摘要
目的探讨五味子提取物对百草枯(PQ)中毒模型小鼠肺纤维化的保护作用,并探讨其机制。方法 108只小鼠按随机数字表法分为正常对照组,模型组,五味子提取物低剂量组(200 mg/kg)、中剂量组(400 mg/kg)、高剂量组(800 mg/kg)及维生素C组(100 mg/kg),每组18只。除正常对照组以外的小鼠行一次性PQ溶液(100 mg/kg)灌胃造模,造模成功后每24 h给予相应剂量药物1次,分别在建模后第7、14、21天处死小鼠,每个时间点6只。解剖肺脏,HE染色观察小鼠肺组织炎症程度并进行炎症评分;Masson染色观察肺组织纤维化程度;RT-PCR和酶联免疫吸附试验(ELISA)分别检测各组肺组织中转化生长因子(TGF)-β1、白细胞介素(IL)-6、IL-17 m RNA及蛋白表达水平。结果 (1)造模后第7天和第14天,模型组小鼠肺组织出现大量炎性细胞浸润、肺泡间隔充血,炎症评分较正常对照组升高(P<0.05),而五味子提取物中、高剂量组小鼠肺组织炎症评分较模型组和维生素C组降低(P<0.05)。(2)造模后第14天和第21天,五味子中、高剂量组小鼠肺组织纤维化程度较模型组降低(P<0.05)。(3)随着造模时间的延长,模型组TGF-β1 m RNA及蛋白表达水平升高,IL-6表达降低,IL-17则先升高后降低。五味子提取物中、高剂量组与模型组比较,造模后第7天和第14天,IL-6表达降低,造模后第14天和第21天,TGF-β1表达降低,而3个时间点IL-17表达均降低(P<0.05)。结论五味子提取物可通过抑制TGF-β1、IL-6和IL-17的表达来减轻PQ中毒造成的炎症反应和肺纤维化。
Objective To explore the protective effcets of Schisandra chinensis extract （SCE） in paraquat （PQ）-induced pulmonary fibrosis in mice ,and its intrinsic molecular mechanisms thereof. Methods A total of 108 mice were randomly allocated into six groups （n=18）：control group, model group, low concentration of SCE group （200 mg/kg）, medium concentration of SCE group （400 mg/kg）, high concentration of SCE group （800 mg/kg） and vitamin C group （100 mg/kg）. Except control group, mice were given by intragastric administration with PQ （100 mg/kg） and administered with SCE and Vitamin C once per 24 h after PQ modeling. Mice were sacrificed at 7, 14 and 21 d after modeling. Six mice were executed at different time points. The degree of lung tissue inflammation and fibrosis were observed by HE staining and Masson staining. The mRNA and protein expression levels of transforming growth （TGF）-β1, interleukin （IL）-6 and IL-17 in lung tissue were determined by RT-PCR and ELISA respectively. Results （1） Compared with control group, the lung tissue of model group showed a large number of inflammatory cell infiltration, space congestion, and its inflammation scores increased at 7 and 14 days after modeling （P〈0.05）. At the same time, compared with model group and vitamin C group, inflammation scores were significantly decreased in medium concentration of SCE group and high concentration of SCE group （P〈0.05）. （2） Compared with control group, collagen fibers and the degree of fibrosis were significantly increased in model group ,while pulmonary fibrosis were decreased in medium concentration of SCE group and high concentration of SCE group at 14 and 21 days after modeling （P〈0.05）. （3） With the extension of modeling time, both mRNA and protein expressions of TGF-β1 were obviously elevated, IL-6 decreased and IL-17 reduced after the first increase in PQ group. Compared with PQ group, levels of three cytokines mRNA and protein expression in medium concentration of SCE group and high concentration of SCE group changed as follows：IL-6 level was markedly decreased at 7 and 14 days after modeling;TGF-β1 level was markedly increased at 14 and 21 days after modeling. However, IL-17 level was markedly decrease at three time points（P〈0.05）. Conclusion SCE can relieve PQ-induced lung inflammation and fibrosis by suppressing TGF-β1, IL-6, and IL-17 expressions.
出处
《天津医药》
CAS
2016年第5期589-593,I0005,共6页
Tianjin Medical Journal
基金
天津市应用基础与前沿技术研究计划青年项目(14JCQNJC10300)
武警后勤学院院级科学基金(WHM201308)
