丹參酮ⅡA對缺血再灌注大鼠心肌Notch信號通路的影響
發(fā)布時間:2018-06-13 23:10
本文選題:缺血再灌注損傷 + Notch信號通路 ; 參考:《中華中醫(yī)藥學(xué)刊》2017年07期
【摘要】:目的:探討丹參酮IIA對大鼠心肌缺血再灌注損傷是否有保護作用,其機制是否通過調(diào)控Notch信號通路發(fā)揮抗氧化應(yīng)激,進而保護心肌,為丹參酮IIA應(yīng)用于心肌缺血再灌注損傷治療提供分子生物學(xué)依據(jù)。方法:將32只SD大鼠隨機分為4組:正常組、I/R組、DAPT+I/R組、丹參酮IIA+I/R組,每組8只。采用麻醉大鼠冠脈結(jié)扎再松開法,制備大鼠心肌缺血再灌注模型。正常組:平衡灌注120 min;I/R組:平衡灌注15 min,結(jié)扎冠脈30 min,再灌60 min;DAPT+I/R組:平衡灌注15 min,結(jié)扎30 min,DAPT灌注20 min,再灌60 min;丹參酮IIA+I/R組:平衡灌注15 min,結(jié)扎30 min,丹參酮IIA灌注20 min,再灌60 min。檢測各組大鼠心肌組織內(nèi)活性氧水平及乳酸脫氫酶的含量。用Real-time PCR檢測Notch信號通路受體Notch1和下游信號轉(zhuǎn)錄分子Hes1及缺氧誘導(dǎo)因子1α(HIF-1α)mRNA的表達。Western blot檢測Notch1,Hes1,HIF-1α蛋白的表達。結(jié)果:與正常組比較,I/R模型組心肌內(nèi)ROS水平、LDH含量顯著升高(P0.001),Notch1、Hes1、HIF-1α的mRNA的表達明顯增高(P0.001)及蛋白的表達也增高。與模型組比較,DAPT處理組、丹參酮ⅡA處理組ROS水平、LDH含量、Hes1、HIF-1α的mRNA的表達明顯下降(P0.001),DAPT處理組、丹參酮ⅡA處理組Notch1mRNA的表達下降(P0.01,P0.05),與模型組比較,Notch1,Hes1,HIF-1α蛋白的表達也有所下降。結(jié)論 :丹參酮ⅡA通過抑制Notch信號通路,繼而抗氧化應(yīng)激反應(yīng),發(fā)揮對大鼠心肌缺血再灌注損傷的保護作用。
[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 偽 mRNA. Western blot was used to detect the expression of HIF-1 偽 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 偽 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 偽 in tanshinone 鈪,
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