目的 研究芹菜素对百草枯致小鼠肺纤维化的保护作用及机制。方法 将小鼠随机分为对照组、模型组、地塞米松组（1 mg/kg）和芹菜素低、高剂量（10、20 mg/kg）组，除对照组外，其他各组ip百草枯（50 mg/kg）建立小鼠肺纤维化模型，第8天开始ig给药，连续给药21 d。观察小鼠体质量变化；测量小鼠肺系数；采用HE染色观察肺组织形态学变化；免疫组化法观察小鼠肺组织中Ⅰ、Ⅲ型胶原表达变化；ELISA法检测各组小鼠肺组织中Ⅰ、Ⅲ型胶原和炎症因子肿瘤坏死因子（TNF）-α、白细胞介素（IL）-6、IL-1β含量；Western blotting法测定肺组织Caveolin-1蛋白表达水平。结果 造模第28天时，与模型组比较，芹菜素低、高剂量组小鼠体质量显著增加（P<0.05）；地塞米松组和芹菜素低、高剂量组肺系数显著降低（P<0.05）；芹菜素低、高剂量组肺组织内炎性细胞浸润较少、肺泡壁断裂及肺泡腔融合较少，肺纤维化程度较轻；芹菜素低、高剂量组和地塞米松组小鼠的肺组织中Ⅰ、Ⅲ型胶原和IL-6、IL-1β、TNF-α含量显著下降（P<0.01），Caveolin-1蛋白表达显著下降（P<0.01）。结论 芹菜素对百草枯诱导小鼠肺纤维化具有保护作用，其机制可能与Ⅰ、Ⅲ型胶原含量及炎症因子水平下调、Caveolin-1蛋白表达水平下调相关。

Objective To investigate the protective effect of apigenin on paraquat-induced pulmonary fibrosis in mice. Methods Mice were randomly divided into control group, model group, dexamethasone (Dex) group (1 mg/kg), apigenin low and high dose group (10 and 20 mg/kg). Except the control group, mice in the other groups were treated with paraquat (50 mg/kg, ip) to induce pulmonary fibrosis in mice. The drug was administrated for 21 consecutive days 7 days later. The body weight of mice was observed. The lung coefficient was measured. The morphological changes of lung tissue were observed by HE staining. The levels of proinflammatory cytokines including interleukin-6 (IL-6), interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α) were measured by enzyme-linked immunosorbent assay (ELISA). The protein expression level of Caveolin-1 was detected by Western blotting. Resluts On the 28th day, compared with model group, the weight of mice in the low and high dose apigenin groups increased significantly (P < 0.05). The lung coefficient of dexamethasone group and apigenin low and high-dose groups decreased significantly (P < 0.05). In the low and high dose apigenin groups, the infiltration of inflammatory cells in lung tissue was less, the rupture of alveolar wall and the fusion of alveolar cavity were less, and the degree of pulmonary fibrosis was less. The expression of type I and III collagen, IL-6 and IL-1β, TNF-α in lung tissue and the protein expression of caveolin-1 of mice in apigenin low, highdose group and dexamethasone group decreased significantly (P < 0.01). Conclusion Apigenin exhibits protective effect on paraquatinduced pulmonary fibrosis in mice which may relate to the down-regulation of type I and type III collagen content, inflammatory cytokines levels and Caveolin-1 protein expression.

R285.5

江苏省无锡市卫生健康委员会医学科研项目（MS201658）