脊柱结核兔模型的建立及研究进展

doi:10.19982/j.issn.1000-6621.20220516

中国防痨杂志 ›› 2023, Vol. 45 ›› Issue (5): 520-525.doi: 10.19982/j.issn.1000-6621.20220516

脊柱结核兔模型的建立及研究进展

杨军¹, 邓强²(), 彭冉东³, 李军杰⁴, 王雨榕⁵, 杨海云¹, 杜健强¹

¹ 甘肃中医药大学研究生院, 兰州 730000
² 甘肃省中医院医务处, 兰州 730050
³ 甘肃省中医院骨髓炎科, 兰州 730050
⁴ 甘肃省中医院脊柱骨二科, 兰州 730050
⁵ 甘肃省中医院脊柱骨三科, 兰州 730050

收稿日期:2023-01-09 出版日期:2023-05-10 发布日期:2023-04-25
通信作者: 邓强 E-mail:znzsjzez@163.com
基金资助:
2021年甘肃省财政转移支付地方项目/中西医结合防治耐药菌研究(20210140305);基于中医临床研究基地优势病种的中医临床疗效评价能力提升(20210200111);脊柱患者术后切口感染相关危险因素及远期预后的回顾分析研究(21JR1RA057)

Establishment and research progress of rabbit model of spinal tuberculosis

Yang Jun¹, Deng Qiang²(), Peng Randong³, Li Junjie⁴, Wang Yurong⁵, Yang Haiyun¹, Du Jianqiang¹

¹ Graduate School of Gansu University of Traditional Chinese Medicine, Lanzhou 730000, China
² Medical Department of Gansu Provincial Hospital of Traditional Chinese Medicine, Lanzhou 730050, China
³ Department of Osteomyelitis, Gansu Provincial Hospital of Traditional Chinese Medicine, Lanzhou 730050, China
⁴ Second Department of Spine and Bone, Gansu Provincial Hospital of Traditional Chinese Medicine, Lanzhou 730050, China
⁵ Third Department of Spine and Bone, Gansu Provincial Hospital of Traditional Chinese Medicine, Lanzhou 730050, China

Received:2023-01-09 Online:2023-05-10 Published:2023-04-25
Contact: Deng Qiang E-mail:znzsjzez@163.com
Supported by:
Gansu Provincial Financial Transfer Payment Local Project in 2021/Research on the Prevention and Treatment of Drug Resistant Bacteria by Integrated Traditional Chinese and Western Medicine(20210140305);Improve the Ability to Evaluate the Clinical Efficacy of Traditional Chinese Medicine Based on the Advantageous Diseases of the Clinical Research Base of Traditional Chinese Medicine(20210200111);Retrospective Analysis of Risk Factors and Long-term Prognosis of Postoperative Incision Infection in Spinal Patients(21JR1RA057)

摘要/Abstract

摘要：

结核病由结核分枝杆菌侵袭人体器官引起。脊柱结核占肺外结核的50%,已成为严重威胁人类健康的骨科疾病,其发病机制尚未完全明确,可使用的抗结核药物和治疗方案有限。动物模型作为研究疾病发病机制及治疗药物的有力工具备受关注。新西兰兔因其腰椎解剖结构与人类相似,骨结核病变表现可以复现人类结核病病理表现,以及构建脊柱结核模型操作方便等特点,广泛用于脊柱结核动物模型实验研究。笔者综述了脊柱结核兔模型构建方法及其在结核病发病机制、抗结核新药研发及局部载药研究中的应用价值,为脊柱结核相关基础研究中兔模型的建立及应用提供参考。

关键词: 结核,脊柱, 疾病模型,动物, 兔, 综述文献(主题)

Abstract:

Tuberculosis is caused by Mycobacterium tuberculosis by invading human organs. Spinal tuberculosis accounts for 50% of extra-pulmonary tuberculosis and has become a serious orthopedic disease that threatens human health. The pathogenesis of spinal tuberculosis has not yet been fully understood, and the available anti-tuberculosis drugs and treatment options are limited. As a powerful tool for studying the pathogenesis of diseases and therapeutic drugs, animal models have received considerable attention. New Zealand rabbits are widely used as animal models in the experimental study of spinal tuberculosis because of their similar anatomical structure of lumbar vertebrae to humans, the manifestation of bone tuberculosis can reproduce the pathological manifestations of human tuberculosis, and the convenient operation of constructing spinal tuberculosis models. This article reviewed the construction method of spinal tuberculosis rabbit models and the application value in the pathogenesis of tuberculosis, the development of new anti-tuberculosis drugs and local drug loading research, to provide reference for the establishment and application of rabbit models in basic research related to spinal tuberculosis.

Key words: Tuberculosis, spinal, Disease models, animal, Rabbits, Review literature as topic

中图分类号:

R529.2

杨军, 邓强, 彭冉东, 李军杰, 王雨榕, 杨海云, 杜健强. 脊柱结核兔模型的建立及研究进展[J]. 中国防痨杂志, 2023, 45(5): 520-525. doi: 10.19982/j.issn.1000-6621.20220516

Yang Jun, Deng Qiang, Peng Randong, Li Junjie, Wang Yurong, Yang Haiyun, Du Jianqiang. Establishment and research progress of rabbit model of spinal tuberculosis[J]. Chinese Journal of Antituberculosis, 2023, 45(5): 520-525. doi: 10.19982/j.issn.1000-6621.20220516

图/表 1

参考文献 41

[1]	Khanna K, Sabharwal S. Spinal tuberculosis: a comprehensive review for the modern spine surgeon. Spine J, 2019, 19(11):1858-1870. doi:10.1016/j.spinee.2019.05.002. doi: S1529-9430(19)30171-8 pmid: 31102727
[2]	Tang L, Fu CG, Zhou ZY, et al. Clinical Features and Outcomes of Spinal Tuberculosis in Central China. Infect Drug Resist, 2022, 15:6641-6650. doi:10.2147/IDR.S384442. doi: 10.2147/IDR.S384442 pmid: 36386413
[3]	高永建, 欧云生, 权正学, 等. 胸腰椎脊柱结核外科治疗的研究进展. 中国修复重建外科杂志, 2018, 32(1):112-117. doi:10.7507/1002-1892.201705124. doi: 10.7507/1002-1892.201705124
[4]	张中敏, 刘艳芳. 结核分枝杆菌T细胞斑点试验诊断结核性胸膜炎的临床价值. 临床医学研究与实践, 2017, 2(24):45-46. doi:10.19347/j.cnki.2096-1413.201724022. doi: 10.19347/j.cnki.2096-1413.201724022
[5]	Guo XH, Bai Z, Qiang B, et al. Roles of monocyte chemotactic protein 1 and nuclear factor-kappaB in immune response to spinal tuberculosis in a New Zealand white rabbit model. Braz J Med Biol Res, 2017, 50(3):e5625. doi:10.1590/1414-431X20165625. doi: 10.1590/1414-431X20165625 URL
[6]	Gong W, Liang Y, Wu X. Animal Models of Tuberculosis Vaccine Research: An Important Component in the Fight against Tuberculosis. Biomed Res Int, 2020, 2020:4263079. doi:10.1155/2020/4263079. doi: 10.1155/2020/4263079
[7]	Zhan L, Tang J, Sun M, et al. Animal Models for Tuberculosis in Translational and Precision Medicine. Front Microbiol, 2017, 8:717. doi:10.3389/fmicb.2017.00717. doi: 10.3389/fmicb.2017.00717 pmid: 28522990
[8]	Gupta T, Somanna N, Rowe T, et al. Ferrets as a model for tuberculosis transmission. Front Cell Infect Microbiol, 2022, 12:873416. doi:10.3389/fcimb.2022.873416. doi: 10.3389/fcimb.2022.873416 URL
[9]	Creissen E, Izzo L, Dawson C, et al. Guinea Pig Model of Mycobacterium tuberculosis Infection. Curr Protoc, 2021, 1(12):e312. doi:10.1002/cpz1.312. doi: 10.1002/cpz1.312
[10]	Bucsan AN, Mehra S, Khader SA, et al. The current state of animal models and genomic approaches towards identifying and validating molecular determinants of Mycobacterium tuberculosis infection and tuberculosis disease. Pathog Dis, 2019, 77(4):ftz037. doi:10.1093/femspd/ftz037. doi: 10.1093/femspd/ftz037 URL
[11]	Dannenberg Jr AM. Pathogenesis of pulmonary Mycobacterium bovis infection: basic principles established by the rabbit model. Tuberculosis (Edinb), 2001, 81(1-2):87-96. doi:10.1054/tube.2000.0260. doi: 10.1054/tube.2000.0260 URL
[12]	Dannenberg Jr AM. Liquefaction and cavity formation in pulmonary TB: a simple method in rabbit skin to test inhibitors. Tuberculosis (Edinb), 2009, 89(4):243-247. doi:10.1016/j.tube.2009.05.006. doi: 10.1016/j.tube.2009.05.006 URL
[13]	Manabe YC, Dannenberg AJ, Tyagi SK, et al. Different strains of Mycobacterium tuberculosis cause various spectrums of disease in the rabbit model of tuberculosis. Infect Immun, 2003, 71(10):6004-6011. doi:10.1128/IAI.71.10.6004-6011.2003. doi: 10.1128/IAI.71.10.6004-6011.2003 URL
[14]	Popov BV, Sutula GI, Petrov NS, et al. Preparation and charac-terization of the antibody recognizing AMACR inside its catalytic center. Int J Oncol, 2018, 52(2):547-559. doi:10.3892/ijo.2017.4220. doi: 10.3892/ijo.2017.4220
[15]	Liu P, Jiang H, Li S, et al. Determination of anti-tuberculosis drug concentration and distribution from sustained release microspheres in the vertebrae of a spinal tuberculosis rabbit model. J Orthop Res, 2017, 35(1):200-208. doi:10.1002/jor.23236. doi: 10.1002/jor.23236 pmid: 26996958
[16]	Yue X, Zhu X, Wu L, et al. A comparative study of a rabbit spinal tuberculosis model constructed by local direct infection via the posterior lateral approach. Sci Rep, 2022, 12(1):12853. doi:10.1038/s41598-022-16624-2. doi: 10.1038/s41598-022-16624-2 pmid: 35896778
[17]	乔永杰, 李松凯, 甄平, 等. 不同浓度结核菌建立兔脊柱结核模型的对比研究. 中国矫形外科杂志, 2017, 25(5):459-465. doi:10.3977/j.issn.1005-8478.2017.05.15. doi: 10.3977/j.issn.1005-8478.2017.05.15
[18]	Geng G, Wang Q, Shi J, et al. Establishment of a New Zea-land Rabbit Model of Spinal Tuberculosis. J Spinal Disord Tech, 2015, 28(3):E140-E145. doi:10.1097/BSD.0000000000000191. doi: 10.1097/BSD.0000000000000191 URL
[19]	涂振阳, 蓝常贡, 谢克恭, 等. 兔结核病模型的应用研究进展. 微生物学杂志, 2019, 39(6):102-108. doi:10.3969/j.issn.1005-7021.2019.06.014. doi: 10.3969/j.issn.1005-7021.2019.06.014
[20]	Andre E, Isaacs C, Affolabi D, et al. Connectivity of diagnostic technologies: improving surveillance and accelerating tuberculosis elimination. Int J Tuberc Lung Dis, 2016, 20(8):999-1003. doi:10.5588/ijtld.16.0015. doi: 10.5588/ijtld.16.0015 pmid: 27393530
[21]	罗飞. 脊柱结核的治疗. 中华骨科杂志, 2014, 34(5):598.
[22]	中国防痨协会临床专业委员会. 结核病临床诊治进展年度报告(2011年). 中国防痨杂志, 2012, 34(6):393-403.
[23]	侯长浩, 路小欢, 陆雪儿, 等. 新型结核疫苗的研究进展. 中国病原生物学杂志, 2018, 13(8):925-929. doi:10.13350/j.cjpb.180830. doi: 10.13350/j.cjpb.180830
[24]	Liu X, Jia W, Wang H, et al. Establishment of a rabbit model of spinal tuberculosis using Mycobacterium tuberculosis strain H37Rv. Jpn J Infect Dis, 2015, 68(2):89-97. doi:10.7883/yoken.JJID.2014.147. doi: 10.7883/yoken.JJID.2014.147 URL
[25]	陈振, 吴鹏, 马荣, 等. 构建新西兰兔脊柱结核模型的实验研究. 宁夏医科大学学报, 2015, 37(10):1124-1127. doi:10.16050/j.cnki.issn1674-6309.2015.10.003. doi: 10.16050/j.cnki.issn1674-6309.2015.10.003
[26]	耿广起. 新西兰兔脊柱结核模型的构建及评价相关实验研究. 银川:宁夏医科大学, 2012.
[27]	Liu X, Wang Y, Jia W. Early diagnosis of spinal tuberculosis by magnetic resonance: perfusion weighted imaging in a rabbit model. BMC Med Imaging, 2022, 22(1):142. doi:10.1186/s12880-022-00870-x. doi: 10.1186/s12880-022-00870-x pmid: 35945512
[28]	蒲育, 环明苍. 脊柱结核并发HIV感染/AIDS患者的诊治现状与进展概述. 中国防痨杂志, 2020, 42(5):428-435. doi:10.3969/j.issn.1000-6621.2020.05.004. doi: 10.3969/j.issn.1000-6621.2020.05.004
[29]	范顺武, 胡子昂. 重视脊柱结核化学药物治疗的重要性. 中国骨伤, 2017, 30(9):783-786. doi:10.3969/j.issn.1003-0034.2017.09.001. doi: 10.3969/j.issn.1003-0034.2017.09.001
[30]	Hasenoehrl EJ, Wiggins TJ, Berney M. Bioenergetic Inhibitors: Antibiotic Efficacy and Mechanisms of Action in Mycobacterium tuberculosis. Front Cell Infect Microbiol, 2020, 10:611683. doi:10.3389/fcimb.2020.611683. doi: 10.3389/fcimb.2020.611683 URL
[31]	中国防痨协会. 耐药结核病化学治疗指南(2019年简版). 中国防痨杂志, 2019, 41(10):1025-1073. doi:10.3969/j.issn.1000-6621.2019.10.001. doi: 10.3969/j.issn.1000-6621.2019.10.001
[32]	邓强, 李军杰, 张彦军, 等. 复治脊柱结核规范化治疗的再认识与思考. 兰州大学学报(医学版), 2019, 45(4):54-60. doi:10.13885/j.issn.1000-2812.2019.04.011. doi: 10.13885/j.issn.1000-2812.2019.04.011
[33]	Wang XW, Liu JJ, Wu QN, et al. The in vitro and in vivo effects of microRNA-133a on intervertebral disc destruction by targeting MMP9 in spinal tuberculosis. Life Sci, 2017, 188:198-205. doi:10.1016/j.lfs.2017.07.022. doi: 10.1016/j.lfs.2017.07.022 URL
[34]	Wang W, Yang B, Cui Y, et al. Isoliquiritigenin attenuates spinal tuberculosis through inhibiting immune response in a New Zealand white rabbit model. Korean J Physiol Pharmacol, 2018, 22(4):369-377. doi:10.4196/kjpp.2018.22(4):369-377. doi: 10.4196/kjpp.2018.22.4.369 URL
[35]	Zhao Y, Jiao Y, Wang L. Hesperidin methyl chalcone alleviates spinal tuberculosis in New Zealand white rabbits by suppressing immune responses. J Spinal Cord Med, 2020, 43(4):532-539. doi:10.1080/10790268.2018.1507805. doi: 10.1080/10790268.2018.1507805 pmid: 30124375
[36]	周文强, 张爽, 初乃惠. 耐药肺结核全口服治疗方案研究的现状和展望. 中国防痨杂志, 2021, 43(9):879-882. doi:10.3969/j.issn.1000-6621.2021.09.005. doi: 10.3969/j.issn.1000-6621.2021.09.005
[37]	戈朝晖, 马荣, 陈振, 等. 载异烟肼及利福平白蛋白纳米粒治疗兔脊柱结核的实验观察. 中国脊柱脊髓杂志, 2018, 28(3):253-261. doi:10.3969/j.issn.1004-406X.2018.03.10. doi: 10.3969/j.issn.1004-406X.2018.03.10
[38]	黄正辉, 刘炜, 王静丽. 脂肪间充质干细胞复合利福平缓释微球在脊柱结核动物模型中的应用. 中国组织工程研究, 2017, 21(26):4192-4198. doi:10.3969/j.issn.2095-4344.2017.26.016. doi: 10.3969/j.issn.2095-4344.2017.26.016
[39]	Ma R, Zhang J, Chen Z, et al. Treatment of spinal tuberculosis in rabbits using bovine serum albumin nanoparticles loaded with isoniazid and rifampicin. Neurol Res, 2022, 44(3):268-274. doi:10.1080/01616412.2021.1979749. doi: 10.1080/01616412.2021.1979749 URL
[40]	Wang Z, Maimaitiaili A, Wang T, et al. Rifapentine Polylactic Acid Sustained-Release Microsphere Complex for Spinal Tuberculosis Therapy: Preparation, in vitro and in vivo Studies. Infect Drug Resist, 2021, 14:1781-1794. doi:10.2147/IDR.S304864. doi: 10.2147/IDR.S304864 URL
[41]	赵皎洁, 陆宇. 抗结核药物药代动力学/药效学的研究及进展. 中国防痨杂志, 2019, 41(6):700-704. doi:10.3969/j.issn.1000-6621.2019.06.020. doi: 10.3969/j.issn.1000-6621.2019.06.020

实验动物	优点	缺点
豚鼠	对结核分枝杆菌非常敏感,其肉芽肿结构典型,可发展为坏死,与人类结核病肉芽肿相似	体型过小,不适合脊柱结核造模操作^[9]
小鼠	遗传背景清楚,价格低廉,有较成熟的定向基因敲除技术	一般不出现坏死,很难在小鼠模型上观察到干酪样坏死。脊柱椎体细小,不适合进行脊柱手术操作^[10]
非人类灵长类动物	遗传物质与人类同源,在生理、形态和机能上相近,与人类的生物学和行为学特性相似	费用较高,实验室内饲养较难,且数量有限^[16]
兔	腰椎解剖结构、骨结核病变表现等与人类相似,易于脊柱手术操作	对结核分枝杆菌易感性相对较差^[12-13]

脊柱结核兔模型的建立及研究进展

Establishment and research progress of rabbit model of spinal tuberculosis

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