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敲除AT1a基因对血管紧张素II受体介导的信号传导作用 |
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祝之明 祝善俊 胡厚祥
【摘要】 目的 研究敲除血管紧张素Ⅱ受体亚型（AT1a）基因对血管紧张素Ⅱ（AngⅡ）信号传导的影响，明确AT1a在血管功能调节中的作用。方法 应用缺乏AT1a基因小鼠的主动脉血管平滑肌细胞（VSMC），采用钙荧光分析技术，观察G蛋白受体偶联和酪氨酸激酶相关的钙离子信号传导通路的变化。结果 敲除AT1a基因，并不影响AngⅡ介导的VSMC钙增加，应用G蛋白拮抗剂和酪氨酸激酶抑制剂均能显著抑制AngⅡ反应。结论 敲除AT1a基因，其他AT1受体亚型能起明显的代偿作用，AT1a受体亚型受G蛋白和酪氨酸激酶信号传导通路共同调节。
【关键词】 信号传递 小鼠，基因摧毁 受体，血管紧张素
Effect of angiotensin II receptor subtype (ATla) knockout on angiotensin II mediated calcium signal transduction pathways ZHU Zhiming, ZHU Shanjun, HU Houxiang. Hypertension Center, Daping Hospital, Third Military Medical University, PLA, Chongqing 400042
【Abstract】 Objective To investigate the effect of ATla gene knockout on angiotensin Ⅱ (Ang Ⅱ) mediated calcium signal transduction pathways and determine the role of ATla gene in the regulation of vascular function.Methods Vascular smooth muscle cells (VSMCs) were obtained from mice that mutant ATla gene and its wild type control. Intracellular calcium signal was observed using Fura-2/AM fluorescent technique. GDP-βS and genestein were used to antagonize G-protein and tyrosine kinase (TK) coupling pathways, respectively.Results Ang Ⅱ mediated calcium signal was ineffective after knockout AT1a gene. Inhibition of G-protein and TK can significantly reduce the response of calcium signal to Ang Ⅱ stimulation in VSMCs from mice.Conclusion Calcium signal was not interrupted by AT1a gene knockout due to compensative effect of other AT1 receptor subtype and AT1 receptor subtypes were regulated by both G-protein and TK coupling signal transduction pathways.
【Key words】 signal transduction mice, knockout receptors, angiotensin
血管紧张素Ⅱ( Ang Ⅱ）在高血压发病中起重要作用, AngⅡ主要与其特异性受体(AT1）结合,通过G蛋白偶联的磷脂酶C(β)和酪氨酸激酶相关的磷脂酶C(γ)信号通路导致细胞内第二信使分子改变,并介导一系列级联反应,使血管张力增高和心血管细胞重塑［1］。AT1分为二个亚型：AT1a和AT1b。大量研究证实，AngⅡ发挥作用主要通过AT1a, 应用特异性AT1a拮抗剂能有效地降低血压及逆转心血管细胞重塑［2］。因此, AT1a基因是重要的高血压相关基因。虽然AT1a在血压及血管结构功能调节中的作用已获充分肯定, 但很难确定AT1a这种作用是只源于AT1a基因的本身, 还是与其他的相关基因共同作用或[1] [2] 下一页
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