孕期哺乳期大鼠补充维生素D3对子代大鼠哮喘模型肺组织维生素D受体表达的影响

目的探讨给予孕期及哺乳期大鼠不同剂量1,25-二羟维生素D3,对其子代大鼠哮喘模型肺组织维生素D受体(VDR)表达的影响。方法雌性Wistar大鼠32只,随机分配到维生素D低、中、高剂量组,在孕期及哺乳期给予不同剂量的1,25-二羟维生素D3,并设对照组。子代大鼠断乳后,各组随机取8只,用卵清蛋白致敏并激发,建立哮喘模型。采用real-time PCR和免疫组织化学方法分别从mRNA和蛋白水平检测子代大鼠VDR的表达。结果与对照组相比,中剂量组子代大鼠支气管痉挛收缩、管壁增厚、管腔内黏液分泌增加、肺部炎症浸润等变化最轻,低剂量组其次,高剂量组反而较对照组严重。免疫组织化学染色显示,与对照组相比,低剂量组和中剂量组子代大鼠的VDR表达明显减少,且中剂量组较低剂量组更明显,差异有统计学意义(P均<0.01);高剂量组的VDR表达则较对照组增多,差异亦有统计学意义(P<0.01)。real-time PCR结果显示,与对照组比较,低剂量组和中剂量组子代大鼠肺组织中VDR mRNA水平降低,而高剂量组的VDR mRNA水平增高,差异均有统计学意义(P<0.01)。结论孕期及哺乳期补充适量维生素D可减少子代大鼠哮喘模型VDR的表达,减轻气道炎症反应,而过量补充维生素D则增加VDR表达,可能加重气道炎症反应。

Vitamin D3 supplementation in pregnant and lactating rats on vitamin D receptor expression in the lung of baby rats with asthma

Objective To investigate the effect of vitamin D supplementation in pregnant and lactating rats on vitamin D receptor(VDR) expression in the lung of baby rats with asthma.Methods Thirty two sexually matured female Wistar rats were randomly divided into low dose group,medium dose group and high dose group.During the gestation and lactation period,rats of each group were given different doses of 1,25-(OH)2D3 while the control group was given normal saline.After the newborn rats were weaned,8 baby rats were chosen from each group randomly.Then the rats were challenged with aerosol ovalbumin to establish the asthma model.The expression of VDR in the lung of baby rats was measured by immunochemistry and real-time PCR.Results Compared with the control group,contraction of bronchial spasm,airway thickening,increasing mucus secretion in the lumen,inflammation in the lung tissue etc.were less serious in the medium dose group,followed by the low dose group.But the inflammation was more serious in high dose group.Compared with the control group,results of immunohistochemistry in lung tissues showed that expression of VDR was decreased in the low dose group and the medium dose group,while an increase was found in the high dose group and the difference was statistically significant(P < 0.01).In addition,the expression of VDR in the medium dose group was significantly lower than that in the low dose group(P < 0.01).The results of real-time PCR showed the expression of VDR mRNA in the lung of baby rats was decreased in the low dose group and the medium dose group compared with the control group,but increased in the high dose group(P < 0.01).Conclusions Appropriate vitamin D supplementation in pregnant and lactation period could decrease the VDR expression and alleviate airway inflammation in the baby rat of asthma models,while overdosing of vitamin D supplementation could increase the VDR expression and aggravate the inflammation in asthma.