Published
2026-04-09
Section
Articles
How to Cite
糖皮质激素受体协同有机渗透剂代谢在 Dahl 盐敏感大鼠高血压发病机制中的作用机制
张 悦
西安培华学院
马 怀芬
西安培华学院
孟 婷婷
西安培华学院/西安交通大学
DOI: https://doi.org/10.59429/xjjz.v8i1.13446
Keywords: 糖皮质激素受体（GR）；有机渗透剂；Dahl 盐敏感大鼠；高血压；作用机制
Abstract
目的：探讨当膳食盐摄入量持续性增加后，引起交感神经兴奋、糖皮质激素受体过度激活，调控肾脏积累大量可变量的甘油磷酸胆碱、肌醇、甜菜碱、牛磺酸和山梨醇等有机渗透剂维持渗透压平衡。有机渗透剂合成需要消耗氨基酸，尤其是 L- 丝氨酸失衡，导致肾损伤与血压升高之间的病理生理学机制。方法：选取健康雄性 Dahl 盐敏感大鼠共 32 只，鼠龄 8 周 +，体重 330 ± 10g，分为 0.4% NaCl 正常盐饮食、8% NaCl 高盐饮食组、8% NaCl 高盐饮食 +3 g/L 丝氨酸干预组、8% NaCl 高盐饮食 +0.5ml/100g 地塞米松干预组。喂养持续 6 周后，采用水合氯醛（300 mg/kg）腹腔麻醉大鼠，然后处死大鼠取肾脏并分离出肾皮质和肾髓质部分。结果：地塞米松干预促进 SS 大鼠的摄食、饮水行为，诱导的血压升高，丝氨酸干预显著降低了 SS 大鼠高盐饮食诱导的血压升高，并改善了肾的代谢功能。源于高盐饮食和丝氨酸干预改变了 SS 大鼠肾脏的代谢模式，其差异代谢物和差异代谢通路主要富集在氨基酸代谢，引起谷胱甘肽和一氧化氮合成关键底物氨基酸水平显著升高，使得肾脏谷胱甘肽系统抗氧化防御能力和肾髓质 NO 水平升高，从而改善肾脏 NO 和氧化还原代谢失衡，降低高盐诱导的血压升高。结论：糖皮质激素受体（Glucocorticoid Receptor, GR）是介导糖皮质激素生理及病理效应的核心分子，盐敏感大鼠 GR 表达激活后，会影响NO 水平及 NOS 酶活性，当丝氨酸干预后却提高了 SS 大鼠肾脏有机渗透剂甘油磷酸胆碱水平，改善了高盐饮食引起的氨基酸代谢异常，进一步提升肾脏 NO 和氧化还原代谢失衡和氧化应激状态，从而降低盐敏感高血压的发生。
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