Zhou Yan, Zhou Xin, Wang Xiaoqiu
Department of Respiratory Medicine, Shanghai First Hospital, Shanghai Jiao Tong University, Shanghai 200080, China.
Allergy Asthma Proc. 2008 May-Jun;29(3):258-67. doi: 10.2500/aap.2008.29.3115.
The active form of 1,25-dihydroxyvitamin D3 [1,25(OH)2D3] regulates calcium homeostasis, immunity, and other physiological processes while its effect in T-helper lymphocyte type 2 models is not very clear. The prevention effect of 1,25(OH)2D3 for allergic asthma in a rat asthma model was investigated. Healthy Wistar rats were randomly divided into four groups: control group, asthma group, drug prevention group, and treatment group. Asthma was induced in rats by sensitization and challenges with ovalbumin (OVA). The drug prevention group and treatment group were given 1,25(OH)2D3 or vitamin D3 on different schedules. The effects of 1,25(OH)2D3 on the development of asthma were analyzed. The airway hyperresponsiveness, the inflammatory cell infiltration in bronchoalveolar lavage (BAL) fluid, and histological changes of lung cells were examined. Nitric oxide production and the expression and activity of induced nitric oxide synthase (iNOS) in the lungs were examined also. Our study showed that 1,25(OH)2D3 reduced the airway inflammatory response in BAL. The concentration of NO and the activity and expression of iNOS in the lungs were decreased in the 1,25(OH)2D3 prevention and treatment groups. The expression of iNOS mRNA and protein levels were dose-dependently attenuated in the presence of 10(-13)-10(-8) mol/L of 1,25(OH)2D3 in alveolar macrophage culture. These findings collectively indicated that 1,25(OH)2D3 lowered many symptoms of inflammatory responses and decreased the expression of iNOS in OVA-induced experimental asthma. 1,25(OH)2D3 could be used as a new therapeutic agent in the treatment of asthma.
1,25 - 二羟基维生素D3[1,25(OH)2D3]的活性形式调节钙稳态、免疫及其他生理过程，但其在2型辅助性T淋巴细胞模型中的作用尚不清楚。本研究探讨了1,25(OH)2D3对大鼠哮喘模型过敏性哮喘的预防作用。将健康的Wistar大鼠随机分为四组：对照组、哮喘组、药物预防组和治疗组。通过卵清蛋白（OVA）致敏和激发诱导大鼠哮喘。药物预防组和治疗组按不同方案给予1,25(OH)2D3或维生素D3。分析1,25(OH)2D3对哮喘发展的影响。检测气道高反应性、支气管肺泡灌洗（BAL）液中的炎性细胞浸润以及肺细胞的组织学变化。同时检测肺组织中一氧化氮的产生以及诱导型一氧化氮合酶（iNOS）的表达和活性。我们的研究表明，1,25(OH)2D3可减轻BAL中的气道炎症反应。1,25(OH)2D3预防组和治疗组肺组织中NO浓度、iNOS活性及表达均降低。在肺泡巨噬细胞培养中，当存在10(-13)-10(-8)mol/L的1,25(OH)2D3时，iNOS mRNA和蛋白水平的表达呈剂量依赖性减弱。这些结果共同表明，1,25(OH)2D3可减轻OVA诱导的实验性哮喘中多种炎症反应症状，并降低iNOS的表达。1,25(OH)2D3可作为治疗哮喘的新型治疗药物。
