大麻二酚对博来霉素诱导肺纤维化大鼠的药效学研究  

Pharmacodynamic study of cannabidiol on bleomycin⁃induced pulmonary fibrosis in rats

作　　者：孙梦迪 张飞宇[1] 高鑫[1] 王宇[2] 陈平平[2] 刘树民[2] SUN Meng-di;ZHANG Fei-yu;GAO Xin;WANG Yu;CHEN Ping-ping;LIU Shu-min(Heilongjiang University of Traditional Chinese Medicine,Harbin 150040,China;Institute of Traditional Chinese Medicine,Heilongjiang University of Traditional Chinese Medicine,Harbin 150040,China)

机构地区：[1]黑龙江中医药大学,黑龙江哈尔滨150040 [2]黑龙江中医药大学中医药研究院,黑龙江哈尔滨150040

出　　处：《海南医学院学报》2023年第22期1681-1688,1695,共9页Journal of Hainan Medical University

基　　金：黑龙江省博士后面上项目(LBH-Z22251);黑龙江省中医药科研课题项目(ZHY2022-114);黑龙江省中医药学会青年人才托举工程项目(2022-QNRC1-27)。

摘　　要：目的:研究大麻二酚(CBD)对肺纤维化大鼠的保护作用,并探讨其可能的机制,为CBD治疗肺纤维化提供理论依据。方法:将60只SD大鼠随机分为正常对照组、模型组、泼尼松组、CBD低、中、高剂量组(12、36、108 mg/kg,ig),每组10只,除正常对照组外,其余5组均使用气管注射博来霉素的方法构建肺纤维化大鼠模型,造模后开始每天1次灌胃给药,连续灌胃28 d,采集样本。检测肺水肿程度;HE、Masson染色法观察肺组织病理改变;ELISA法测定肿瘤坏死因子α(TNF-α),白细胞介素-1β(IL-1β),白细胞介素-6(IL-6)含量及肺组织超氧化物歧化酶(SOD)、丙二醛(MDA)、羟脯氨酸(HYP)含量,免疫组化法检测转化生长因子-β1(TGF-β1)、α-平滑肌肌动蛋白(α-SMA)的浓度,实时荧光定量PCR(qRT-PCR)法检测TGF-β1,α-SMA,Nrf2和核转录因子-κB p65(NF-κB p65)的mRNA表达水平。结果:CBD给药组肺脏器系数和W/D值显著降低(P<0.05);中、高剂量的CBD能减少胶原纤维数量和成纤维细胞;CBD低、中、高剂量组肺纤维化大鼠血清中TNF-α,IL-1β,IL-6和肺组织中MDA、HYP的含量均较模型组明显减少,SOD水平明显升高(P<0.05);大鼠肺组织中TGF-β、α-SMA的表达均较模型组减少(P<0.05);肺组织中TGF-β1、α-SMA、NF-κB p65 m RNA含量降低,Nrf2 mRNA的表达水平升高(P<0.05),尤以高剂量组疗效最为显著。结论:CBD可显著减轻大鼠肺纤维化程度,其潜在机制可能与抑制炎症反应,增强抗氧化能力和抑制TGF-β1和α-SMA的蛋白表达有关。Objective:To study the protective effect of cannabidiol(CBD)on rats with pulmonary fibrosis and explore the possible mechanism of the use of CBD in the treatment of pulmonary fibrosis.Methods:Sixty SD rats were randomly divided into the normal control group,model group,prednisone group,CBD low,medium and high dose groups(12,36,108 mg/kg,ig),10 rats in each group.Except for the normal control group,the other 5 groups were all induced by tracheal injection of bleomycin to rat models of pulmonary fibrosis.After modeling,the rats were given intragastric administration once a day for 28 consecutive days and samples were taken.The degree of pulmonary edema was detected;the pathological changes of lung tissue were ob-served by HE and Masson staining;tumor necrosis factorα(TNF-α),interleukin-1β(IL-1β),interleukin-6(IL-6)and lung tis-sue superoxide dismutase(SOD),malondialdehyde(MDA),hydroxyproline(HYP)contents were measured by ELISA,trans-forming growth factor-β1(TGF-β1)andα-smooth muscle protein(α-SMA)concentration were detected by immunocytochemical method,real-time fluorescent quantitative PCR(qRT-PCR)method was used to detect the mRNA expression levels of TGF-β1,α-SMA,Nrf2 and nuclear transcription factor-κB p65(NF-κB p65).Results:The lung organ coefficient and W/D value were sig-nificantly decreased in the CBD administration group(P<0.05);medium and high doses of CBD could reduce the number of col-lagen fibers and fibroblasts;the pulmonary fibrosis in the low,medium,and high dose groups of CBD was significantly lower.The levels of TNF-α,IL-1β,and IL-6 in rat serum,as well as MDA and HYP in lung tissue,were significantly lower compared to the model group.Additionally,the level of SOD was significantly increased(P<0.05);The expression ofα-SMA was de-creased compared with the model group(P<0.05);the contents of TGF-β1,α-SMA and NF-κB p65 mRNA in lung tissue de-creased,and the expression level of Nrf2 mRNA increased(P<0.05).Especially,the high-dose group had the most significant ef-fect.Conclusion:CBD

关 键 词：大麻二酚 肺纤维化 炎症 氧化应激 药效学 

分 类 号：R285.5[医药卫生—中药学]