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Research Article

腺相关病毒9介导的TLR4小RNA干扰通过抑制大鼠NF-κB和MAPK信号通路减轻心肌缺血和再灌注损伤

卷 19, 期 2, 2019

页: [127 - 135] 页: 9

弟呕挨: 10.2174/1566524019666190311122521

价格: $65

摘要

背景：尽管进行了深入研究，仍然需要有效的心肌I / R损伤治疗方法。目的：探讨腺相关病毒9（AAV9）介导的TLR4小干扰RNA治疗心肌缺血再灌注（I / R）损伤及其对NF-κB和MAPK信号通路的影响。 方法：将大鼠分为3组，即假手术组，AAV9-siRNA对照组和AAV9-TLR4 siRNA组。通过尾部注射siRNA溶液或生理盐水。然后建立大鼠心肌I / R损伤模型。 HE染色和TUNEL染色比较三组心肌细胞的病理变化。免疫组织化学染色和蛋白质印迹用于检测siRNA干扰下的TLR4表达。通过ELISA商业试剂盒测定血清炎症因子（IL-1β，TNF-α）的表达。确定MAPK（p38，JNK 1/2）和NF-κB（p65）信号传导途径中的关键蛋白质以鉴定TLR4 siRNA功能机制。 结果：心肌荧光显微图像显示AAV9介导的siRNA被有效转染到心肌中，与阴性对照组相比，AAV9-TLR4 siRNA可降低I / R损伤后的梗死面积（P <0.05）。 siRNA干扰显着降低TLR4蛋白表达（P <0.001）。 TLR4基因沉默组中凋亡相关因子BCL-2表达增加，而Bax表达减少。 Bax / BCL-2比率也降低，表明对心肌细胞具有保护作用。 TLR4基因沉默组的炎症因子低于siRNA对照组（P <0.001）。 MAPK和NF-κB信号通路在心肌I / R损伤中被激活;然而，这两种信号通路中的主要蛋白质在TLR4 siRNA干扰后下调，差异显着（P <0.05）。 结论：AAV9-TLR4 siRNA通过抑制MAPK和NF-κB信号通路对心肌I / R损伤有积极作用，可作为心肌I / R损伤的潜在治疗方法。

关键词: 心肌I / R损伤，AAV9-TLR4 siRNA，MAPK，NF-κB，炎症，缺血。

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