N-乙酰半胱氨酸对大鼠肺炎链球菌肺炎的保护性研究

Protective effect of N-acetylcysteine on streptococcus pneumonia model of rats

目的探讨N-乙酰半胱氨酸(NAC)对肺炎链球菌感染大鼠所致肺炎是否有保护作用。方法本实验采用国际通用方法制造肺炎链球菌肺部感染模型。用清洁级Wistar大鼠24只,随机分为3组,每组8只,A组(未灌NAC注菌组)、B组(灌NAC注菌组)、C组(未灌药未注菌组)。从实验第1天开始A组给予NAC药物灌胃,B组以等量无菌注射用水灌胃。第4天A、B组通过气管注入0.4ml肺炎链球菌稀释液,对照组通过气管注入0.4ml无菌生理盐水,每组仅注入1次;第7天后处死取材,测定中性粒细胞表面CD11b/c、中性粒细胞活性氧浓度(ROS),白介素-10(IL-10)、白介素-6(IL-6)含量。病理切片,观察肺组织结构变化。结果 A组显微镜下明显可见肺泡大小不一致,肺泡间隔增宽增厚,间质内大量中性粒细胞、淋巴细胞浸润。B组也可见上述病理变化,但较A组减轻,C组肺泡大小较一致,肺泡间隔无明显增宽增厚,间质内极少量中性粒细胞及淋巴细胞浸润。AB两组间中性粒细胞CD11b/c比较差异具有统计学意义(F=53.65,P<0.01);两组间中性粒细胞活性氧(ROS)比较差异具有统计学意义(F=63.97,P<0.01);两组间IL-10比较差异具有统计学意义(F=74.66,P<0.01);两组间IL-6比较差异具有统计学意义(F=238.59,P<0.01),以上指标均B组较A组值低。结论 N-乙酰半胱氨酸能够减轻大鼠肺炎链球菌肺炎的炎症反应和肺组织破坏,其抗氧化作用对肺炎链球菌所致肺炎可能有一定保护作用。

Objective To explore the protective effect of N-acetylcysteine（ NAC） for pneumonia caused by infection of streptococcus pneumoniae in rats. Methods This study used internationally accepted method of producing animal model that infected by streptococcus pneumoniae. 24 healthy clean male Wistar rats were randomly divided into 3 groups： the group A（ infection and no NAC group）,the group B（ NAC and infection group）,the group C（ no infection and no NAC group）. NAC（ 300 mg/（ kg·d）） were fed by intragastric administration on the first day,while the same amount of distilled water was fed in the control group. The rats were intratracheally instilled with 0.4ml suspension of streptococcus pneumoniae on the fourth day. At the same time,the no-infection groups were intratracheally instilled with 0. 4 ml sterile saline. At the end of experiment,the rats were killed. The leukocytes and neutrophils,CD11 b and DCFH-DA in the blood were analyzed. Results In the group A,alveolus showed different sizes,alveolar septum became wide and thick,and large number of neutrophils and lymphocytes infiltrated in the interstitial. Some changes like these could be find in the group B,but less severe than the group A. A few of the same changes but less severe could be observed in the group C. Compared with the group A and the group B,there was a statistically significant difference in the mean value of CD11 b / c（ F = 53. 65,P〈 0.01）. The same trend was observed in ROS（ F = 63. 97,P〈 0.01）,IL-10（ F = 74. 66,P〈 0.01） and IL-6（ F = 238. 59,P〈 0.01）. The above indicators were lower in the group B than in the group A. Conclusion NAC could alleviate inflammatory response these changes. The antioxidation effect of NAC may play a role in protection of lung infection. N-acetylcysteine can reduce inflammation and lung tissue damage of rats by infection of pneumococcal pneumonia. Its antioxidant effect may have a protective effect in pneumonia caused by Streptococcus pneumoniae.