遗传性应激性高血压与下丘脑热敏TRP离子通道基因表达改变有关

I. Voronova, A. A. Tuzhikova, A. L. Markel', T. Kozyreva
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引用次数: 10

摘要

目的:广泛存在的原发性高血压,其性质尚不清楚,需要对正常和高血压的差异进行全面的研究。高血压可能在不同程度上与中枢神经系统功能的改变有关。我们之前的数据显示了正常和高血压大鼠的热反应性差异。热敏TRP(瞬时受体电位)离子通道被认为是热敏性的分子基础,在温度调节中是必不可少的。下丘脑是调节血压和体温的重要大脑结构。本研究旨在探讨正常和高血压大鼠下丘脑不同功能部位热敏TRP离子通道基因的表达。方法:采用雄性遗传性应激性动脉高血压(ISIAH)大鼠和正常血压的Wistar Albino Glaxo (WAG)。采用逆转录聚合酶链反应(RT-PCR)定量方法检测基因表达。结果:正常大鼠与高血压大鼠瞬时受体电位美拉他汀8 (Trpm8)和瞬时受体电位香草素4 (Trpv4)基因表达存在差异。高血压患者下丘脑前部的Trpm8 mRNA水平比正常者低2倍以上。高血压患者下丘脑后侧Trpv4 mRNA水平比前侧高一半,且显著高于正常血压组。在血压正常者中,Trpv4基因在下丘脑的两个部分表达相同。正常和高血压患者下丘脑前后部的差异相似:下丘脑前部Trpm8 mRNA水平比后部高3倍,Trpv1和瞬时受体电位锚蛋白1 (Trpa1) mRNA水平反之亦然。结论:所得数据有助于进一步了解高血压状态的可能分子基础,并阐明所研究的热敏TRP离子通道的某些生理作用。
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Inherited stress-induced hypertension associates with altered gene expression of thermosensitive TRP ion channels in hypothalamus -
Objective: The widespread essential hypertension, of which the nature is still unclear, demands a comprehensive study of the differences between normo- and hypertensives. Hypertension may be associated with changes in the central nervous system functioning, at various levels. Our previous data have shown the differences in thermo-responsiveness of normotensive and hypertensive rats. Thermosensitive TRP (transient receptor potential) ion channels which are considered as a molecular basis of the thermosensitivity are essential for thermoregulation. Hypothalamus is the important brain structure for blood pressure and temperature regulation. The aim of present work was to assess the expression of thermosensitive TRP ion channel genes in functionally different parts of hypothalamus in normo- and hypertensive rats. Methods: Male inherited stress-induced arterial hypertensive (ISIAH) rats and normotensive Wistar Albino Glaxo (WAG) were used. Gene expression was assayed by the quantitative method of reverse transcription-polymerase-chain-reaction (RT-PCR). Results: Differences between normal and hypertensive rats were found in the expression of transient receptor potential melastatin 8 (Trpm8) and transient receptor potential vanilloid 4 (Trpv4) genes. The level of Trpm8 mRNA in the anterior hypothalamus of hypertensives was more than twice lower than in normotensives. In hypertensives, the level of Trpv4 mRNA in posterior hypothalamus was half time higher than in anterior, and significantly higher than in the normotensives. In normotensives, the Trpv4 gene expression was the same in both parts of hypothalamus. Some differences between anterior and posterior hypothalamus were similar in normo- and hypertensives: the level of Trpm8 mRNA in the anterior hypothalamus was three times higher than in the posterior and the levels of Trpv1 and transient receptor potential ankyrin 1 (Trpa1) mRNA, vice versa. Conclusion: The obtained data allow to come closer to understand the possible molecular bases of the status of hypertension and elucidate some aspects of the physiological role of the investigated thermosensitive TRP ion channels.
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