胃肠干预拮抗盐敏感性高血压的机制研究

High salt-intake is an important cause of hypertension. The percent of salt-sensitive hypertension is up to 50% in China and less salt-intake lead to lower blood pressure. Gastrointestinal nerve can regulate intestinal mucosal absorption of sodium through the sodium-hydrogen exchanger, but lack of in-depth study. We found that hypertensive rat showed reduced sympathetic activity and patients decreased urinary sodium excretion after gastric bypass surgery. To this end, we propose the following theoretical assumptions: after gastric bypass surgery, because the food transport pathway and gastrointestinal pressure were changed, gastrointestinal sympathetic nervous system activity decreased causing level of neurotransmitters production secreted from gastrointestine, such as catecholamine, were reduced, leading to inhibition of NaCl absorption by NHE and treatment of salt-sensitive hypertension, through cAMP/Ca2+ and other messenger molecules. The project intends to adopt Dahl salt-sensitive hypertensive rats as the objects, study with blood pressure, vascular structure and function, excitability of the sympathetic nervous system, expression and function of gut mucosal sodium hydrogen exchange and so on in rats after gastric bypass surgery, to clarify the molecular mechanisms of intestinal mucosal sodium hydrogen exchange in the pathogenesis of salt-sensitive hypertension, provide a basis for intervention in hypertension of the gastrointestinal tract.

高盐摄入是高血压的主要危险因素，我国高血压患者中50%属盐敏感性，减少食盐能降低血压。胃肠道神经能调控的肠道粘膜钠氢交换蛋白（NHE）在吸收钠盐中有重要作用，但如何减少钠盐吸收尚缺乏研究。我们发现胃肠转流术后，高血压大鼠交感神经活性降低、临床人群尿钠排出减少。为此，我们提假设：胃肠转流术后食物转运通路、胃肠道压力改变，胃肠交感神经系统活性降低，引起胃肠儿茶酚胺物质等神经递质水平产生减少，使cAMP/Ca2+等信号分子介导的NHE对钠盐吸收减少，从而防治盐敏感性高血压。本项目拟采用Dahl盐敏感高血压大鼠为对象，研究胃肠转流术对大鼠血压、血管结构和功能、交感神经兴奋性、肠道粘膜NHE蛋白功能等作用，阐明肠道粘膜NHE在盐敏感性高血压发病中的机制，为高血压的胃肠道干预提供依据。

目前，我国高血压患者已超过 2 亿，高血压已成为我国最重要的心血管病危险因素。高盐摄入是高血压的主要危险因素，我国高血压患者中50%属盐敏感性，减少食盐能降低血压。本项目采用Dahl盐敏感高血压大鼠为对象，研究胃转流术对大鼠血压、血管结构和功能、交感神经系统、肠道粘膜钠氢交换蛋白（NHE）功能等的影响，阐述胃肠干预拮抗盐敏感性高血压的机制，为高血压的胃肠道干预提供依据。我们通过研究发现胃转流术可以显著降低Dahl盐敏感高血压大鼠的血压，并且降压效果是独立于体重之外的；同时胃转流术还可以改善Dahl盐敏感高血压大鼠的胰岛素抵抗，改善Dahl盐敏感高血压大鼠的血管舒张功能。进一步研究发现胃转流术可能降低Dahl盐敏感高血压大鼠腹腔外周交感神经放电活动，降低Dahl盐敏感高血压大鼠在寒冷应激情况下的血压心率变化，抑制交感神经系统活性。本研究还发现胃转流术显著减少Dahl盐敏感高血压大鼠胃肠道的钠盐吸收，胃转流术后Dahl盐敏感高血压大鼠肠道NHE表达显著减少。我们的研究证实胃肠干预可以作为防治盐敏感性高血压的新靶点。这些研究结果共发表SCI论文1篇，另有1篇SCI论文在投，1篇中文核心期刊论文修回，在此期间共培养博士研究生1名。在此基础上派遣组内人员多次参加国内学术交流.按照基金申请标书计划圆满完成研究目标,扩大了本课题组的学术影响力，圆满的完成了计划任务。