重组活化基因1缺陷鼠和正常小鼠急性细菌性鼻窦炎模型的比较研究

目的　探讨C5 7BL/ 6J 重组活化基因 1(recombinantactivegene 1,Rag1)敲除鼠 (简称Rag1小鼠 )和C5 7BL/ 6 (C5 7)小鼠急性细菌性鼻窦炎的自然感染过程及二者之间的差别。方法　Rag1缺乏鼠和C5 7小鼠各 10只 ,采用鼻孔内接种肺炎链球菌T5 9,另外 4只接种大豆肉汤作对照。分别于接种2d(各 2只 )、5d(各 4只 )、10d(各 2只 )、14d(各 2只 )处死动物 ,对照组于第 5天处死。处死前作鼻腔灌洗培养 ,头颅石蜡包埋 ,连续切片 ,Luna染色 ,计算机辅助光镜观察 ,计算窦腔内中性粒细胞集落所占窦腔的百分率和每平方毫米窦腔黏膜中浸润的多形核白细胞数。结果　接种 5dRag1小鼠和C5 7小鼠窦腔感染均达到高峰 ,窦腔中白细胞集落和黏膜中白细胞数均明显高于对照组 (P <0 0 5 ) ,10d后C5 7小鼠窦腔感染逐渐减轻 ,14d后基本控制 ,而Rag1小鼠感染持续存在 ,与C5 7比较差异有显著性(P <0 0 5 ) ,14d后鼻灌洗液中仍培养出肺炎链球菌。结论　采用肺炎链球菌T5 9鼻内接种法成功地诱导出Rag1和C5 72种小鼠急性鼻窦炎 ,肺炎链球菌在C5 7小鼠鼻腔鼻窦内的感染可被完全、自主、快速控制 ,但Rag1小鼠则不能完全控制这种感染 ,并有演变成慢性炎症的倾向 ,提示T和B淋巴细胞依赖性免疫功能在清除细菌感染中起着关键的作用 ,基因敲除

A comparative experimental study between recombinant active gene 1-deficient mice and C57BL/6 mice model of acute bacterial rhinosinusitis

Objective To explore the infective course of acute bacterial rhinosinusitis in recombinent active gene 1 (Rag 1)-defecient mice (Rag1) and C57BL/6 mice (C57) and the difference between them after intranasal streptococcus pneumoniae inoculation. Methods Ten mice of each strain (Rag1 and C57) received Streptococcus pneumoniae strain T59, ATCC 49 619 suspended in trypticase soy broth, and controls (two mice for each strain) received trypticase soy broth alone. After 2, 5, 10 and 14 days, nasal lavage cultures were obtained and then the mice were killed. The heads were embedded with paraffin and serial sections were made for histological analysis. The percentage of sinus cavity occupied by neutrophil cluster (% cluster) and the number of polymorphonuclear leukocytes per square millimeter of sinus mucosa (PMN/mm 2) were calculated by the use of a computer-aided microscope in conjunction with a reconstruction and image analysis system. Results % Cluster and PMN/mm 2 in infected mice both of Rag1 and C57 appeared to peak on five and ten days separately, which were significantly heavier than those in controls(P<0.05). The infection in C57 decreased by two weeks. But in contrast to C57, the infection in Rag1 had not been controlled and Streptococcus pneumoniae were still seen in the nasal lavage culture by two weeks. This difference between infected Rag1 and infected C57 was significant at P<0.05. Conclusion Acute bacterial rhinosinusitis in Rag1 and C57 mice were successfully induced by intranasal inoculation of streptococcus pneunoniae. This bacterial infection in C57 could be controlled completely and rapidly. In contrast, Rag1 failed to control rhinosinusitis and had a tendency to chronic inflammation, suggesting that T- and B-cell-dependent immunity was important for clearance of bacteria from rhinosinus and gene knockout mice was a convenient tool for investigation of the pathogenesis of experimental rhinosinusitis.