获得性异位骨化动物模型的系统综述

目的 系统综述获得性异位骨化(AHO)相关动物模型,为研究疾病防治方案提供可靠造模方法。方法 检索PubMed、Web of Science、中国知网、万方数据库自建库至2021年11月AHO动物模型相关文献,筛选并提取文献关键内容,采用文献归纳法对各型AHO动物模型进行分析与评价。结果 最终共纳入20篇动物实验研究相关文献,可归纳为创伤后和神经源性两大类异位骨化动物模型,用于模拟AHO的发生发展过程。创伤后异位骨化动物模型主要有肌肉损伤、跟腱切断、肌肉损伤联合关节制动、髋关节损伤、异位植入、爆炸伤和烧伤7种。神经源性异位骨化动物模型主要包括脊髓损伤和脑外伤。目前实验室中常用跟腱切断法和成骨因子植入法造模,此类方法可靠、易行、成功率高,但无法准确解释临床中复杂条件下异位骨化的发病机制。基于爆炸伤、烧伤、神经损伤等条件下造模方法正在完善,为临床研究某些特殊病因所致异位骨化的分子生物学机制及防治方案提供了支持。结论 目前存在的几种造模方法各有利弊,但均无法完整复制人类异位骨化的全部特征,因此,临床上在判定模型的选择方面尚无统一标准。针对疾病的不同病因,选用合适的动物模型,对不同类型AHO在早期制定有效干预措施至关重要。

Animal models of acquired heterotopic ossification: a systematic review

Objective To systematically summarize the animal models of acquired heterotopic ossification (AHO), and provide reliable modeling methods for the study of disease prevention and treatment programs.Methods Literatures about the animal models of AHO were researched from PubMed, Web of Science, CNKI and Wanfang Database till November, 2021. The important contents of the literatures were extracted, and the animal models of various types of AHO were evaluated and analyzed by literature induction.Results A total of 20 literatures related to animal experiments were included, which could be divided into two types: post-traumatic and neurogenic heterotopic ossification animal models, which were used to simulate the occurrence and development of AHO. Currently, seven different animal models were commonly used to study post-traumatic heterotopic ossification, such as muscle injury, achilles tenotomy, muscle injury combined with joint immobilization, hip injury, heterotopic implantation, blast injury and burn. The studies of neurogenic heterotopic ossification animal models mainly included spinal cord injury and traumatic brain injury. At present, the methods of achilles tenotomy and osteogenic factor implantation were commonly used in the laboratory, and with the advantages of reliability, feasibility and high success rate; however, they could not accurately explain the pathogenesis of heterotopic ossification under complicated clinical conditions. Therefore, the improvement of modeling methods based on explosion injury, burn, nerve injury and other conditions became the basis for clinical research of molecular biological mechanism, prevention and treatment of heterotopic ossification.Conclusion Current modeling methods have their own advantages and disadvantages, but none of them can completely replicate all the characteristics of human heterotopic ossification. Therefore, there is no unified standard in the selection of animal model in clinic. According to different etiology of the disease, the selection of appropriate animal models is crucial to study effective intervention for different types of AHO in the early stage.