基于PDE-4靶标的桑白皮提取物桑辛素M对小鼠哮喘模型的治疗作用和机制研究

Effect and mechanism of PDE-4 inhibitor moracin M extracted from cortex mori radicis in mice with asthma

目的 研究基于磷酸二酯酶4 （PDE-4）靶标的桑白皮提取物桑辛素 M 对小鼠哮喘模型的治疗作用和机制。方法 建立卵蛋白 （OVA）诱导哮喘小鼠模型,造模期间同时给予桑辛素 M（每天54 7mg/kg）灌胃,连续给药4周。造模结束后检测小鼠吸入乙酰甲胆碱激发后的气道反应性,提取小鼠肺组织总蛋白进行双向电泳,对表达差异显著的蛋白点进行鉴定分析。结果 桑辛素 M可显著降低哮喘小鼠气道高反应性,抑制气道嗜酸粒细胞浸润和气道炎症。蛋白质组学实验显示转胶蛋白-2、胞内氯离子通道蛋白5 （CLIC5）、G （o）蛋白-α亚基、二甲基精氨酸二甲基氨基酸水解酶2（DDAH2）4种蛋白在哮喘小鼠肺组织中表达显著下降,其余18种差异蛋白的表达则显著增加,而药物干预可显著抑制哮喘小鼠相关差异蛋白的表达下降或增加。结论 桑白皮提取物桑辛素 M可能通过改善气道上皮功能、舒张气管平滑肌、提高机体抗氧化能力、抑制炎性细胞浸润、抑制气道组织重塑而发挥抗哮喘作用。

Objective To investigate the therapeutic effect and mechanism of moracin M extracted from Cortex Mori Radicis which based on phosphodiesterase-4 （PDE-4） target in asthma mice. Methods Asthma were induced in mice sensitized and challenged by ovalbumin （OVA）, during which moracin M （54.7 mg^1·kg^1·d^1） was orally administered for four weeks. The airway responsiveness of mice after methacholine challenge was measured at the last OVA challenge. Total protein of lung tissue of mice was extracted and analyzed by two-dimensional electrophoresis. The differentially-expressed proteins between normal and asthma groups were further identified. Results Moracin M significantly reduce the airway hyperresponsiveness to methacholine, inhibit the airway eosinophil infiltration and airway inflammation in asthma mice. Proteomics results showed that expressions of transgelin-2, chloride intracellular channel protein 5 （CLICS）, G（o） protein a subunit, dimethy larginine dimethy lamino acid hydrolase 2 （DDAH2） were significantly decreased in lung tissue of asthma mice, while levels of other 18 proteins were increased significantly. Moracin M intervention significantly inhibited the increase or decrease of related differential- expressed proteins in asthma mice. Conclusions Moracin M may be effective on inhibiting asthma by enhancing antioxidant capacity, suppressing the inflammatory cell infiltration and inhibiting airway tissue remodeling.