腺苷提高小鼠接种卡介苗后抗结核杆菌效力的研究

Adenosine enhances antibacterial effect of bacille calmette guerin against mycobacterium tuberculosis in mice

目的通过观察小鼠肺组织结核病理改变,探讨腺苷（ADO）能否提高卡介菌（BCG）接种效果.方法将BALB/C小鼠随机分为BCG组、ADO组和对照组.实验开始时BCG组、ADO 2组均皮内注射BCG 0.1 ml,接种BCG当天起,ADO组腹腔注射ADO 30 mg·kg^-1·d^-1,BCG组和对照组腹腔注射生理盐水0.1 ml/d,共5 d.6周后以人型结核分枝杆菌标准毒力株经血液途径攻击每组小鼠.BCG组、ADO组于结核杆菌感染后第10、20、30 d取肺HE染色和抗酸染色观察,对照组于第30天取材.结果对照组结核杆菌感染后第30天,肺组织大部分实变,以中性粒细胞浸润为主,结核结节多,肺内弥漫分布大量菌体;BCG组于感染后第10～30 d肺组织实变面积逐渐增大,结核结节较少,间质内浸润单核细胞、淋巴细胞、中性粒细胞,单核细胞破损较多,肺内大量菌体.而ADO组于感染后第10～30 d小鼠肺实变面积小,结核结节很少,间质内以单核细胞和淋巴细胞浸润为主,大多数单核细胞完整,肺内菌体明显减少.结论腺苷减轻了肺组织结核病变,增加能够杀灭结核杆菌的单核-巨噬细胞数量,其能增强卡介苗抗结核杆菌的免疫效力.

Objective To investigate if adenosine （ADO） can enhance the effect of BCG against Mycobacterium tuberculosis by observing pathological changes of lung tissue in mice. Methods Forty eight BALB/c mice were randomized into BCG group （n = 21）, BCG plus ADO group （n = 21） and control group （n = 6）. At first the mice in BCG and BCG plus ADO groups were given intradermal BCG vaccination. When vaccinated with BCG, the mice of BCG plus ADO group were treated by intraperitoneal injection with adenosine 30 mg·kg^-1·d^-1 for five days, while the other two groups were given intraperitoneal injection with saline 0.1 ml/d for five days. At the sixth week after BCG vaccination ,the mice of every group were intravenously infected with 1×10^6 CFU human Mycobacterium tuberculosis virulent strain. At the 10, 20 and 30th day the mice in BCG group and BCG plus ADO group were observed for HE dyeing and avld-fast staining and the same was done on control group on the 30th day. Results Consolidation with neutrophil infiltration was found in most lung tissues in control group, and there were a lot of tuberculosis granulomas and Myeobaeterium tuberculosis in the lungs of control group. From the 10th to 30th day after challenging in BCG group lung tissue consolidation became gradually wide, less tuberculous granulomas and in interstitium the infiltration of monoctytes, lymphoeytes and neutrophils were observed, but considerable monocytes were damaged and there were large mumber of Mycobacterium tuberculosis in the lungs. Consolidation of lung tissue in BCG plus ADO group became milder with no much damaged monocytes infiltration,and there were few tuberculosis granulomas and mycobacterium tuberculosis in the lungs from the 10th to 30th day after challenging. Conclusion ADO could lessen pathological changes of tuberculosis in the lungs and increase the number of monocytes-macrophages which may kill Mycobacterium tuberculosis. It could enhance the immunity of the mice vaccinated with BCG against M tuberculosis.