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。
Abstract
OBJECTIVE To explore the effects of Dracocephalum total flavonoids(TFDM) on myocardial ischemia/reperfusion injury(MIRI)induced autophagy in rat. METHODS In vivo MIRI model was established with ischemia 30 min 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 lactate 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.
关键词
香青兰总黄酮 /
自噬 /
缺血再灌注损伤
{{custom_keyword}} /
Key words
Dracocephalum total flavonoids /
autophagy /
myocardial ischemia/reperfusion injury
{{custom_keyword}} /
中图分类号：
R965
{{custom_clc.code}}
({{custom_clc.text}})
{{custom_sec.title}}
{{custom_sec.title}}
{{custom_sec.content}}
参考文献
[1] BINDER A, ALI A, CHAWLA R, et al. Myocardial protection from ischemia-reperfusion injury post coronary revascularization [J]. Expert Rev Cardiovasc Ther, 2015, 13(9):1045-1057.
[2] SCHMIDT M R, PRYDS K, BTKER H E. Novel adjunctive treatments of myocardial infarction [J]. World J Cardiol, 2014, 6(6):434-443.
[3] THAPALIA B A, ZHOU Z, LIN X. Autophagy, a process within reperfusion injury:an update [J]. Int J Clin Exp Pathol, 2014, 7(12):8322-8341.
[4] PRZYKLENK K, DONG Y, UNDYALA V V, et al. Autophagy as a therapeutic target for ischaemia/reperfusion injury? Concepts, controversies, and challenges [J]. Cardiovasc Res, 2012, 94(2):197-205.
[5] FAN X M, CAO W J, XING J G, et al. Protective effect of total flavones from Dracocephalum moldavica against myocar-dial ischemia-reperfusion injury in rats [J]. Chin Tradit Pat Med(中成药), 2013, 35(8):1625-1629.
[6] PERROTTA I, AQUILA S. The role of oxidative stress and autophagy in atherosclerosis [J]. Oxid Med Cell Longev, 2015, 2015:130315.
[7] CHEN-SCARABELLI C, AGRAWAL P R, SARAVOLATZ L, et al. The role and modulation of autophagy in experimental models of myocardial ischemia-reperfusion injury [J]. J Geriatr Cardiol, 2014, 11(4):338-348.
[8] ZENG M, WEI X, WU Z, et al. NF-κB-mediated induction of autophagy in cardiac ischemia/reperfusion injury [J]. Biochem Biophys Res Commun, 2013, 436(2):180-185.
[9] WANG F. Mechanism research of Xinfeng Capsule on cardiac and Pulmonary function based on Keap1-Nrf2 /ARE signaling pathways in sjogren′s syndrome patients [D]. Hefei:Anhui University of Traditional Chinese medicine, 2014.
[10] XIE K. Modulating autophagy to influence the cardiac function in a rat model of dilated cardiomyophy [D]. Shanghai:Fudan University, 2013.
[11] XU X N, FANG L H, DU G H. Research progress of bcl-2 regulating autophagy in myocardial ischemia-reperfusion injury [J]. Chin Pharm J(中国药学杂志), 2014 , 49(5):353-356.
[12] MA S, WANG Y, CHEN Y, et al. The role of the autophagy in myocardial ischemia/reperfusion injury [J]. Biochim Biophys Acta, 2015, 1852(2):271-276.
[13] WU Z, ZOU Z, ZOU R, et al. Electroacupuncture pretreatment induces tolerance against cerebral ischemia/reperfusion injury through inhibition of the autophagy pathway [J]. Mol Med Rep, 2015 , 11(6):4438-4446.
[14] HUANG Z, YE B, DAI Z. Curcumin inhibits autophagy and apoptosis in hypoxia/reoxygenation-induced myocytes [J]. Mol Med Rep, 2015, 11(6):4678-4684.
{{custom_fnGroup.title_cn}}
脚注
{{custom_fn.content}}
基金
国家自然科学基金新疆联合基金重点资助项目(U1203204);国家自然科学基金资助项目(81460638,8136071)
{{custom_fund}}
PDF(2180 KB)
