Sunitinib对哮喘气道重塑小鼠PDGFR-β磷酸化和MMP-9表达的影响

Effect of Sunitinib on Expressions of p-PDGFR-β and MMP-9 in Asthmatic Mice with Airway Remodeling

目的:探讨sunitinib对支气管哮喘气道重塑的干预作用及可能的作用机制。方法:BALB/c小鼠随机分为正常对照组、哮喘气道重塑组、sunitinib干预组。鸡卵清蛋白致敏和激发建立哮喘小鼠气道重塑模型;收集支气管肺泡灌洗液(BALF)做细胞计数;取右肺组织行苏木精-伊红(HE)染色和Masson三色染色;免疫沉淀(IP法)测定小鼠肺组织PDGFR-β受体磷酸化及westernblo(tWB)法检测MMP-9蛋白质的表达。结果:HE和Masson三色染色提示哮喘组黏膜下层和平滑肌增厚、气道管腔狭窄、胶原纤维增生、大量炎症细胞浸润,sunitinib干预组上述改变较哮喘组为轻;哮喘组BALF中炎症细胞总数和嗜酸性粒细胞(EOS)计数在哮喘组表达较对照组为高(P<0.05),而sunitinib组低于哮喘组(P<0.05);PDGFR-β受体的磷酸化和MMP-9的表达在哮喘组表达较对照组为高(P<0.01),而sunitinib干预组表达量低于哮喘组(P<0.01)。结论:sunitinib能够抑制哮喘小鼠PDGFR-β的磷酸化和MMP-9表达,减轻气道炎症反应、延缓气道重塑进程。

Objective： To investigate the effects of sunitinib on asthmatic airway remodeling and its possible mechanism. Methods： BALB/c mice were randomly divided into three groups： normal group, asthmatic airway remodeling group and sunitinib intervention group. All the mice were sensitized and challenged with ovalbumin （OVA） to establish the asthmatic model. Bronchoalveolar lavage fluid （BALF） cell count and differential were carried out. The right lungs were isolated and stained with haematoxylin and eosin （HE） and Masson＇s trichrome. Expression of phosphorylated-PDGFR-β （p-PDGFR-β） was examined by immuno precipitation（IP）, while MMP-9 expression was examined by Western blot analysis. Results： HE and Masson＇s trichrome staining showed that there were bronchial smooth muscle hypertrophy, submucosa incrassation, airway stenosis, collagen fiber increase and mass inflammatory cells infiltration in asthmatic group. In sunitinib intervention group, the above mentioned symptoms were much more ameliorated. The amounts of total leucocytes and eosinophils in BALF were significantly increased in asthmatic group （P〈0.05）, compared with normal group. While the amounts of total leucocytes and eosinophils in BALF in therapeutic group was lower than that of asthmatic group （P〈0.05）. The protein expression level ofp-PDGFR-β and MMP-9 in asthmatic group was higher than that of the normal group （P〈0.01）, but it was decreased in therapeutic group （P〈0.01）. Conclusion： Sunitinib could inhibit the expression ofp-PDGFR-β and MMP-9, thereby relieve airway in-flammation and delay the process of airway remodeling.