C3aR拮抗剂治疗PR8/MRSA共感染小鼠肺炎损伤的研究

C3aR antagonist against pneumonia injury in mice co-infected with PR8/MRSA

目的补体异常激活可大量产生过敏毒素C3a分子,通过利用C3aR受体拮抗剂(C3aRa)可抑制C3a功能,达到治疗流感病毒和金黄色葡萄球菌(PR8/MRSA)共感染小鼠肺炎损伤的目的,探究一种治疗共感染重症肺炎损伤的新策略。方法PR8/MRSA共感染小鼠尾静脉注射C3aR受体拮抗剂C3aRa,剂量1 mg/kg,1次/2 d,观察记录小鼠死亡率变化;测量共感染小鼠体质量,取新鲜肺组织称重,计算肺指数;制备小鼠肺组织石蜡切片并行HE染色,观察肺部病理改变。结果经过敏毒素受体拮抗剂C3aRa干预后的共感染小鼠较对照组生存率提高了30%,肺组织充血、水肿和出血程度减轻,肺指数明显下降(P<0.001)。结论C3aRa在流感/细菌共感染重症肺炎的治疗中具有一定疗效,为临床利用补体干预治疗共感染重症肺炎提供了一种新策略。

Objective To explore a new strategy against severe co-infected pneumonia injury by inhibiting the function of C3 a. Methods C3 aR receptor antagonist C3 aRa was injected into the tail vein of mice co-infected with PR8/MRSA at a dose of 1 mg/kg once every 2 d. The mortality of mice was observed and recorded. The body mass of co-infected mice was measured,fresh lung tissue was taken and weighed,and the lung index was calculated. Paraffin sections of mouse lung tissue were prepared and HE staining was performed to observe the pathological changes in the lungs. Results Compared with the control group,the survival rate of co-infected mice treated with anaphylotoxin receptor antagonist C3 aRa was improved by 30%. The degree of pulmonary hyperemia,edema and bleeding were reduced,and the pulmonary index was significantly decreased(P<0.001). Conclusion C3 aR receptor antagonist(C3 aRa)has therapeutic effect against influenza/bacterial co-infected severe pneumonia,which provides a new strategy for the clinical use of complement intervention in the treatment of co-infected severe pneumonia.