动物造模,创伤后骨关节炎,动物模型 z-bio 2021-01-14 1206

　　Introduction: Osteoarthritis (OA) is a common inflammatory joint disease that affects the growth of the elderly and has a strong socio-economic impact. As the pathogenesis and etiology of post-traumatic osteoarthritis are not clear, and the lack of effective clinical diagnosis and treatment measures, it is difficult to recover. Therefore, it is necessary and necessary to establish a post-traumatic osteoarthritis animal model to study osteoarthritis. urgent. Animal models of traumatic osteoarthritis can select different animal species through a variety of artificial methods to induce pathological processes such as progressive cartilage injury, subchondral bone reconstruction, osteophyte formation, and inflammation of soft tissues around joints. This article reviews the research methods and current research status of post-traumatic osteoarthritis animal models, covering academic papers in the past ten years abroad, and provides a suitable reference method for the establishment of post-traumatic osteoarthritis animal models.

　　 Conclusion: Extra-articular induction: tibial compression overload model Christiansen et al. used C57BL/6N mice and an overload cycle tibial compression method to establish a post-traumatic animal model using a tibial compression system composed of two custom loading plates. The bottom pedal bends the knees, and the top pedal makes the feet and ankles approximately 30°. Then, a single dynamic axial compression load was applied to the right leg of each mouse, resulting in a temporary anterior subluxation of the tibia relative to the distal femur. In view of the normal activities of articular cartilage and joint stress environment, this modeling method is of great significance. Artificially increasing or reducing joint stress can lead to post-traumatic osteoarthritis (PTOA). Bone matrix damage is caused by artificially increasing or decreasing stress. Due to compensatory hypertrophy and degeneration of chondrocytes, cartilage degeneration occurs in the entire animal cartilage joints. Satkunananthan? et al. used C57BL/6N mice to successfully replicate the post-traumatic osteoarthritis model in experiments. Killian et al. successfully established a post-traumatic osteoarthritis model, which caused rabbits to perform blunt force damage to the tibiofemoral joint under the condition of compression axial overload. Tochigi and others used pigs to successfully create a model of osteoarthritis after elbow joint trauma. The elbow joint is overloaded by axial compression. Borrelli and others changed the position of the overload. New Zealand white rabbits received compression of the medial femoral condyle, successfully simulating the process of human post-traumatic osteoarthritis.

　　 Intra-articular surgery: anterior cruciate ligament transection, ACLT model: Pond et al. performed anterior cruciate ligament transection surgery on one hind knee joint of 10 dogs, and the contralateral joint was used as a control. Animals were sacrificed at different times 1 to 26 weeks after the operation. Radiological and pathological examinations show that the human post-traumatic osteoarthritis model has been successfully established. This modeling principle usually indicates that the tibia should be constrained by the anterior cruciate ligament to limit its excessive movement. After the anterior cruciate ligament resection of the animal model, the knee joints of the tibia and hind limbs rotate inward and move forward, which increases the flexion and extension process of the animal's hind limbs and knee joints, leading to the destruction of joint stability and ultimately leading to post-traumatic osteoarthritis (PTOA). The ACLT model of the canine animal showed that by observing the ground reaction force (GRF) and the mechanical data of the posterior knee joint, it was proved that the animal returned to the preoperative level 5 months after the ACLT operation. Boyd et al. divided 13 cats into 3 groups and used the same anterior cruciate ligament transection method to establish a human-like ptoa model to eliminate the interference of species differences in animal models. Then, micro-CT was used to observe the long-term effects of the bones around the joints (including the proximal tibial subchondral bone, femoral condyle, and metaphyseal cancellous bone), and to evaluate its role in the pathogenesis of post-traumatic osteoarthritis. Nagai et al. used Japanese white rabbits and ACTL technology to establish a rabbit model of post-traumatic osteoarthritis. Dong et al. successfully created a mouse ptoA model, and Mevel et al. used New Zealand white rabbits to create a human ptoA model. Medial meniscus instability, DMM model: Moskowitz et al. divided 82 New Zealand white rabbits into 3 groups. Under aseptic conditions, the rabbit’s right hind knee joint was incised from the anteromedial side to expose the middle compartment of the knee joint, and the inner side was removed. The first half of the meniscus attachment (related to 1/3 of the meniscus), a human PTOA model was established. Arunakul? et al. used 16 New Zealand white rabbits to make a PTOA model, using a total meniscus resection (TMM) surgical method, resulting in instability of the medial meniscus of the animal’s knee joint. Panahfar et al. used the medial meniscus resection (MMX) technique to establish a human post-traumatic osteoarthritis model using SD rats. The modeling process of the DMM model takes longer than the aforementioned ACTL model. Glasson et al. used ADAMTS-4 and ADAMTS-5 gene knockout mice to assess the degree of cartilage damage through a histological scoring system, and compared the ACTL model and the DMM model. The results show that the ACTL model can simulate more serious human PTOA process. Some of the ACTL animals showed severe posterior subchondral bone erosion and osteophyte formation in the tibial plateau. In contrast, the DMM model has fewer invasions, and only mild injuries are shown in the tibial plateau and the middle of the femoral condyle. Therefore, Glasson et al. believe that DMM is the preferred method of operation for mouse post-traumatic osteoarthritis models. Usmani et al. used the above-mentioned forming method in their experiments and successfully established a mouse PTOA model.

　　 Hulth model/modified Hulth model: Hulth et al. conducted experiments on rabbits, removed the anterior cruciate ligament and the medial collateral ligament, completely removed the medial meniscus, and successfully created a human PTOA model. Histological observations showed that the characteristics of PTOA, such as cartilage surface cracks and cartilage surface damage, were observed within 3 months after Hulth. Hulth's operation destroyed the main ligaments (including the anterior cruciate ligament and medial collateral ligament) that maintain the static stability of the animal's knee joint. As a result, the normal line of force of the knee joint changes from valgus 10° to varus, the axial pressure of the joint changes, the lateral tibial plateau moves to the medial, and the weight bearing surface of the joint decreases. In addition, the stress concentration increases the compression of the local articular cartilage, leading to joint stability damage and increased joint surface wear, which ultimately leads to PTOA. Moskowitz et al. believe that the traditional Hulth model causes greater trauma and joint damage, and the biochemical and metabolic changes of PYOA cannot be observed. Due to the short model time and therapeutic intervention time, Hulth model PTOA is less used in animal model drug intervention. Currently, there are improved Hulth models, such as ACLT+partial meniscus resection (PM). The surgical method is ACLT+ medial meniscus resection. In ACLT + medial collateral ligament (MCLT) + medial meniscus resection (MX) surgery, the purpose of the surgery is to maintain the integrity of the posterior cruciate ligament, and the rest of the surgery is the same as the traditional Hulth model. In cruciate ligament transection (CLT), the surgical method is to remove only the anterior cruciate ligament, and the rest of the static structure is not touched. Anterior cruciate ligament (ACL) autograft anatomical reconstruction, ACL-R model: In view of the various modeling methods mentioned above, all methods focus on destroying the stable structure of the joint, increasing the wear of the joint surface, and using other surgical techniques to simulate human PTOA process. However, in the long run, even if the cruciate ligament is reconstructed and the joint structure is relatively stable, some patients will still have PTOA. In order to better understand and explore the pathogenesis of PTOA, Heard et al. applied autologous ligament transplantation reconstruction method after sheep ACL surgery, and finally formed a human PTOA model. Two weeks after the operation, the increase of matrix metalloproteinase and interleukin-like PTOA inflammation markers can be observed in the synovial fluid. This model eliminates the influence of joint structural instability on the incidence of PTOA, and fully understands the influence of inflammatory factors and early catabolism on the incidence of PTOA. Therefore, the author of this article believes that this model is superior to previous models and can be regarded as a kind of Idealized large animal model for early diagnosis and treatment of PTOA (especially the study of inflammatory factors and catabolic mechanisms).

　　 Intra-articular fracture (IAF) model: small pigs, fixed with a special tripod, fixed after 1-2 mm tibia osteotomy of the pig knee, to simulate the course of PTOA. Lewis et al. used C57BL/6 mice to construct a human-like PTOA model by artificial compression axial overload method. Due to equipment limitations (such as special tripods and compression tables) and corresponding internal fixation materials, the author does not recommend this method of modeling.

　　 Animal models of traumatic osteoarthritis have different characteristics, depending on the animal and modeling method used. There is no standard animal model for the PTOA model. The author suggests to select appropriate experimental animals and modeling methods based on the consideration of project funds, experimental objectives and technical conditions, obtain appropriate PTOA models and expected experimental results, and provide guidance for clinical treatment.