替加环素在腹腔感染致脓毒症肺损伤中的作用研究

The Effect of Tigecycline on The Gut Derived Infection Induced Lung Injury in Sepsis Mice

目的:探讨替加环素(TIG)在腹腔感染致肺损伤中的治疗效果。方法:应用盲肠结扎穿孔(CLP)的方法构建重症脓毒症模型,48只BALB/c小鼠随机分为4组,假手术组(sham)组、CLP+生理盐水组(CLP+NS)组、CLP+美罗培南组(CLP+MEPM)组、CLP+替加环素组(CLP+TIG)组。造模3 h后腹腔注射给药,TIG按6.25mg/kg给药,美罗培南(MEPM)按50 mg/kg给药。给药6 h后检测肺湿/干重、进行肺脏组织病理学检测、血及肺组织细菌培养。结果:组织病理学结果显示,sham组中肺泡结构正常,CLP+NS组中可见肺间质大量炎性细胞浸润,给予MEPM和TIG治疗后,肺间质内炎性细胞浸润程度明显减少;与CLP+MEPM组相比,CLP+TIG组组织损伤较轻,组织损伤评分下降。细菌培养结果显示:CLP+NS组中小鼠全血、肺组织细菌数均明显升高,CLP+MEPM组和CLP+TIG组中全血、肺组织中CFU均较CLP+NS组下降,以CLP+TIG组更明显,各组间差异明显(P均<0.05)。肺干/湿重结果显示:与sham组相比,CLP+NS组中肺水含量明显上升,湿重/干重明显升高,CLP+MEPM组和CLP+TIG组中肺水、湿重/干重较生理盐水组下降,以CLP+TIG组更明显,各组间差异明显(P均<0.05)。结论:TIG治疗可有效改善肠源性脓毒症肺损伤的情况。

Objective：To explore the tigecycline（TIG）on the lung injury induced by abdominal infection. Methods：A sepsis mice model were established by cecal ligature and puncture（CLP）. 48 BALB/c mice were randomly di-vided into four groups：sham group,CLP ＋ normal saline group（CLP＋NS）,CLP ＋ meropenem group（CLP＋MEPM）,CLP ＋ tigecycline group（CLP＋TIG）. The mice in received the drug（TIG 6.25 mg/kg and MEPM 50 mg/kg）3 h afterCLP. The wet/dry lung weight ratio（W/D）,pathologic changes,the bacteria culture of blood and lung tissue were mea-sured 6 h after the drug treatment. Results：There was no obvious histopathological damage in the sham group,while se-vere inflammatory infiltration could be seen in the CLP ＋NS group. After the treatment of MEPM and TIG,the inflamma-tory infiltration was decreased. Compared with the CLP＋MEPM group,the lung tissue showed less severe. The bacteriaculture results showed that the colony forming units（CFU）were increased significantly in CLP mice. The CFU were de-creased after MEPM and TIG treatment,and TIG showed a better effect. Difference was statistically significant（all P0.05）. The levels of W/D were increased in CLP＋NS group. Compared with the CLP＋NS group,the ratios were de-creased in CLP＋MEPM group and CLP＋TIG group. Difference was statistically significant（all P0.05）. Conclusion：Ti-gecyline treatment may be beneficial to the lung injury induced by abdominal infection.