特异性Kv1.3通道阻断剂对大鼠动脉粥样硬化的影响
本文关键词: 动脉粥样硬化 T淋巴细胞 巨噬细胞 Kv.钾通道 细胞因子 钾通道阻滞剂 出处:《中国老年学杂志》2017年02期 论文类型:期刊论文
【摘要】:目的研究特异性Kv1.3通道阻断剂对高脂喂养大鼠主动脉动脉粥样硬化(AS)发生的影响。方法构建AS大鼠模型,Wistar大鼠被随机分为正常对照(Control)组,AS组,AS药物治疗〔AS+Sh K(L5)〕组(n=10)。利用组织病理学方法观察三组大鼠主动脉组织病变;通过实时荧光定量PCR、Western印迹法检测大鼠主动脉组织Kv1.3通道和相关炎症因子表达水平;通过ELISA法检测大鼠外周血炎症因子水平。结果与Control组比较,AS组总胆固醇(TC)、低密度脂蛋白胆固醇(LDL-C)和甘油三酯(TG)水平均显著增高,高密度脂蛋白胆固醇(HDL-C)水平显著降低,而AS组和AS+Sh K(L5)组之间血脂水平均无差异(P0.05)。大鼠主动脉组织HE染色显示AS组大鼠主动脉内膜增厚,中层平滑肌排列紊乱,炎症细胞浸润;AS+Sh K(L5)组较AS组主动脉组织病变有所减轻。mRNA水平,AS组Kv1.3道通和炎症因子干扰素(IFN)-γ、白介素(IL)-2、IL-10、IL-4、IL-1β的表达量明显高于Control组,而在AS+Sh K(L5)组的表达量明显低于AS组。蛋白水平中AS组Kv1.3道通和炎症因子(IFN-γ、IL-2和IL-10)的表达量明显高于Control组,而AS+Sh K(L5)组的表达量明显低于AS组。AS组大鼠外周血炎症因子(IL-2、IFN-γ和IL-10)的水平较Control组升高,而AS+Sh K(L5)组较AS组有所降低。结论特异性Kv1.3通道阻断剂Sh K(L5)能有效地抑制免疫细胞的活化,降低炎症因子的表达水平,从而减轻病变血管组织的炎症反应,同时可降低外周血炎症因子的水平,特异性Kv1.3通道阻断剂Sh K(L5)对AS的发生有一定的抑制作用。
[Abstract]:Objective to study the effect of specific Kv1.3 channel blocker on the development of atherosclerosis in aorta of high-fat fed rats. The pathological changes of aorta in three groups were observed by histopathological method. The expression of Kv1.3 channels and related inflammatory factors in rat aorta was detected by real-time quantitative PCR Western blot. Results compared with Control group, the levels of TC, LDL-C and TG in as group were significantly higher than those in Control group. However, there was no difference in blood lipid levels between as group and as Sh KnL5 group (P 0.05). The results of HE staining showed that the aortic intima was thickened and the medial smooth muscle was disordered in as group. The expression of Kv1.3, IFN- 纬 and IL-10 IL-10 IL-4- 尾 in as group was significantly higher than that in Control group, and the expression of IL-4 尾 in as group was significantly higher than that in as group (P < 0.05), and the expression of IL-4 尾 was significantly higher in AS-Sh Kh Kh L5 group than that in Control group, and the expression of IL-10 IL-4 尾 was significantly higher in as group than that in Control group. However, the expression of Kv1.3, IFN- 纬, IL-2 and IL-10 in as group was significantly lower than that in as group, and the protein level in as group was significantly higher than that in Control group, and the expression of IFN- 纬 -IL-2 and IL-10 in as group was significantly higher than that in Control group. However, the expression of IL-2IFN- 纬 and IL-10 in as Sh KnL5) group was significantly lower than that in as group. The levels of IFN- 纬 and IL-10 in peripheral blood of as group were significantly higher than those of Control group. Conclusion the specific Kv1.3 channel blocker (Sh KnL 5) can effectively inhibit the activation of immune cells and reduce the expression of inflammatory cytokines, thus reducing the inflammatory response of the diseased vascular tissues. At the same time, the level of inflammatory factors in peripheral blood was decreased, and the specific Kv1.3 channel blocker Sh KKN L5 had a certain inhibitory effect on the occurrence of as.
【作者单位】: 十堰市太和医院湖北医药学院附属太和医院;厦门大学附属中山医院厦门心脏中心;
【分类号】:R543.5
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