CAJ | 학술논문

目的探讨中国恒河猴结核病模型的建立方法,并对中国恒河猴作为结核病动物模型做出评价.方法应用简单随机分组法将12只中国恒河猴分为注入低菌量组(20 CFU)、注入高菌量组(100 CFU)和滴注高菌量组(100 CFU),每组4只,雌雄各半.将MTB分别通过支气管镜和气管内滴注法感染猴,动态观察恒河猴的临床表现,定期进行ESR、C反应蛋白、PPD试验和X线胸片检查,感染后24周行病理检查.采用方差分析进行多组间比较.结果 3组感染MTB的恒河猴均出现不同程度的体温升高、体重下降、食欲下降和咳嗽等症状,体温于感染后8周达到高峰[(40.1±0.2)℃],感染后24周体重下降明显[(-5.5±5.6)％],感染后6-8周ESR明显升高[(36±40) mm/1 h],感染后6～ 24周C反应蛋白明显升高[(75.8 ±49.8)mg/L],旧结核菌素试验均为阳性.注入低菌量组动物的病变进展缓慢,X线胸片以斑片影为主,注入高菌量组和滴注高菌量组动物的病变发展迅速,4～12周以斑片影和结节影为主,12 ～ 24周以片状影和实变影多见.肺组织、纵隔淋巴结、肾脏和脾脏可见与人结核病相似的结核性肉芽肿及于酪样坏死,抗酸染色均为阳性,病理改变严重程度为注入高菌量组＞滴注高菌量组＞注入低菌量组,注入高菌量组右肺细菌载量[(6.7±1.0) lg CFU/g]高于注入低菌量组和滴注高菌量组[(5.9±1.3)lgCFU/g和(5.8 ±2.0)lg CFU/g],3组间比较,差异无统计学意义(F=0.97,P＞0.05).结论中国恒河猴经支气管镜和气管内滴注MTB均可成功建立非人灵长类动物结核病模型,其临床表现、疾病进展及病理改变与人原发性结核病和血行播散性结核病相似.
목적 탐토중국항하후결핵병모형적건립방법,병대중국항하후작위결핵병동물모형주출평개.방법 응용간단수궤분조법장12지중국항하후분위주입저균량조(20 CFU)、주입고균량조(100 CFU)화적주고균량조(100 CFU),매조4지,자웅각반.장MTB분별통과지기관경화기관내적주법감염후,동태관찰항하후적림상표현,정기진행ESR、C반응단백、PPD시험화X선흉편검사,감염후24주행병리검사.채용방차분석진행다조간비교.결과 3조감염MTB적항하후균출현불동정도적체온승고、체중하강、식욕하강화해수등증상,체온우감염후8주체도고봉[(40.1±0.2)℃],감염후24주체중하강명현[(-5.5±5.6)％],감염후6-8주ESR명현승고[(36±40) mm/1 h],감염후6～ 24주C반응단백명현승고[(75.8 ±49.8)mg/L],구결핵균소시험균위양성.주입저균량조동물적병변진전완만,X선흉편이반편영위주,주입고균량조화적주고균량조동물적병변발전신속,4～12주이반편영화결절영위주,12 ～ 24주이편상영화실변영다견.폐조직、종격림파결、신장화비장가견여인결핵병상사적결핵성육아종급우락양배사,항산염색균위양성,병리개변엄중정도위주입고균량조＞적주고균량조＞주입저균량조,주입고균량조우폐세균재량[(6.7±1.0) lg CFU/g]고우주입저균량조화적주고균량조[(5.9±1.3)lgCFU/g화(5.8 ±2.0)lg CFU/g],3조간비교,차이무통계학의의(F=0.97,P＞0.05).결론 중국항하후경지기관경화기관내적주MTB균가성공건립비인령장류동물결핵병모형,기림상표현、질병진전급병리개변여인원발성결핵병화혈행파산성결핵병상사.
Objective To establish and evaluate the Chinese rhesus model of tuberculosis.Methods Twelve Chinese rhesus macaques,randomly divided into 3 groups,were inoculated with 2 different doses of Mycobacterium tuberculosis H37Rv strain via both bronchoscopic and intratracheal instillation into the lungs.Clinical observation and laboratory examinations were performed,including erythrocyte sedimentation rate,C-reactive protein,tuberculin skin test and X-ray examination.Histopathological assessments were performed in the 24th week postinfection.Statistical analysis was performed by ANOVA in the 3 groups.Results After infection all the animals manifested fever,weight lose,lack of appetite,coughing and other symptoms of tuberculosis.The temperature gradually increased and reached a peak [(40.1 ±0.2) ℃] at the 8th week postinfection.The weight decreased significantly at 24th week postinfection (-5.5 ± 5.6) ％.Erythrocyte sedimentation rate elevated significantly at the 6th to 8th week postinfection (36 ±40) mm/1 h.C-reactive protein was significantly increased at the 6th to 24th week after infection (75.8 ± 49.8) mg/L.The positive rate of tuberculin skin test was 100％.In Group Ⅰ (bronchoscopic instillation,20 CFU) the disease developed slowly,and the main manifestation of chest X-ray was patchy shadows.In group Ⅱ (bronchoscopic instillation,100 CFU) and group Ⅲ (intratracheal instillation,100 CFU) the disease developed rapidly,and the main manifestation of chest X-ray was patchy and nodular lesions during the 4th to the 12th week postinfection,but became large patchy and consolidation lesions during the 12th to the 24th week postinfection.Tuberculosis granuloma and caseous necrosis,similar to the pathological changes of human tuberculosis,were found in the lungs,mediastinaI lymph nodes,kidney and spleen.The results of acid-fast stain were positive.The most serious pathological manifestations were observed in group Ⅱ,followed by group Ⅲ and group Ⅰ.The highest bacterial load of the right lung was seen in group Ⅱ,followed by group Ⅰ and group Ⅲ.Conclusions A chinese rhesus model of tuberculosis was successfully developed via both bronchoscopic and intratracheal instillation.Their clinical manifestations,disease progression and pathological changes were similar to human primary tuberculosis and hematogenous disseminated tuberculosis.