隐丹参酮对老年大鼠脑缺血再灌注损伤的保护作用及机制研究

Protective Effects and Possible Mechanism of Cryptotanshinone in Cerebral Ischemia-reperfusion Injury in Aged Rats

目的:探讨隐丹参酮(cryptotanshinone,CTN)对老年大鼠脑缺血再灌注损伤的保护作用及其可能机制。方法:Longa法制作大鼠中动脉缺血再灌注损伤模型。将SD大鼠随机分为正常对照组(CTL)、缺血再灌注组(I/R)、隐丹参酮低剂量治疗组(CTN1)(2.5mg/kg)和隐丹参酮高剂量治疗组(CTN2)(5mg/kg),对各组大鼠进行神经功能缺损评分,测定脑梗死体积,测定Caspase-3蛋白表达,检测SOD活性、GSH-Px、MDA及NO的含量变化,实时荧光定量PCR法检测脑组织中miR-210的表达。结果:与缺血再灌注组相比,隐丹参酮组可显著降低大鼠神经功能损伤评分、减少脑梗塞体积、显著降低脑组织内氧自由基的生成,提高SOD活性,并降低miR-210的表达,miR-210的表达量由(12.29±2.14)降至(6.91±0.53)(P<0.05)。结论:隐丹参酮对老年大鼠脑缺血再灌注损伤有明显的保护作用,其机制可能部分与减轻氧化应激损伤、抗凋亡和降低miR-210的表达有关。

Objective：To explore the protective effects and possible mechanism of cryptotanshinone in cerebral ischemia-reperfusuion injury in aged rats. Methods：A model of rat cerebral ischemia-reperfusion （I/R） injury based on Longa method was made. The Sprague-Dawley（SD） rats were randomly divided into normal control group（CTL）, I/R group, cryptotanshinone Low-dose（CTN1） treatment group （2.5mg/kg） and cryptotanshinone High-dose（CTN2）treatment group （5mg/kg）. Neurological deficit score was evaluated when rats were allowed to awaken at 6h after operation in each group. Cerebral infarct volume was also determined. Western blot was used to detect the expression of Caspase-3 protein level. The activity of SOD and the concentration of GSH-Px, MDA and NO in brain tissues were performed. The expression of miR-210 was detected by real-time PCR. Results：Compared with the I/ R group, CTN group significantly reduced the neurological deficit scores and infarct volumes. The decrease of oxygen free radical production and the increase of SOD activity in the brain tissues were also observed. Real-time PCR showed that the expression of miR-210 was significantly reduced after cryptotanshinone treatment. CTN2 group＇s expression of miR-210 reduced from （12.29± 2.14） to （6.91±0.53）（P〈0.05）. Conclusion： Results indicated that cryptotanshinone could protect against cerebral I/R injury in aged rats, which may partly attribute to alleviating the oxidative stress injury, anti-apoptosis and the reduction of miR-210 expression.