1,25-二羟维生素D3对哮喘小鼠气道重塑的干预作用

 目的 探讨1,25-二羟维生素D3(1,25-(OH)2D3,VD)对哮喘小鼠气道重塑及其肺组织中基质金属蛋白酶-9(MMP-9)表达的干预作用及其机制。方法 卵蛋白致敏和激发建立慢性哮喘小鼠模型，BALB / c 小鼠随机分为对照组、哮喘组、地塞米松(DEX）组及VD组。HE 染色观察各组气道结构改变情况；采用计算机图像分析系统评价各组气道重塑情况；采用明胶酶谱法及RT-PCR法检测各组的MMP-9的活性及其mRNA表达水平。结果 ①HE 染色提示哮喘组与对照组相比出现炎性细胞浸润增多、上皮细胞脱落及平滑肌细胞层增厚等气道重塑改变,而DEX组及VD组均可部分逆转上述病理改变；②DEX组及VD组的支气管内壁厚度、平滑肌层厚度和平滑肌细胞核数显著低于哮喘组，但仍高于对照组( P < 0.05)；③DEX组及VD组肺组织MMP-9的活性及其mRNA表达水平均明显低于哮喘组，但仍高于对照组 ( P < 0.05) 。结论 VD可显著减轻哮喘气道重塑的病理改变；并可通过部分抑制肺内 MMP-9的表达来延缓气道重塑进程。

Effects of 1,25-(OH)2D3 and dexamethasone on airway remodeling in model murine of chronic asthma

Objective To investigate the effects of 1,25-(OH)2D3 on airway remodeling and the expression of matrix metalloprotease-9 (MMP-9) in a murine model of chronic asthma, and to explore the potential mechanism of 1,25-(OH)2D3 in the treatment of asthma.Methods BALB/c mice were sensitized and challenged with ovalbumin to establish the chronic asthmatic model.They were randomly divided into four groups: control group, asthma group, dexamethasone (DEX) group and VD group.The characteristic airway inflammation and alteration of airway structure were detected by HE staining. Morphometric analysis of the stained sections was performed using computerized image analysis system.The expression of MMP-9 in both activity and mRNA level was detected by gelatin zymograph and RT-PCR, respectively.Results (1)The infiltration of inflammatory cells, epithelial loss, smooth muscle cell layer thickening were decreased in DEX group and VD group when compared with those in asthma group(P<0.05), but these changes were both more significant than those in the control group(P<0.05); (2)WAm /Pbm、WAi/Pbm and N/Pbm decreased significantly in VD group when compared with those in asthma group(P<0.05), but they were still higher than those in the control group (P<0.05); (3)The activity and mRNA level of MMP-9 in VD group was decreased when compared with those in asthma group(P<0.05), but it was still higher than those in the control group(P<0.05). Conclusions Intervention with 1,25-(OH)2D3 and dexamethasone could markly alleviate the asthmatic airway remodeling and partly restore of appropriate structure of airway wall.It could also lower the expression of MMP-9 in the lung tissue on asthmatic condition,thus delay the process of airway remodeling.