关键词: 分枝杆菌, 结核, 豚鼠, 疾病模型, 动物, 维生素D, 化学疗法, 辅助, 疗效比较研究

Abstract:

Objective To establish the chronic Guinea Pig model of tuberculosis and to evaluate the role of adjuvant therapy with Vitamin D.Methods Forty-eight Guinea Pigs infected with Mycobacterium tuberculosis standard strain (H37Rv) were randomly divided into blank control group, daily regular dosage of vitamin D group, single high dosage of vitamin D group taken every other week, isoniazid and rifampicin group, isoniazid and rifampicin plus daily regular dosage of vitamin D group, and isoniazid and rifampicin plus high dosage of vitamin D taken every other week group according to different treatment plans. There were 8 Guinea Pigs in each group. Four weeks after infection, we initiated treatment. 4 Guinea Pigs in each group were weighed, sacrificed, and dissected 4 weeks and 8 weeks after treatment. Later we counted the colony forming unit (CFU). We also performed the pathological examination in lungs and spleens.Results Our model animals had good tolerance and there was no death in each group throughout the infection and treatment. When compared to the control groups, the CFU counts of lungs and spleens of the Guinea Pigs did not decline, and the pathological changes of lungs and spleens did not improve in the two groups treated with vitamin D alone. Besides, after 4 weeks of treatment the CFU of lungs and spleens were (4.98±0.26) lgCFU and (4.02±0.03) lgCFU in the group of isoniazid and rifampicin and (4.39±0.11) lgCFU and (2.30±0.43) lgCFU in the group of isoniazid and rifampicin plus a single high dosage of vitamin D. When compared the group of isoniazid and rifampicin plus a single high dosage of vitamin D every other week with the group of isoniazid and rifampicin alone, the CFU counts decreased by 0.59 lgCFU in lungs and 1.72 lgCFU in spleens. After 8 weeks of treatment the CFU of lungs and spleens were (3.73±0.23) and (2.26±0.24) lgCFU in the group of isoniazid and rifampicin, and the CFU of lungs were (3.21±0.23) lgCFU and spleens were amicrobic in the group of isoniazid and rifampicin plus a single high dosage of vitamin D. When compared the group of isoniazid and rifampicin plus a single high dosage of vitamin D every other week with the group of isoniazid and rifampicin alone, the CFU counts decreased by 0.52 lgCFU in lungs and 2.26 lgCFU in spleens. Also the pathological changes of spleens in the group of isoniazid and rifampicin plus a single high dosage of vitamin D after 4 weeks of treatment improved and so as the lungs in the same group but of 8 weeks of treatment. The CFU of spleens were (2.36±0.10) lgCFU in the group of isoniazid and rifampicin plus daily regular dosage of vitamin D after 4 weeks of treatment. When compared the group of isoniazid and rifampicin plus daily regular dosage of vitamin D with isoniazid and rifampicin alone, the CFU of spleens decreased by 1.66 lgCFU after 4 weeks of treatment.Conclusion In the chronic tuberculosis model of Guinea Pig, vitamin D shows the effect as an adjuvant therapy when combined with isoniazid and rifampicin. It can be further studied to be used for clinical practice.

Key words: Mycobacterium tuberculosis, Guinea pigs, Disease models, animal, Vitamin D, Chemotherapy, adjuvant, Comparative effectiveness research