红花提取物对大鼠心脏缺血再灌注的保护作用及机制研究

Protective Effect And Mechanism of Safflower Extract on Cardiac Ischemia-reperfusion in Rats

关键词:  红花提取物  心脏缺血再灌注  氧化应激  炎症

Key words:  safflower extract  cardiac ischemia reperfusion  oxidative stress  inflammation

摘要:

目的 研究红花提取物（safflower extract，SE）对心脏缺血再灌注损伤（ischemia-reperfusion injury，IRI）的保护作用及作用机制。方法 50只大鼠随机分为假手术组，IRI组，SE 1，2，4 g·kg^-1（以生药量计）组，每组10只。SE组于缺血前30 min，分别腹腔注射对应剂量的SE，假手术组及IRI组分别腹腔给予生理盐水1 mL。IRI组和SE组血管夹夹闭左冠状动脉前降支，30 min后松开血管夹，术后测定各组大鼠左心室内压最大上升（下降）速率（±dp/dtmax）、左心室舒张压（LVDP）、左心室舒张末期压（LVEDP）、心率（HR）。恢复心脏灌注20 min后，收集各组大鼠心脏和血清，检测各组大鼠心脏结构及心肌梗死面积，检测肌酸激酶同工酶（CK-MB）、乳酸酶（LDH）活性、蛋白激酶B抗体（Akt）、磷酸化蛋白激酶B抗体（p-Akt）、磷脂酰肌醇3-激酶抗体（PI3K）、雷帕霉素靶蛋白抗体（m-TOR）、核因子κB（NF-κB）、白介素6（IL-6）、肿瘤坏死因子-α（TNF-α）表达水平。结果 与假手术组相比，IRI组HR、LVDP、±dp/dtmax、LVEDP下降，CK-MB、LDH、Akt、p-Akt、PI3K、m-TOR、NF-κB、IL-6、TNF-α表达水平明显升高，心脏病理结构改变明显。与IRI组相比，SE组HR、LVDP、±dp/dtmax、LVEDP升高，CK-MB、LDH、NF-κB、IL-6、TNF-α表达水平明显降低，Akt、p-Akt、PI3K、m-TOR表达水平明显增加，心脏病理结构改变显著减少。结论 SE对于心脏IRI的保护作用呈现剂量相关性，其作用机制与激活PI3K/m-TOR信号通路，抑制炎症因子释放相关。

Abstract:

OBJECTIVE To study the protective effect and mechanism of safflower extract(SE) on cardiac ischemia reperfusion injury(IRI) in rats. METHODS Fifty SD rats were randomly divided into 5 groups(n=10):sham group, IRI group, and SE 1, 2, 4 g·kg^-1 group(equivalent to raw material). Rats in the sham group and IRI group received saline at 30 min before operation(1 mL, intraperitoneally), SE groups received corresponding dose of SE by intraperitioneal injection. The IRI and SE groups were clamped the left anterior descending coronary artery, and removed the clamp for reperfusion after 30 min. After surgery, the ±dp/dtmax, LVDP, LVEDP, HR of these rats were measured. Restore heart perfusion for 20 min, the rats were sacrificed and collected the myocardial tissues and serum, measured the structures and the area of myocardial infarction. Furthermore, CK-MB, LDH, Akt, p-Akt, PI3K, m-TOR, NF-κB, IL-6, TNF-α levels were evaluated. RESULTS Compared with sham group, the HR, LVDP, ±dp/dtmax, LVEDP were decreased and CK-MB, LDH, Akt, p-Akt, PI3K, m-TOR, NF-κB, IL-6, TNF-α levels were decreased especially in the IRI group. The heart pathological structure had a significant change in the IRI group. Compared with the IRI group, the level of the HR, LVDP, ±dp/dtmax, LVEDP were increased, CK-MB, LDH, NF-κB, IL-6, and TNF-α were increased in SE group. Moreover, the level of the Akt, p-Akt, PI3K and m-TOR were significantly increased. The changes of heart pathological structure was depressed. CONCLUSION SE can protect on cardiac IRI in a dose-dependent manner, and its mechanism related to activat the PI3K/m-TOR signaling pathway, and inhibit the release of inflammatory factors.