关键词: 多西环素, 急性肺损伤, 基质金属蛋白酶-9, 金属蛋白酶组织抑制剂-1, 脂多糖

Abstract: AIM: To investigate the potential role and of Doxycycline in lipopolysaccharide-induced acute lung injury in mice and its possible mechanism. METHODS: Kunming mice were treated with Doxycycline (20 mg/kg)or saline an hour before LPS administration (10 mg/kg)by intraperitoneal injection and were decapitated 24 h after LPS challenge.The bronchoalveolar lavage fluid (BALF)samples were analyzed for total protein concentrateion and white blood cell (WBC)count.The lung samples were taken for histopathological evaluation and for determination of lung wet-to-dry weight ratio (W D).The changes of tumor necrosis factor α(TNF-α), matrix metalloproteinase-9 (MMP-9), tissue inhibitor of metalloproteinase-1 (TIMP-1)levels in the pulmonary tissues were detected by ELISA. RESULTS: LPS-induced increases in total protein concentration, WBC number in BALF and W D levels of lung tissues, were significantly attenuated in Doxycycline-treated mice (P <0.01).Doxycycline treatment also resulted in a significant protection of lung tissues against LPS-induced acute lung injury via decreasing TNF-αand MMP-9(P <0.01).However, TIMP-1 levels were slightly higher in Doxycycline-treated group than those in LPS group.Histological examination revealed that doxycycline treatment resulted in reduced hemorrhage, intra-alveolar edema and neutrophilic infiltration. CONCLUSION: It suggest that Doxycycline plays a protective role in attenuating LPSinduced acute lung injury in mice, which may be the mechanism through regulating the balance of MMP-9 TIMP-1 and inhibiting the pro-inflammatory factor (TNF-α).

Key words: Doxycycline, acute lung injury, matrix metalloproteinase-9, tissue inhibitor of metalloproteinase-1, lipopolysaccharide