丹参酮ⅡA对缺血再灌注大鼠心肌Notch信号通路的影响
发布时间:2018-06-13 23:10
本文选题:缺血再灌注损伤 + Notch信号通路 ; 参考:《中华中医药学刊》2017年07期
【摘要】:目的:探讨丹参酮IIA对大鼠心肌缺血再灌注损伤是否有保护作用,其机制是否通过调控Notch信号通路发挥抗氧化应激,进而保护心肌,为丹参酮IIA应用于心肌缺血再灌注损伤治疗提供分子生物学依据。方法:将32只SD大鼠随机分为4组:正常组、I/R组、DAPT+I/R组、丹参酮IIA+I/R组,每组8只。采用麻醉大鼠冠脉结扎再松开法,制备大鼠心肌缺血再灌注模型。正常组:平衡灌注120 min;I/R组:平衡灌注15 min,结扎冠脉30 min,再灌60 min;DAPT+I/R组:平衡灌注15 min,结扎30 min,DAPT灌注20 min,再灌60 min;丹参酮IIA+I/R组:平衡灌注15 min,结扎30 min,丹参酮IIA灌注20 min,再灌60 min。检测各组大鼠心肌组织内活性氧水平及乳酸脱氢酶的含量。用Real-time PCR检测Notch信号通路受体Notch1和下游信号转录分子Hes1及缺氧诱导因子1α(HIF-1α)mRNA的表达。Western blot检测Notch1,Hes1,HIF-1α蛋白的表达。结果:与正常组比较,I/R模型组心肌内ROS水平、LDH含量显著升高(P0.001),Notch1、Hes1、HIF-1α的mRNA的表达明显增高(P0.001)及蛋白的表达也增高。与模型组比较,DAPT处理组、丹参酮ⅡA处理组ROS水平、LDH含量、Hes1、HIF-1α的mRNA的表达明显下降(P0.001),DAPT处理组、丹参酮ⅡA处理组Notch1mRNA的表达下降(P0.01,P0.05),与模型组比较,Notch1,Hes1,HIF-1α蛋白的表达也有所下降。结论 :丹参酮ⅡA通过抑制Notch信号通路,继而抗氧化应激反应,发挥对大鼠心肌缺血再灌注损伤的保护作用。
[Abstract]:Aim: to investigate the protective effect of tanshinone IIA on myocardial ischemia-reperfusion injury in rats, and whether it can protect myocardium by regulating Notch signaling pathway. To provide molecular biological basis for the application of tanshinone IIA in the treatment of myocardial ischemia reperfusion injury. Methods: Thirty-two Sprague-Dawley rats were randomly divided into 4 groups: normal group (n = 8), I / R group (n = 8) and Tanshinone IIA / R group (n = 8). The myocardial ischemia reperfusion model was established by ligating and releasing coronary artery in anesthetized rats. Normal group: balanced perfusion 120 min I / R group: balanced perfusion 15 min, ligation of coronary artery 30 min, reperfusion 60 min DAPT I / R group: balanced perfusion 15 min, ligation 30 min DAPT 20 min, reperfusion 60 min; tanshinone IIA IR group: balanced perfusion 15 min, ligation 30 min, tanshinone IIA 30 min The rats were perfused for 20 minutes and then for 60 minutes. The levels of reactive oxygen species (Ros) and lactate dehydrogenase (LDH) in myocardium were measured. Real-time PCR was used to detect the expression of Notch1, Hes1, Hes1 and HIF-1 伪 mRNA. Western blot was used to detect the expression of HIF-1 伪 protein. Results: compared with the normal control group, the Ros level and LDH content in the myocardium of the I / R model group were significantly higher than those in the control group. The mRNA expression of Hes1HIF-1 伪 and the protein expression were significantly increased in the I / R model group. Compared with the model group, the mRNA expression of Ros level LDH and Hes1HIF-1 伪 in tanshinone 鈪,
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