斯钙素-1在慢性阻塞性肺疾病平滑肌增殖中的作用研究

Effect of Stanniocalcin-1 on proliferation of airway smooth muscle in mice with chronic obstructive pulmonary disease

目的探讨斯钙素-1(Stanniocalcin-1,STC1)对慢性阻塞性肺疾病(COPD)平滑肌增殖的影响及STC1在COPD气道重塑中的作用。方法采用臭氧暴露法构建COPD小鼠模型,选取BALB/c雌性小鼠24只,将小鼠随机分为4组:1周空气对照组(简称1周空气组)、1周臭氧暴露组(简称1周臭氧组)、3周空气对照组(简称3周空气组)、3周臭氧暴露组(简称3周臭氧组),每组6只。HE染色观察肺部炎症、肺泡间距及基底膜厚度。采用免疫组织化学法(简称免疫组化)检测小鼠肺组织α-平滑肌动蛋白(α-SMA)及STC1表达。采用2%及10%胎牛血清刺激人原代平滑肌细胞增殖,外源加入重组STC1(rhSTC1)处理平滑肌细胞,EdU染色检测平滑肌细胞增殖。结果臭氧暴露诱导小鼠肺部炎症、肺气肿及气道重塑发生(肺组织基底膜增厚及平滑肌细胞标志物α-SMA表达增加)。STC1主要表达在支气管上皮顶端膜,且在COPD小鼠中表达升高(P<0.05),但随着臭氧暴露3周,肺组织STC1较α-SMA表达下降(P<0.05)。外源加入rhSTC1抑制了平滑肌细胞增殖(P<0.01)。结论支气管上皮表达的STC1能够抑制平滑肌细胞增殖,外源给予足量的STC1可能延缓COPD气道重塑的发生。

Objective To investigate the effect of Stanniocalcin-1 (STC1) on the proliferation of airway smooth muscle and explore the possible role of STC1 in the airway remodeling in the mice with chronic obstructive pulmonary disease (COPD).Methods COPD mice model was established by ozone (O 3) exposure.Twenty-four BALB/c female mice were randomly divided into four groups ( n =6): 1-week control (1WC) group,1-week O 3 exposed (1WO 3) group,3-week control (3WC) group and 3-week O 3 exposed (3WO 3) group.Hematoxylin-eosin (HE) staining was employed to observe the pulmonary inflammation,the alveolar spacing and the basement membrane thickness.Immunohistochemistry technique was used to detect the expression of α-SMA and STC1 in the lung tissues of the mice.Simultaneously,human airway smooth muscle cells (HASMCs) were stimulated by 2% and 10% FBS,respectively.The HASMCs were then treated with recombinant STC1 (rhSTC1).The proliferation of HASMCs was detected by EdU staining.Results O 3 exposure could induce pulmonary inflammation,emphysema and airway remodeling in the mice (basement membrane thickening and increased expression of smooth muscle cell marker α-SMA).Immunohistochemical analysis demonstrated that STC1 expression showed intense staining in the apical membrane of the bronchial epithelial cells and was increased in the O 3-exposed mice.However,with O 3 exposure for 3 weeks,the expression of STC1 in the lung tissues decreased compared with that of α-SMA.And rhSTC1 added the inhibition of the proliferation of smooth muscle cells.Conclusion STC1 expression in the bronchial epithelium can inhibit the proliferation of airway smooth muscle cells.Adequate STC1 administration may delay the occurrence of airway remodeling in the mice with COPD.