异烟肼对耐药性结核小鼠肺和脾组织的影响分析

Effects of isoniazid on lung and spleen tissues of drug-resistant tuberculosis mice

目的探讨与分析异烟肼对耐药性结核小鼠肺、脾组织的影响。方法研究时间为2017年8月到2018年5月,20只SPF级昆明种小鼠采用静脉注射结核分枝杆菌菌株20153311建立耐药性结核小鼠模型,随机分组两组,观察组给予50 mg/kg异烟肼,对照组根据体重给予空白溶剂,连续给药2周。记录小鼠体重变化,检测血清生化指标[碱性磷酸酶(ALP)、总胆红素(TBA)、丙氨酸氨基转移酶(ALT)、天冬氨酸氨基转移酶(AST)]与肺、脾组织病理情况。结果造模后小鼠进食量减少,细菌培养结果均为阳性,两组小鼠给药前的体重比较差异无统计学意义。给药后体重呈现总体增长趋势(P <0. 05),观察组体重高于对照组(P <0. 05)。观察组的血清ALP、TBA、ALT、AST值高于对照组,差异有统计学意义(P <0. 05)。对照组小鼠肺脏多数可见满布的粟粒样结节,脾脏可见1~2个灰白色结节或肿大,伴有大量的淋巴细胞浸润,脾脏水肿明显。观察组鼠肺脏多散分布在3~8个灰白色结节偶,肝、脾偶可见轻度水肿,可见类上皮细胞及淋巴浸润。对照组中肺、脾组织细胞中出现显著性的凋亡情况,观察组中细胞凋亡比率明显低于对照组(P <0. 05)。结论异烟肼在耐药性结核小鼠中的应用存在药物性肝损伤作用,但是可发挥对肺、脾组织的保护作用。

Objective To investigate and analysis the effects of isoniazid on lung and spleen tissues of drug-resistant tuberculosis mice. Methods The study time were from August 2017 to May 2018. 20 SPF Kunming mice were injected with M. tuberculosis strain 20153311 to establish drug-resistant tuberculosis mouse model and were divided into the 10 mice in the observation group and 10 mice in the control group. The observation group were given 50 mg/kg isoniazid, the control group were given blank solvent accorded to the body weight for 2 weeks. The changes of body weight were recorded, and the serum biochemical indexes and pathological conditions of lung and spleen were detected. Results After the model were established, the mice were reduced food intake and the bacterial culture results were positive. There were no significant difference in body weight compared between the two groups before administration, the body weight showed overall growth trend after administration ( P <0.05), the body weight in the observation group were higher than the control group ( P <0.05). The serum ALP, TBA, ALT and AST values after administration of the observation group were higher than those of the control group, and compared the difference were statistically significant ( P <0.05). In the control group, most of the lungs were covered with miliary nodules, and there were 1~2 gray-white nodules or enlargement were observed in the spleen, accompanied by large amount of lymphocyte infiltration and spleen edema. In the observation group, the lungs were scattered in 3-8 gray-white nodules, and mild edema were observed in the liver and spleen, the epithelial cells and lymphatic infiltration were observed. There were significant apoptosis occurred in the lung and spleen cells of the control group, and the proportion of apoptosis in the observation group were decreased significantly. Conclusion The application of isoniazid in drug-resistant tuberculosis mice has drug-induced liver injury, but it can play a protective role in lung and spleen tissues.