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>Pretreatment with Total Flavonoid Extract from Dracocephalum Moldavica L. Attenuates Ischemia Reperfusion-induced Apoptosis
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Pretreatment with Total Flavonoid Extract from Dracocephalum Moldavica L. Attenuates Ischemia Reperfusion-induced Apoptosis
We previously demonstrated the cardio-protection mediated by the total flavonoid extracted from Dracocephalum moldavica L. (TFDM) following myocardial ischemia reperfusion injury (MIRI). The present study assessed the presence and mechanism of TFDM-related cardio-protection on MIRI-induced apoptosis in vivo. Male Sprague-Dawley rats experienced 45-min ischemia with 12 h of reperfusion. Rats pretreated with TFDM (3, 10 or 30 mg/kg/day) were compared with Sham (no MIRI and no TFDM), MIRI (no TFDM), and Positive (trapidil tablets, 13.5 mg/kg/day) groups. In MIRI-treated rats, high dose-TFDM (H-TFDM) pre-treatment with apparently reduced release of LDH, CK-MB and MDA, enhanced the concentration of SOD in plasma, and greatly reduced the infarct size, apoptotic index and mitochondrial injury. H-TFDM pretreatment markedly promoted the phosphorylation of PI3K, Akt, GSK-3β and ERK1/2 in comparison with the MIRI model group. Western blot analysis after reperfusion also showed that H-TFDM decreased release of Bax, cleaved caspase-3, caspase-7 and caspase-9, and increased expression of Bcl-2 as evident by the higher Bcl-2/Bax ratio. TFDM cardio-protection was influenced by (PI3K inhibitor) and PD98059 (ERK1/2 inhibitor). Taken together, these results provide convincing evidence of the benefit of TFDM pretreatment due to inhibited myocardial apoptosis as mediated by the PI3K/Akt/GSK-3β and ERK1/2 signaling pathways.
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机译:先前我们证明了心肌缺血再灌注损伤(MIRI)后,从青霉菌(Dracocephalum Moldavica L.)(TFDM)提取的总黄酮介导的心脏保护作用。本研究评估了TFDM相关的心脏保护作用对MIRI诱导的体内细胞凋亡的作用。雄性Sprague-Dawley大鼠经历了45分钟的局部缺血再灌注12h。将用TFDM(3、10或30μmg/ kg /天)预处理的大鼠与假手术(无MIRI和无TFDM),MIRI(无TFDM)和阳性(曲哌地尔片剂,13.5μmg/ kg /天)组进行比较。在MIRI治疗的大鼠中,高剂量的TFDM(H-TFDM)预处理明显降低了LDH,CK-MB和MDA的释放,提高了血浆中SOD的浓度,并大大减少了梗塞面积,凋亡指数和线粒体受伤。与MIRI模型组相比,H-TFDM预处理显着促进了PI3K,Akt,GSK-3β和ERK1 / 2的磷酸化。再灌注后的蛋白质印迹分析还显示,H-TFDM降低了Bax的释放,裂解了caspase-3,caspase-7和caspase-9的表达,并增加了Bcl-2的表达,这由较高的Bcl-2 / Bax比值所证实。 TFDM心脏保护受到(PI3K抑制剂)和PD98059(ERK1 / 2抑制剂)的影响。两者合计,这些结果提供了令人信服的证据,表明TFDM预处理的益处是由于PI3K / Akt /GSK-3β和ERK1 / 2信号通路介导的心肌细胞凋亡抑制。
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