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作 者:刘杨 罗振亮 严福林 潘春 吕冰清 唐阿梅 杨长福 LIU Yang;LUO Zhen-liang;YAN Fu-lin;PAN Chun;LV Bing-qing;TANG A-mei;YANG Chang-fu(Basic Medical School,Guiyang University of Traditional Chinese Medicine,Guiyang 550025,China;College of Pharmacy,Guiyang University of Traditional Chinese Medicine,Guiyang 550025,China;Respiratory department of Guizhou Province Hospital of Traditional Chinese Medicine,Guiyang University of Traditional Chinese Medicine,Guiyang 550025,China)
机构地区:[1]贵州中医药大学基础医学院,贵州贵阳550025 [2]贵州中医药大学药学院,贵州贵阳550025 [3]贵州中医药大学第一附属医院呼吸科,贵州贵阳550025
出 处:《中草药》2020年第16期4244-4250,共7页Chinese Traditional and Herbal Drugs
基 金:国家自然科学基金资助项目(81660735);贵州省教育厅资助项目(黔教合KY字[2016]189);贵州省科技厅联合基金(黔科合LH字[2016]7503)。
摘 要:目的观察桑根酮C对博莱霉素诱导的小鼠肺纤维化的影响,并探讨其可能的作用机制。方法 C57BL/6小鼠随机分为4组,即假手术组、模型组和桑根酮C(100、50 mg/kg)组,每组20只。假手术组小鼠气管内注射生理盐水,模型组小鼠气管内注射博莱霉素诱导肺纤维化模型。术后第4天开始给药,连续给药28d后检测小鼠呼吸功能;检测肺内羟脯氨酸含量;HE染色观察肺内炎症表现;Masson染色观察肺内胶原活性;免疫组化法检测肺内转化生长因子-β1(TGF-β1)蛋白表达量;免疫蛋白印迹法检测肺内α平滑肌肌动蛋白(α-SMA)、核转录因子-κB p65(NF-κB p65)、磷酸化的核转录因子-κB p65(p-NF-κB p65)、Ⅰ型胶原和Ⅲ型胶原表达量。结果与模型组比较,桑根酮C能够改善经博莱霉素诱导形成肺纤维化后小鼠的呼吸功能,能够明显降低肺内羟脯氨酸含量,明显减轻肺内炎症和胶原沉积,肺内TGF-β1、α-SMA、NF-κBp65、p-NF-κBp65、Ⅰ型胶原和Ⅲ型胶原蛋白表达量明显降低。结论桑根酮C能够明显改善博莱霉素诱导小鼠肺纤维化,改善呼吸功能,其机制可能与抑制TGF-β1过表达和降低炎症转录因子NF-κB及磷酸化表达有关。Objective To observe the effect of sanggenon C on pulmonary fibrosis induced by bleomycin and explore its possible mechanism. Methods C57BL/6 mice were randomly divided into four groups: control group, model group, sanggenon C(100 and 50 mg/kg) group, 20 mice for each group. The control group and model group were induced by intratracheal injection of saline and bleomycin, respectively. The administration was started on day 4 after the operation, and the respiratory function of the mice was detected after 28 d of continuous administration. The content of hydroxyproline in lung was measured. Pulmonary inflammation and activity of collagen in lung were observed by HE staining and Masson staining. The expression of TGF-β1 protein in lung was detected by immunohistochemistry and detection of the expression of α-SMA, NF-κBp65, p-NF-κBp65, type Ⅰ collagen and type Ⅲ collagen in lung was detected by Western-blotting. Results Compared with model group, sanggenon C improved the respiratory function in mice with pulmonary fibrosis induced by bleomycin. It significantly decreased the content of hydroxyproline, alleviated the degree of inflammation, and reduced the deposition of collagen in lung. The expression of TGF-β1, α-SMA, NF-κBp65, p-NF-κBp65, type Ⅰ collagen and type Ⅲ collagen in lung was significantly reduced. Conclusion Sanggenon C can significantly improve the pulmonary fibrosis and respiratory function induced by bleomycin in mice. The mechanism may be related to the inhibition of TGF-β1 overexpression and the decrease of the expression of inflammatory transcription factor NF-κB and phosphorylation.
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