DIDS通过PI3-K/Akt途径减弱缺血/再灌注损伤诱导心肌细胞凋亡 |
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引用本文: | 张卫卫,刘艳,师堂旺,刘佳妮,刘艳霞,王晓明.DIDS通过PI3-K/Akt途径减弱缺血/再灌注损伤诱导心肌细胞凋亡[J].心脏杂志,2009,21(3):313-316. |
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作者姓名: | 张卫卫 刘艳 师堂旺 刘佳妮 刘艳霞 王晓明 |
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作者单位: | 第四军医大学西京医院老年病科,陕西 西安 710032 |
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摘 要: | 目的 探讨磷脂酰肌醇3激酶(PI3-K)/蛋白激酶B(Akt)信号通路在DIDS(4,4′-diisothiocyanostilbene-2,2′-disulfonic acid)减弱缺血/再灌注损伤(I/RI)诱导心肌细胞凋亡中的作用。方法 以I/RI诱导心肌细胞凋亡,然后用PI3-K特异性的抑制剂LY294002[22(42吗啉基)282苯基24氢212苯并吡喃242酮]进行干预。实验分为正常对照组、I/RI组、I/RI+DIDS组和I/RI+DIDS+LY294002组。通过噻唑蓝(MTT)比色法、Hoechest-33258染色和半胱天冬蛋白酶(Apo-ONETM Homogeneous Caspase)-3试剂盒以及Western blot分别检测:心肌细胞的存活率(%)、细胞核的形态变化和caspase-3活性、Akt的磷酸化。结果 ①DIDS能够显著抑制I/RI诱导的细胞存活率的下降,抑制凋亡小体的出现,抑制caspase-3的活性的增加(P<0.01)。②用LY294002预处理后,DIDS保护I/RI心肌细胞存活的作用减弱、凋亡小体增加和caspase-3活性明显升高(P<0.01)。③I/RI组与正常对照组Akt磷酸化无明显差异,DIDS能够显著增加I/RI组中Akt蛋白的磷酸化(P<0.01)。用LY294002预处理后,DIDS对I/RI组Akt蛋白磷酸化的影响明显减弱(P<0.01)。结论 DIDS可通过激活PI3-K/Akt信号通路减弱I/RI 诱导的心肌细胞的凋亡。
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关 键 词: | 心肌细胞 缺血/再灌注 凋亡 PI3-K/Akt信号通路 |
收稿时间: | 2008-10-21 |
DIDS Attenuates ischemia/reperfusion injury-induced cardiomyocytes apoptosis through PI3-K/Akt signaling pathway |
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Abstract: | AIM To explore the role of phosphatidylinositol 3′-kinase (PI3-K)/protein kinase B (Akt) signaling pathway during DIDS (4,4′-diisothiocyanostilbene-2,2′-disulfonic acid) inhibited cardiomyocytes apoptosis induced by ischemia/reperfusion injury (I/RI). METHODS Cardiomyocytes apoptosis was induced by I/RI, then it was treated with phosphatidylinositol 3 kinas’ inhibitor LY294002 [22(42-Morpholine) 282 H-24-212 benzopyran 242](specific inhibitor of PI3-K). Experiment was divided into the normal control group, I/RI group, I/RI+DIDS group and I/RI+DIDS+LY294002 group. The cell viability, morphology changes of nucleus and caspase-3 activity, Akt phosphorylation was observed through the MTT colorimetric, Hoechest-33258 staining and caspase (Apo-ONETM Homogeneous Caspase)-3 kit and Western blot. RESULTS ①DIDS was able to markedly inhibit the I/RI indicated by a decline of cell viability, inhibited the emergence of apoptotic bodies, restrained the increase of caspase-3 activity (P<0.01); ②Pretreatment with LY294002, the increase of myocardial cells’ viability, decrease of apoptotic bodies and the increase of caspase-3 activity were significant blocked (P<0.01); ③There was no significant difference of Akt phosphorylation between I/RI group and control. DIDS could dramatically increase Akt phosphorylation in I/RI group (P<0.01); Pretreatment with LY-294002, DIDS’ effect on the Akt phosphorylation in the I/RI group was decreased significantly (P<0.01). CONCLUSION DIDS attenuates I/RI-induced myocardial apoptosis through the activation of PI3K/Akt signaling pathway. |
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