资料差异性比较采用t检验。结果:犬30只均进入结果分析。①赤芍总甙对急性心肌梗死犬缺血程度的影响:赤芍总甙1.5mg/kg组和复方丹参组给药后30～120min缺血程度明显低于对照组(t=2.273～3.963,P<0.05～0.01)。赤芍总甙3.0和6.0mg/kg组给药后10～120min缺血程度均明显低于对照组(t=2.684～5.233,P<0.05～0.01)。②赤芍总甙对急性心肌梗死犬心肌缺血范围的影响:赤芍总甙1.5mg/kg组和复方丹参组在给药后30～120min心肌缺血范围明显小于对照组(t=2.527～3.178,P<0.05)。赤芍总甙3.0和6.0mg/kg组给药后10～120min心肌缺血范围明显小于对照组(t=2.564～5.195,P<0.05～0.01)。③赤芍总甙对犬梗死面积和心肌酶学指标的影响:复方丹参注射液组,赤芍总甙1.5,3.0,6.0mg/kg组心肌梗死面积、血清磷酸肌酸激酶、乳酸脱氢酶、谷草转氨酶活性均明显低于对照组(P<0.05～0.01)。④赤芍总甙对急性心肌梗死犬血清游离脂肪酸和抗氧化酶活性和影响:赤芍总甙3.0,6.0mg/kg组和复方丹参注组血清游离脂肪酸及过氧化脂质含量明显低于对照组(t=2.919～4.640,P<0.05～0.01),超氧化物歧化酶及谷胱甘肽过氧化物酶活性明显高于对照组(t=2.331～3.544,P<0.05～0.01)。赤芍总甙1.5mg/kg组血清游离脂肪酸含量明显低于对照组(P<0.05)。结论:①赤芍总甙可减少心肌缺血程度,降低缺血范围和心肌酶学指标的活性,说明赤芍总甙具有抗心肌缺血作用。②赤芍总甙能明显抑制血清游离脂肪酸含量升高,降低过氧化脂质,通过增加血清超氧化物歧化酶、谷胱甘肽过氧化物活性。表明赤芍总甙是通过改善心外膜电图,提高心肌供血,对抗脂质过氧化反应,稳定细胞膜,保护内源性抗氧化酶活性发挥抗心肌缺血作用。

AIM： To investigate the protective effects and the mechanism of total saponins of paeonia on acute myocardial ischemia in canines from the aspects of electrophysiology, enzymology and quantitative histology. METHODS： ① The experiments were finished in the Experimental Center of Functional Sciences, College of Basic Medical Science, Jilin University between June and October 2004. Thirty healthy adult mongrel canines were made into models of acute myocardial ischemia by ligating the left anterior descending of coronary artery, and then the models were randomly divided into five groups with 6 canines in each group： normal control group, compound danshen group, total saponins of paeonia 1.5, 3.0 and 6.0 mg/kg groups. ②The canines were treated with venous injections of saline of the same volume in the blank control group, compound danshen parenteral solution （2.0 mg/kg） in the compound danshen group, total saponins of paeonia （1.5, 3.0 and 6.0 mg/kg groups） in the total saponins of paeonia 1.5, 3.0 and 6.0 mg/kg groups respectively. ③The epicardial electrocardigram was recorded immediately after ligation and at 10, 30, 45, 60, 90 and 120 minutes respectively, the ischemic severity was expressed with the ST-segment total increased mV number, and the ischemic range was expressed with the. increased ST-segment lead number≥ 2 mV. ④The myocardial infarcted area was calculated （infarcted myocardial area/left ventricular mass×100%）. ⑤Fhe activities of serum phosphocreatine kinase, lactate dehydrogenase, glutamic oxalacetic transaminase, superoxide dismutase and glutathione peroxidase and the contents of free fatty acid and lipid peroxide were detected according to the instruction of the kit. ⑥The difference of the measurement data was compared with the t test. RESULTS： All the 30 canines were involved in the analysis of results. ① Influence of total saponins of paeonia on the ischemic severity of canines with acute myocardial ischemia： The ischemic severities at 30- 120 minutes after treatment in the total saponins of paeonia 1.5 mg/kg group and compound danshen group were obviously lower than that in the control group （t=2.273-3.963,P 〈 0.05-0.01）; The ischemic severities at 10-120 minutes after treatment in the total saponins of paeonia 3.0 and 6.0 mg/kg groups were obviously lower than that in the control group （t =2.684-5.233, P 〈 0.05-0.01）. ②Influence of total saponins of paeonia on the ischemic range of canines with acute myocardial ischemia： The ischemic ranges at 30-120 minutes after treatment in the total saponins of paeonia 1.5 mg/kg group and compound danshen group were obviously smaller than that in the control group （t=2.527-3.178, P 〈 0.05）; The ischemie ranges at 10-120 minutes after treatment in the total saponins of paeonia 3.0 and 6.0 mg/kg groups were obviously smaller than that in the control group （t=2.564-5.195, P 〈 0.05-0.01）. ③The effects of total saponins of paeonia on the infarcted area and myocardial enzymological indexes of canines with acute myocardial ischemia： The myocardial infarcted area and serum activities of phosphocreatine kinase, lactate dehydrogenase and glutamic oxalacetic transaminase were obviously lower in the compound danshen group and total saponins of paeonia 1.5, 3.0and 6.0 mg/kg groups than in the control group （P 〈 0.05-0.01）. ④The effects of total saponins of paeonia on the serum free fatty acid and antioxidase activity of canines with acute myocardial ischemia： The serum contents of free fatty acid and lipid peroxide in the total saponins of paeonia 1.5, 3.0 and 6.0 mg/kg groups and compound danshen group were obviously lower than those in the control group （t=2.919-4.640, P 〈 0.05-0.01）, and the activities of superoxide dismutase and glutathione peroxidase were markedly lower than those in the control group （t =2.331-3.544, P 〈 0.05-0.01）. The serum content of free fatty acid was markedly lower in the total saponins of paeonia 1.5 mg/kg group than in the control group （P 〈 0.05）. CONCLUSION： ①Total saponins of paeonia can reduce the myocardial ischemic severity, decrease the ischemic range and activities of myocardial enzymological indexes, it is indicated that total saponins of paeonia has the effect of anti-myocardial ischemia. ② Total saponins of paeonia can obviously inhibit the increase of serum level of free fatty acid, decrease lipid peroxide by increasing the serum activities of superoxide dismutase and glutathione peroxidase, indicating that total saponins of paeoniathe plays a role against myocardial ischemia by improving epicardial electrocardigram, increase myocardial blood supply, antagonizing lipid peroxidation, stabilizing the cell membrane and protecting the activity of the endogenic antioxidase.