香青兰总黄酮对大鼠心肌缺血再灌注损伤诱导的自噬作用的研究

Effect of Dracocephalum Total Flavonoids on Myocardial Ischemia/Reperfusion-Induced Autophagy in Rats

目的研究香青兰总黄酮对大鼠心肌缺血再灌注损伤诱导的自噬作用。方法采用结扎左冠状动脉前降支的方法,缺血30 min,再灌120 min,构建大鼠在体心肌缺血再灌注损伤模型。分别给予香青兰总黄酮(30 mg·kg^(-1)·d^(-1))灌胃、自噬激活剂(1 mg·kg^(-1)·d^(-1))与抑制剂(25 mg·kg^(-1)·d^(-1))腹腔注射预处理。观察梗死面积、血浆乳酸脱氢酶(LDH)、肌酸激酶同工酶(CK-MB)和组织凋亡蛋白caspase-3的活性及从蛋白与RNA水平检测自噬相关蛋白LC3、Beclin-1的表达。结果自噬抑制剂组能减轻缺血再灌注导致的心肌损害,减少梗死面积及心肌酶溢漏,降低凋亡蛋白caspase-3的活性;香青兰总黄酮预处理显著减少自噬相关蛋白LC3、Beclin-1的表达。结论香青兰总黄酮对心肌缺血再灌注损伤心肌中的自噬有明显抑制作用,抑制自噬可能是香青兰总黄酮抗心肌缺血作用的主要机制。

OBJECTIVE To explore the effects of Dracocephalum total flavonoids （TFDM） on myocardial ischemia/reperfusion in- jury（MIRI） induced autophagy in rat. METHODS In vivo MIRI model was established with ischemia 30 rain and reperfusion 120 min, by ligation of left anterior descending coronary artery. TFDM （30 mg · kg -1· d -1 ） and autophagy activator（ 1 mg· kg- 1· d -1 ） or inhibitor（25 mg · kg- 1 ·d- 1 ） pretreatment was given before making the model. The MIRI-induced infarct size, the activities of lac- tate dehydrogenase（ LDH）, creatine kinase isoenzyme（CK-MB） in plasma and apoptosis protein caspase-3 in tissue and the expression level of autophagy-related proteins LC3, Beclin-1 were observed. RESULTS Compared with model group, the experiment revealed that autophagy inhibitor alleviated MIRI-induced myocardial damage by decreasing the infarct size, myocardial enzyme LDH and CK- MB leak; and reducing apoptosis protein caspase-3 activity level. In addition, TFDM pretreatment significantly inhibited the expression of autophagy-related proteins LC3 and Beclin-1. CONCLUSION TFDM shows inhibitory effects on MIRI-induced autophagy, which may play an important role in the protection against MIRI.