羟基红花黄色素A对肺纤维化小鼠的保护作用

Protective effects of hydroxysafflower yellow A on pulmonary fibrosis in mice

目的:观察羟基红花黄色素A(HSYA)对博来霉素致小鼠肺纤维化的影响及转化生长因子β1(TGF-β1)/Smad信号转导通路的调控。方法:通过鼻腔内一次性滴注博来霉素50μl(15 mg/kg)制备肺纤维化模型。将ICR小鼠随机分为对照组、模型组、HSYA组(6 mg/kg)、地塞米松(Dex)组(3 mg/kg),每组15只。造模次日起,HSYA及Dex组腹腔注射相应药物,对照组、模型组腹腔注射同体积生理盐水,1次/日,连续28 d。4周后处死小鼠并取肺脏,HE及Masson染色观察肺组织病理损伤;免疫组化、RT-qPCR及Western blot检测肺组织中TGF-β1/Smad信号通路表达。结果:与对照组比较,模型组小鼠表现出严重的肺泡炎和肺纤维化;肺组织中的TGF-β1、Smad3 mRNA及蛋白表达明显升高(P<0.01),Smad7 mRNA及蛋白表达明显降低(P<0.01)。与模型组比较,HSYA、Dex组的肺泡炎和肺纤维化程度明显减轻;HSYA、Dex组肺组织中的TGF-β1、Smad3 mRNA及蛋白表达明显降低(P<0.01),Smad7 mRNA及蛋白表达明显升高(P<0.01)。结论:HSYA能够缓解肺纤维化的发病过程,其机制可能与调控TGF-β1/Smad信号通路有关。

Objective:To investigate the effect of hydroxysafflower yellow A(HSYA)on pulmonary fibrosis induced by bleomycin in mice and transforming growth factorβ1(TGF-β1)/Smad signal transduction pathway regulation.Methods:The pulmonary fibrosis model was prepared by intranasal injection of bleomycin 50μl(15 mg/kg).ICR mice were randomly divided into control group,model group,HSYA group(6 mg/kg)and dexamethasone(Dex)group(3 mg/kg),with 15 mice in each group.From the next day of modeling,HSYA and Dex groups were intraperitoneally injected with corresponding drugs,while the control group and model group were intraperitoneally injected with the same volume of normal saline,once a day,for 28 consecutive days.After 4 weeks,the mice were sacrificed and the lungs were collected.HE and Masson staining were used to observe the pathological damage of lung tissue;Immunohistochemistry,RT-qPCR and Western blot were used to detect the expressions of TGF-β1/Smad signaling pathway in lung tissues.Results:Compared with the control group,the model group showed severe alveolitis and pulmonary fibrosis.The mRNA and protein expressions of TGF-β1 and Smad3 in lung tissues were increased significantly(P<0.01),while the mRNA and protein expressions of Smad7 were decreased significantly(P<0.01).Compared with the model group,the degree of alveolitis and pulmonary fibrosis in the HSYA and Dex groups was reduced significantly.The mRNA and protein expressions of TGF-β1 and Smad3 in lung tissues of HSYA and Dex groups were decreased significantly(P<0.01),while the mRNA and protein expressions of Smad7 were increased significantly(P<0.01).Conclusion:HSYA can alleviate the pathogenesis of pulmonary fibrosis,and its mechanism may be related to the regulation of TGF-β1/Smad signaling pathway.