目的 探讨聚乙二醇（PEG）化葛根素对大鼠心肌缺血再灌注损伤（MIRI）的保护作用。方法 将SD大鼠随机分为6组（每组10只）： 假手术组，MIRI模型组，葛根素注射剂（20 mg/kg）对照组，PEG化葛根素低、中、高剂量（244、488、976 mg/kg）组。阻断大鼠升主动脉造成心肌缺血30 min，再灌注120 min，造成大鼠MIRI模型，在结扎后5 min各给药组尾iv给药。心电图监测心律失常情况，再灌注结束后腹主动脉采血，测定血清肌酸激酶（CK）、乳酸脱氢酶（LDH）、天冬氨酸转氨酶（AST）和丙二醛（MDA）水平，并测量心肌梗死面积。结果 葛根素注射剂和PEG化葛根素均具有抗心律失常，降低血清中CK、LDH、AST和MDA水平的作用，减少心肌梗死面积；其中PEG化葛根素中、高剂量组的药效明显强于葛根素注射剂组。结论 PEG化葛根素对大鼠MIRI引起的损伤具有保护作用。

Objective To investigate the protective effect of PEGylated puerarin on the myocardial ischemia-reperfusion injury (MIRI) in rats. Methods Sixty healthy SD rats were randomly divided into six groups: Sham, MIRI model, puerarin injection (20 mg/kg, positive control), low-, mid-, and high-dose PEGylated puerarin (244, 488, and 976 mg/kg) groups. MIRI rat model was carried out by ligation of left anterior descending coronary artery for 30 min followed by reperfusion for 120 min. Different doses of PEGylated puerarin and puerarin injection were given 5 min after the ligation. Concomitant arrhythmias was surveyed by electrocardiogram, and the blood was collected at the end of reperfusion for detecting the changes of creatine kinase (CK), lactic dehydrogenase (LDH), aspartate aminotransferase (AST), and malondialdehyde (MDA). The myocardial infarct size was also estimated. Results Both puerarin injection and PEGylated puerarin exhibited the antiarrhythmic activity, decreased the contents of CK, LDH, AST, and MDA, and reduced the myocardial infarct size. The efficacy of mid- and high-dose PEGylated puerarin groups was better than that of puerarin injection group. Conclusion PEGylated puerarin exerts the protective effects on MIRI in rats.

科技部重大新药创制专项（2009ZX09502-007）