多西环素减轻小鼠内毒素性急性肺损伤的作用及机制研究

目的：探讨多西环素对内毒素性急性肺损伤的影响及机制。方法：将昆明小鼠随机分为：生理盐水对照组、多西环素组、内毒素脂多糖（LPS）急性肺损伤模型组及多西环素干预组。注射LPS24h后处死动物,行支气管肺泡灌洗（BALF）,计数灌洗液中白细胞数量及测定总蛋白含量。用ELISA分别测定肺组织匀浆上清液中TNF-a、基质金属蛋白酶-9（MMP-9）和金属蛋白酶组织抑制剂-1（TIMP-1）的含量。同时取肺组织进行病理学观察,测定肺组织湿/干重比值。结果：多西环素显著减少LPS所致BALF中白细胞数量、总蛋白浓度和肺组织湿/干重比值（P〈0.01）。多西环素能降低肺组织匀浆上清液中TNF-a和MMP-9含量（P〈0.01）,轻度上调TIMP-1的含量。多西环素能显著减轻LPS所致肺组织出血、肺水肿及炎性细胞浸润等肺损伤改变。结论：多西环素可减轻LPS所致急性肺损伤,其机制可能与抑制TNF-α等促炎因子释放及下调MMP-9/TIMP-1比值有关。

Protection effect and mechanism of Doxycycline on lipopolysaccharide induced acute lung in mice

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(BAIJF)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 bv EUSA.RESULTS:LPS-induced increases in total protein concentration.WBC number in BALF and W/Dlevels 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-α and 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).