广枣叶总黄酮对心肌缺血再灌注损伤模型大鼠的保护作用及其作用机制

Myocardial protective function and mechanism of total flavonoids from Jujube leaves after myocardial ischemia-reperfusion injury in rats

目的分析广枣叶总黄酮灌胃对心肌缺血再灌注损伤大鼠心肌功能的保护作用,并探讨可能存在的作用机制。方法将60只健康SPF级大鼠作为研究对象,采用随机数字表法将大鼠分为5组,分别为伪手术组、阳性对照组、模型组、小剂量给药组、大剂量给药组。阳性对照组给予0.02 g·kg^-1维拉帕米灌胃,小剂量组给予0.2 g·kg^-1广枣叶总黄酮混悬液灌胃,大剂量组给予0.4 g·kg^-1广枣叶总黄酮混悬液灌胃,伪手术组与模型组均给予同等容量生理盐水灌胃。用药7 d后,除伪手术组大鼠,其余4组大鼠均制备心肌缺血再灌注损伤模型。手术完毕将5组大鼠处死,分别进行血清生化、心肌生化、心律失常、心肌梗死和组织形态学等指标检测与比较,重点探讨广枣叶总黄酮对大鼠再灌注损伤的保护效果与作用机制。结果与伪手术组相比,模型组大鼠的SOD活性降低,MDA、CK、LDH含量明显升高,室性心动过速、室颤发生次数及持续时间升高,出现严重心肌梗死,各指标比较差异均有统计学意义(P<0.05)。阳性对照组、小剂量给药组与大剂量给药组在用药7 d后,上述各指标均得到不同程度改善,相较模型组差异显著(P<0.05)。伪手术组大鼠心肌胶原纤维整齐排列,形态正常,无红细胞及炎细胞浸润改变,而模型组心肌原纤维增多,排列紊乱,细胞核固缩,其余3组心肌组织病理改变得到修复,其中大剂量给药组心肌组织形态改善更显著。结论广枣叶总黄酮对心肌缺血再灌注损伤大鼠具有保护作用,其可能通过抑制丙二醛生成,减少氧自由基,降低心肌酶漏出等机制,控制炎症反应、改善心肌梗死的不良后果。

Objective To analyze the protective effect of total flavonoids from jujube leaves on myocardial function in rats after myocardial ischemia-reperfusion injury,and to explore the possible mechanism of action.Methods Sixty healthy SPF rats were used as the study subjects.The rats were divided into five groups by random number table method,which were sham operation group,positive control group,model group,low dose group and high dose group.The positive control group was given 0.02 g·kg^-1 verapamil orally;the low dose group was given 0.2 g·kg^-1 Guangzao leaf total flavonoid suspension;and the high dose group was given 0.4 g·kg^-1 Guangzao leaf total flavonoid suspension by intragastric administration;the sham operation group and the model group were given the same volume of normal saline.After 7 days of treatment,except for the rats in the sham operation group,the other four groups of rats were prepared for myocardial ischemia-reperfusion injury model.Five groups of rats were sacrificed after operation,and serum biochemistry,myocardial biochemistry,arrhythmia,myocardial infarction and other indicators were detected and compared,and the protective effect and mechanism of total flavonoids from jujube leaves on reperfusion injury in rats were studied.Results Compared with the sham operation group,the SOD activity of the model group decreased,the MDA,CK,LDH levels increased significantly,the ventricular tachycardia,the number and duration of ventricular fibrillation increased,and severe myocardial infarction occurred,and the differences between the indicators were statistically significant(P<0.05).The positive control group,the low-dose group and the high-dose group were all improved in different degrees after 7 days of treatment,which was significantly different from the model group(P<0.05).In the sham operation group,the myocardial collagen fibers were neatly arranged,the morphology was normal,and no red blood cells and inflammatory cells infiltrated,while the model group had increased myocardial fibrils,disordered arrangement,nucleus pyknosis,and the remaining three groups of myocardial tissue pathological changes were repaired,of which large doses were obtained,among them the myocardial tissue morphology of the high-dose group was improved more significantly.Conclusion The total flavonoids from jujube leaves have protective effects on myocardial ischemia-reperfusion injury in rats,which may be through inhibit malondialdehyde production,reduce oxygen free radicals,reduce myocardial enzymes and other mechanisms,to control the inflammatory response and improve myocardial infarction.