Research Article

血清同型半胱氨酸水平与载脂蛋白M的负相关性

卷 19, 期 2, 2019

页: [120 - 126] 页: 7

弟呕挨: 10.2174/1566524019666190308115624

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: 同型半胱氨酸,载脂蛋白男,脂质代谢,PI3K,高同型半胱氨酸血症,心血管疾病。

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