1,25-二羟维生素D_3抑制慢性哮喘模型小鼠肺组织 α-平滑肌肌动蛋白的表达及气道重塑

Inhibition of 1,25-(OH)_2D_3 on the α-SMA expression and airway remodeling in a murine model of chronic asthma

目的:探讨1,25-二羟维生素D3[1,25-(OH)2D3]对慢性哮喘模型小鼠肺组织α-平滑肌肌动蛋白(α-SMA)表达及气道重塑的影响。方法:卵白蛋白致敏激发建立慢性哮喘小鼠模型,将小鼠随机分为对照组、哮喘组及VD组。HE染色及天狼星红染色观察各组气道结构及上皮下纤维化,并用计算机图像分析系统评价各组气道重塑;Western blot法及实时荧光定量PCR法检测各组的α-SMA表达。结果:(1)哮喘组出现炎性细胞浸润增多、上皮细胞脱落、上皮下纤维化及平滑肌细胞层增厚等气道重塑的结构改变,而1,25-(OH)2D3的干预可有效减轻上述病理改变;(2)VD组肺组织α-SMA的mRNA及蛋白表达水平均显著低于哮喘组,但仍高于对照组(P<0.05)。结论:1,25-(OH)2D3能降低哮喘小鼠肺组织α-SMA的表达并有效抑制哮喘气道重塑。

Objective To investigate the effects of 1,25-（OH）2D3 on the expression of eL-smooth muscle actin （α- SMA） and airway remodeling in a routine model of chronic asthma. Methods BALB/c mice were sensitized and challenged with ovalbumin to establish chronic asthmatic model. They were randomly divided into control group, asthma group and VD group （n = 6）. Lung sections from the mice were stained by Hematoxylin and Eosin and Sirius Red, respectively. Morphometric analysis of the stained sections was performed using computerized image analysis system. The expression of α-SMA was detected by western blot and real-time RT-PCR. Results （1） Prominent airway remodeling exsited in the asthma group, including the infiltration of inflammatory cells, epithelial loss, subepithelial collagen deposition and increased airway smooth muscle mass. In contrast, 1,25 - （ OH ） 2D3 treatment attenuated these established structural changes of the airways. （2） The mRNA and protein level of α-SMA in the VD group were both decreased when compared with those in the asthma group （P 〈 0.05）, but they were still higher than those in the control group （P 〈 0.05）. Conclusion 1,25-（OH）2D3 could markedly inhibit the expression of α-SMA, thus alleviating the asthmatic airway remodeling.