活性维生素D缺乏导致脑内加压素表达上调和脑血管功能损伤

Active vitamin D deficiency resulting in brain vasopressin increment and cerebrovascular dysfunction

目的 :本研究探讨1,25二羟维生素D3[1,25(OH)_2D_3]缺乏在小鼠高血压发病的病理进程中对脑内加压素(VP)表达和脑血管功能的影响。方法:运用尾动脉压体积描记法、免疫组织化学、离体微血管压力肌动描记法分析和比较2月龄25羟化维生素D 1α羟化酶基因敲除[1α(OH)ase^(-/-)]小鼠和同窝野生型小鼠的平均动脉血压、脑内VP的表达和脑微血管反应性的变化。结果:1α(OH)ase^(-/-)小鼠出现高血压表型,下丘脑室旁核和视上核VP表达都高于同窝野生型小鼠,大脑后动脉对乙酰胆碱的舒血管反应和对一氧化氮合酶抑制剂L-硝基-精氨酸的缩血管反应较对照组显著降低。结论:1,25(OH)_2D_3在高血压发病过程中对脑内神经内分泌和脑血管功能起重要调控作用。

Objective：The aim of this study was to evaluate the influence of 1,25-dihydroxy vitamin D3[1,25（OH）2D3]deficiency on brain vasopressin expression and cerebrovascular function in hypertension. Methods：Mean arterial pressure,brain vasopressin（VP）expression and cerebrovascular reactivity of two-month-old 1-alpha-hydroxylase [1α（OH）ase]gene knockout mice and their wildtype littermates were analyzed and compared using tail-cuff plethysmography,immunohistochemistry and online videomicroscopy.Results：Compared with their wild-type littermates,1α（OH）ase- /-mice showed high mean arterial pressure,increased VP positive neurons in hypothalamus and cerebral arteries featured markedly decreased dilatory responses to acetylcholine（ACh）and a reduced basal production of NO as exemplified by the attenuated diameter decrease during NOS inhibition with L-NNA. Conclusion：l,25（OH）2D3plays an important role in neuroendocrine regulation and cerebrovascular function in hypertensive progression.