分枝杆菌所致家兔皮肤液化病理模型研究

An examination of a rabbit model of liquefaction induced by Mycobacterium

目的建立卡介苗(BCG)、H37Ra和耻垢分枝杆菌感染的新西兰兔皮肤模型,为肺结核干酪样坏死和继而发生的液化提供研究模型。方法新西兰兔皮内分别注射BCG、H37Ra和耻垢分枝杆菌的5×106CFU、5×104CFU、5×102CFU/ml菌液,6周后在病灶周围再次以相同剂量皮内注射,14d后病变明显时取材,制作切片,行HE染色,显微镜下观察。结果新西兰兔分别经皮内接种BCG、H37Ra或耻垢分枝杆菌后,高剂量组观察到明显的炎症反应和脓肿液化、破溃等改变。再次免疫可观察到郭霍现象。引起病变的严重程度依次为BCG强于H37Ra,后者又强于耻垢分枝杆菌。显微改变可具典型的结核结节样病灶。皮肤模型处取材,行细菌抗酸染色,结果阳性。BCG中、低剂量组再次免疫可诱导小结节样病变,但不发生液化溃疡,其余中剂量组及低剂量组没有观察到明显改变。结论BCG、H37Ra和耻垢分枝杆菌均可引起皮肤干酪样坏死和液化,病理损伤与感染细菌剂量密切相关,5×106CFU/ml浓度的分枝杆菌可有效诱导液化和坏死,其中BCG引起的病理改变最明显。

Objective In order to investigate the mechanism of tuberculosis pathology, in particular the mechanism of liquefaction, studies are conducted to establish a tuberculosis pathology model in rabbit skin using Mycobacterium bovis attenuated strain BCG, Mycobacterium tuberculosis avirulent strain H37Ra, and Mycobacterium smegrnatis（M, smegmatis） . Methods BCG, H37Ra, and M. smegmatis were injected separately into the flank of New Zealand white rabbits by intradermal route twice every one and half months. Fourteen days after the last injection, lesions were removed for further histological analysis. Results Apparent liquefaction and ulceration were produced in the skin of rabbits injected with high dose（5 × 10^6CFU/ml） of BCG, H37Ra, and M. smegmatis, with ulceration happening around 10 days after the first injection and three days after second immunization. The inflammation induced by BCG was stronger than the lesion induced by H37Ra, and the latter was stronger than that induced by M. snwgmatis. Moderate（5 × 10^4 CFU/ml）and low doses （5 × 10^2 CFU/ml） of H37Ra and M. smegmatis did not induce obvious lesions, while the moderate and low doses of BCG induced granulomas. Conclusion High dose of BCG, H37Ra and M. smegmatis could induce caseous necrosis and liquefaction in rabbit skin. These results demonstrate the usefulness of this model for further pathogenesis research.