沙苑子总黄酮对博莱霉素致大鼠肺纤维化的干预作用及其机制研究

目的探讨沙苑子总黄酮(FAC)对博莱霉素(BLM)所致实验性大鼠肺纤维化的干预作用,并探讨其作用机制。方法采用气管内滴注博莱霉素法制作大鼠肺纤维化模型,并随机分为6组。给予沙苑子总黄酮灌胃(ig)治疗28 d后,腹主动脉放血法处死动物,测定血清和总抗氧化能力(T-AOC)及肺组织中羟脯氨酸(HYP)含量;ELISA的方法检测实验大鼠肺泡灌洗液中IL-1β和IL-6的含量;取固定部位肺组织作HE及Masson染色,进行病理组织学观察;电镜观察大鼠肺组织的超微结构变化;Westen blot法检测沙苑子总黄酮TGF-β/Smad信号通路相关蛋白的表达。结果与模型组相比,沙苑子总黄酮各组大鼠肺组织中HYP含量明显降低(P<0.01或P<0.05),且有剂量依赖趋势;大鼠血清及肺组织中T-AOC增强(P<0.01或P<0.05);肺泡灌洗液中细胞因子IL-1β及IL-6的含量明显降低(P<0.01或P<0.05);组织病理学观察肺泡炎症(P<0.01或P<0.05)及肺组织纤维化(P<0.01或P<0.05)的程度明显减轻;West-ern blot检测结果显示TGF-β/Smad信号通路相关蛋白TGF-β、Smad2、α-SMA含量均明显降低。结论沙苑子总黄酮对博莱霉素致大鼠肺纤维化病变有一定的治疗作用,其作用机制可能与其抑制炎症细胞因子的活化、抗氧化作用、抑制胶原的形成以及调控TGF-β/Smad信号通路有关。

Effects of total flavonoids from astragalus complanatus on bleomycin-induced pulmonary fibrosis in rats and its mechanisms

Aim To observe the effects of total flavonoids from astragalus complanatus(FAC) on bleomycin-induced pulmonary fibrosis in rats and investigate its mechanisms.Methods The pulmonary fibrosis model was replicated by intratracheal injection of bleomycin.SD rats were randomly divided into six groups.After 28 d with FAC treatment by intragastric administration,the animals were sacrificed by abdominal aorta exsanguination.The levels of hydroxyproline(HYP),total antioxidant capacity(T-AOC) in lung tissue and serum were analyzed.The extents of IL-1β and IL-6 in bronchoalveolar lavage fluid were measured by enzymelinked immunoadsordent assay.HE and Masson staining methods were utilized for histopathological examination.The effects of FAC on the expression of transforming growth factor-β(TGF-β),Smad2,α-SMA in lung tissue of rats were assayed by Western blot.Results Compared with the model group,the levels of TAOC in serum were dramatically increased and the level of HYP was decreased remarkably after FAC treatment;IL-1β and IL-6 in bronchoalveolar lavage fluid were decreased significantly;the alveolitis and fibrosis extent were attenuated after FAC treatment,and the levels of associated protein TGF-β,Smad2,α-SMA were decreased significantly.Conclusions FAC can attenuate bleomycin-induced pulmonary fibrosis in rats.The mechanisms might be related with the inhibition of activation of inflammatory cell infiltration,the anti-oxidative damage,the inhibition of collagen formation and the regulation of TGF-β / Smad signal pathway.