三七茎叶皂苷对大鼠离体心脏缺血/再灌注损伤的保护作用

Protective effects of PnGL on ischemia/reperfusion injury in isolated rat hearts

目的研究三七茎叶皂苷对大鼠离体心脏缺血/再灌注(I/R)损伤的作用及其作用机制。方法 SD大鼠36只,随机分为6组(n=6),分别是空白对照组、模型组、阳性给药组(地奥心血康70 mg.kg-1)、三七茎叶皂苷低、中、高剂量组(20、40、80 mg.kg-1)。阳性给药组和三七茎叶皂苷给药组大鼠每日灌胃给药1次,连续给药7 d,空白对照组和模型组同时给予同体积生理盐水。末次给药60 min后,分离心脏置于Langendorff离体灌流装置上,平衡15 min后,全心停灌25 min,再灌注60 min,造成心肌缺血/再灌注损伤模型。于大鼠左心房插入水囊导管,记录三七茎叶皂苷对血流动力学指标的影响,测定再灌注60 min后灌流液中乳酸脱氢酶(LDH),肌酸激酶(CK)的活性及心肌组织中超氧化物歧化酶(SOD)、谷胱甘肽过氧化物酶(GSH-Px)、LDH、CK活性及丙二醛(MDA)的含量。HE染色观察组织形态学改变。结果三七茎叶皂苷不同剂量组(20、40、80 mg.L-1),可明显改善缺血/再灌注所致大鼠的心功能损伤,减少灌流液中LDH、CK释放和组织中MDA的产生,增加SOD、GSH-Px的活性。HE染色结果显示,阳性给药组与三七茎叶皂苷高、中、低剂量组均不同程度的减轻了I/R造成的心肌损伤。结论三七茎叶皂苷对心肌缺血/再灌注损伤具有保护作用,其机制可能与改善心肌舒缩功能,清除氧自由基,减少脂质过氧化反应有关。

Aim To investigate the protective effect of Panax notoginsegnoside of leaves（PnGL） on myocardial ischemia/reperfusion（I/R） injury in isolated rat hearts and its underlying mechanisms.Methods Thirty-six SD rats were divided into 6 groups randomly（n=6）：control group;model group（I/R group）;positive drug group（DiAo group 70 mg·kg-1）;PnGL low,middle,high dose groups（20,40,80 mg·kg-1）.Positive drug and PnGL were administered once a day to rats for 7 consecutive days.60 min after last administration,the hearts were isolated and perfused with krebs-Henseleit buffer solution on Langendorff apparatus.Hearts were in equilibrium for 15min,then after 25min of global ischemia,isolated hearts were reperfused for 60min.Myocardial hemodynamic parameters were monitored and recorded,and biochemical parameters,such as lactate dehydrogenase（LDH）,creatine kinase（CK） in perfusate and myocardial tissue,antioxidative parameters such as superoxide dismutase（SOD）,GSH-Px,MDA in left ventricles were measured as well.Histopathological examination of left ventricles was performed.Results It was found that the levels of CK and LDH in I/R-induced rats were significantly increased.The rats treated with I/R showed the declines in left ventricular systolic pressure,positive andnegative maximal values of the first derivative of left ventricular pressure,and an elevation of left ventricular end diastolic pressure.Model group enhanced the content of malondialdehyde and decreased the activities of SOD,GSH-Px in left ventricles.Administration of PnGL significantly ameliorated myocardial injury and heart function impairment induced by global I/R.The cardioprotective effect of PnGL was further confirmed by histopathological examination.PnGL also alleviated the increase of MDA content and decrease of SOD and GSH-Px activities in left ventricles.Conclution The results indicates that PnGL possesses the effect against global I/R-induced myocardial injury and heart function impairment,and that the mechanism of pharmacological action is related to the antioxidant activity of PnGL.