目的 研究芹菜素對百草枯致小鼠肺纖維化的保護作用及機制。方法 將小鼠隨機分為對照組、模型組、地塞米松組（1 mg/kg）和芹菜素低、高劑量（10、20 mg/kg）組，除對照組外，其他各組ip百草枯（50 mg/kg）建立小鼠肺纖維化模型，第8天開始ig給藥，連續(xù)給藥21 d。觀察小鼠體質(zhì)量變化；測量小鼠肺系數(shù)；采用HE染色觀察肺組織形態(tài)學變化；免疫組化法觀察小鼠肺組織中Ⅰ、Ⅲ型膠原表達變化；ELISA法檢測各組小鼠肺組織中Ⅰ、Ⅲ型膠原和炎癥因子腫瘤壞死因子（TNF）-α、白細胞介素（IL）-6、IL-1β含量；Western blotting法測定肺組織Caveolin-1蛋白表達水平。結(jié)果 造模第28天時，與模型組比較，芹菜素低、高劑量組小鼠體質(zhì)量顯著增加（P<0.05）；地塞米松組和芹菜素低、高劑量組肺系數(shù)顯著降低（P<0.05）；芹菜素低、高劑量組肺組織內(nèi)炎性細胞浸潤較少、肺泡壁斷裂及肺泡腔融合較少，肺纖維化程度較輕；芹菜素低、高劑量組和地塞米松組小鼠的肺組織中Ⅰ、Ⅲ型膠原和IL-6、IL-1β、TNF-α含量顯著下降（P<0.01），Caveolin-1蛋白表達顯著下降（P<0.01）。結(jié)論 芹菜素對百草枯誘導小鼠肺纖維化具有保護作用，其機制可能與Ⅰ、Ⅲ型膠原含量及炎癥因子水平下調(diào)、Caveolin-1蛋白表達水平下調(diào)相關(guān)。

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

江蘇省無錫市衛(wèi)生健康委員會醫(yī)學科研項目（MS201658）