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特異性Kv1.3通道阻斷劑對大鼠動脈粥樣硬化的影響

發(fā)布時間:2018-02-11 02:05

  本文關(guān)鍵詞: 動脈粥樣硬化 T淋巴細胞 巨噬細胞 Kv.鉀通道 細胞因子 鉀通道阻滯劑 出處:《中國老年學雜志》2017年02期  論文類型:期刊論文


【摘要】:目的研究特異性Kv1.3通道阻斷劑對高脂喂養(yǎng)大鼠主動脈動脈粥樣硬化(AS)發(fā)生的影響。方法構(gòu)建AS大鼠模型,Wistar大鼠被隨機分為正常對照(Control)組,AS組,AS藥物治療〔AS+Sh K(L5)〕組(n=10)。利用組織病理學方法觀察三組大鼠主動脈組織病變;通過實時熒光定量PCR、Western印跡法檢測大鼠主動脈組織Kv1.3通道和相關(guān)炎癥因子表達水平;通過ELISA法檢測大鼠外周血炎癥因子水平。結(jié)果與Control組比較,AS組總膽固醇(TC)、低密度脂蛋白膽固醇(LDL-C)和甘油三酯(TG)水平均顯著增高,高密度脂蛋白膽固醇(HDL-C)水平顯著降低,而AS組和AS+Sh K(L5)組之間血脂水平均無差異(P0.05)。大鼠主動脈組織HE染色顯示AS組大鼠主動脈內(nèi)膜增厚,中層平滑肌排列紊亂,炎癥細胞浸潤;AS+Sh K(L5)組較AS組主動脈組織病變有所減輕。mRNA水平,AS組Kv1.3道通和炎癥因子干擾素(IFN)-γ、白介素(IL)-2、IL-10、IL-4、IL-1β的表達量明顯高于Control組,而在AS+Sh K(L5)組的表達量明顯低于AS組。蛋白水平中AS組Kv1.3道通和炎癥因子(IFN-γ、IL-2和IL-10)的表達量明顯高于Control組,而AS+Sh K(L5)組的表達量明顯低于AS組。AS組大鼠外周血炎癥因子(IL-2、IFN-γ和IL-10)的水平較Control組升高,而AS+Sh K(L5)組較AS組有所降低。結(jié)論特異性Kv1.3通道阻斷劑Sh K(L5)能有效地抑制免疫細胞的活化,降低炎癥因子的表達水平,從而減輕病變血管組織的炎癥反應,同時可降低外周血炎癥因子的水平,特異性Kv1.3通道阻斷劑Sh K(L5)對AS的發(fā)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- 緯 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- 緯, 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- 緯 -IL-2 and IL-10 in as group was significantly higher than that in Control group. However, the expression of IL-2IFN- 緯 and IL-10 in as Sh KnL5) group was significantly lower than that in as group. The levels of IFN- 緯 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.
【作者單位】: 十堰市太和醫(yī)院湖北醫(yī)藥學院附屬太和醫(yī)院;廈門大學附屬中山醫(yī)院廈門心臟中心;
【分類號】:R543.5

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