银杏总黄酮通过调节自噬减轻大鼠心肌缺血再灌注损伤的研究

摘要

Objective To investigate whether Yinxing leaf total flavonoid could mitigate myocardial ischemia and reperfusion(I /R)in-jury and the possible mechanism.Methods Rats I /R model (ischemia 30 min,then reperfusion 4 h)was used.30 rats were divided into three groups:sham -operation group (SO,n =10),ischemia and reperfusion group (I /R,n =10)and Yinxing leaf total flavonoid treatment group (YLTF +I /R,n =10,100 mg·kg -1 ).Cardiac injury markers (serum creatine(CK),lactate dehydrogenase(LDH), and cTnI),oxidative stress (malondialdehyde (MDA)and superoxide dismutase (SOD))and autophagy markers (beclin-1 and LC3) were detected.Results Compared with SO group,levels of cardiac injury markers (CK,LDH and cTnI)and oxidative stress (MDA and SOD)significantly increased;autophagy was excessively activated in I /R group.Compared with I /R group,Yinxing leaf total fla-vonoid significantly decreased cardiac injury markers'(CK,LDH and cTnI)expression and oxidative stress (MDA expression increased and SOD expression decreased),and suppressed excessive activation of autophagy both beclin-1 level and LC3-Ⅱ/Ⅰ ratio decreased). Conclusions Yinxing leaf total flavonoid could mitigate I /R injury via inhibiting excessive activation of autophagy.It's possible that Yinxing leaf total flavonoid inhibited excessive autophagy via suppressing oxidative stress.%目的：探讨银杏总黄酮是否可以通过调节自噬减轻心肌缺血再灌注（I ／R）损伤以及可能的机制。方法采用大鼠心肌I ／R 模型（缺血30 min，再灌注4 h），雄性 SD 大鼠30只随机分为三组：假手术组（SO 组，n ＝10）、缺血再灌注组（I ／R 组，n ＝10）和银杏总黄酮治疗组（YLTF ＋I ／R 组，n ＝10，100 mg·kg －1，造模前灌胃7 d）。检测心肌损伤标记物肌酸激酶（CK）、乳酸脱氢酶（LDH）和肌钙蛋白 I（cTnI）；检测氧化应激水平，即丙二醛（MDA）和超氧化物歧化酶（SOD）水平；检测自噬蛋白beclin-1和 LC3水平。结果与 SO 组比较，I ／R 可诱导心肌损伤标记物（CK、LDH 和 cTnI）表达升高，氧化应激水平的增加（MDA 表达增加，SOD 表达降低）和自噬的过度激活（LC3-Ⅱ／Ⅰ比值增加，beclin-1表达增加）；与 I ／R 比较，银杏总黄酮可显著的降低心肌损伤标记物（CK、LDH 和 cTnI）的表达、氧化应激水平（MDA 表达降低，SOD 表达增加）和自噬的过度激活（LC3-Ⅱ／Ⅰ比值降低，beclin-1表达减低）。结论银杏总黄酮可以通过抑制过度自噬减轻心肌 I ／R 损伤，这可能与其抑制氧化应激作用有关。