首页> 外文期刊>American Journal of Physiology >Tempol therapy attenuates medial smooth muscle cell apoptosis and neointima formation after balloon catheter injury in carotid artery of diabetic rats.
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Tempol therapy attenuates medial smooth muscle cell apoptosis and neointima formation after balloon catheter injury in carotid artery of diabetic rats.

机译:Tempol疗法可减轻糖尿病大鼠颈动脉球囊导管损伤后的内侧平滑肌细胞凋亡和新内膜形成。

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Accumulating data support the hypothesis that reactive oxygen species (ROS) play a critical role in the vascular complications observed in diabetes. However, the mechanisms of ROS-mediated vascular complications in diabetes are not clear. We tested the hypothesis that ROS-mediated increase in proapoptotic factor Bax expression leads to medial smooth muscle cell (SMC) apoptosis that is associated with neointima formation. We used a fructose-rich diet for 4 wk to model Type 2 diabetes in rats. SOD mimetic membrane-permeable 4-hydroxy-2,2,6,6,-tetramethylpiperidine-1-oxyl (Tempol, 1 mM) was administered in drinking water to scavenge superoxide starting 1 day before surgery and continued during the duration of the experiment. Vascular injury resulted in a significant increase in medial SMC apoptosis that was associated with neointima formation. The number of medial SMC positive for Bax immunostaining significantly increased in injured arteries compared with uninjured arteries. Superoxide scavenging by Tempol treatment inhibited both the Bax-positive index as well as the apoptotic index of medial SMC in response to vascular injury. Tempol treatment inhibited apoptotic loss of medial SMC, thus increasing their density in the injured arteries. These alterations in the media were associated with a marked decrease in neointima formation in injured arteries. We conclude that Bax expression may play an important role in vascular SMC apoptosis and, finally, that this regulatory mechanism is redox sensitive.
机译:越来越多的数据支持以下假设:活性氧(ROS)在糖尿病中观察到的血管并发症中起着至关重要的作用。然而,ROS介导的糖尿病血管并发症的机制尚不清楚。我们测试了ROS介导的促凋亡因子Bax表达增加导致与新内膜形成相关的内侧平滑肌细胞(SMC)凋亡的假说。我们在4周内使用了富含果糖的饮食来模拟大鼠的2型糖尿病。在手术前1天开始在饮用水中施用SOD模拟膜可渗透的4-羟基-2,2,6,6,-四甲基哌啶-1-氧基(Tempol,1 mM)清除超氧化物,并在实验期间持续进行。血管损伤导致与新内膜形成相关的内侧SMC凋亡显着增加。与未受伤的动脉相比,受伤的动脉中Bax免疫染色阳性的SMC内侧数目明显增加。 Tempol处理清除超氧化物能抑制Bax阳性指数以及响应血管损伤的内侧SMC的凋亡指数。 Tempol处理可抑制内侧SMC的凋亡,从而增加其在受伤动脉中的密度。介质中的这些改变与受伤动脉中新内膜形成的明显减少有关。我们得出结论,Bax表达可能在血管SMC凋亡中起重要作用,最后,该调节机制对氧化还原敏感。

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