动物造模,创伤后骨关节炎 z-bio 2021-12-07 1166

　　Abstract: Osteoarthritis (Osteoarthritis, OA) is a common inflammatory joint disease that affects the growth and development of the elderly and has a strong socio-economic impact. Post-traumatic osteoarthritis is a kind of post-traumatic osteoarthritis animal used to study osteoarthritis. Because its etiology and etiology are not clear, it is difficult to recover due to the lack of effective clinical diagnosis and treatment. It is necessary and necessary to establish a model . This is urgent. Animal models of traumatic osteoarthritis use a variety of artificial methods to select different animal species, including progressive cartilage damage, subchondral bone remodeling, osteophyte formation, and inflammation of the soft tissues around the joints, which can induce physical processes. This article reviews the research methods and current status of post-traumatic osteoarthritis animal models, covering the past 10 years of overseas academic papers, and provides a suitable reference method for establishing post-traumatic osteoarthritis animal models.

　　Conclusion: Extra-articular induction: tibial compression overload model Christiansen et al. used a tibial compression system composed of two custom load-bearing plates made by C57BL/6N mice and a tibial compression method with an overload cycle, and then established an animal model. The lower pedal bends the knees, and the upper pedal bends the feet and ankles at an angle of about 30°. A single dynamic axial compression load was then 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 movement of articular cartilage and joint stress environment, this modeling method is very important. Artificially increasing or reducing joint pressure can lead to post-traumatic osteoarthritis (PTOA). Bone matrix damage is caused by artificially increasing or decreasing stress. Due to the compensatory hypertrophy and degeneration of chondrocytes, cartilage degeneration occurs throughout the cartilage joints of the animal. Satkunananthan? et al. used C57BL/6N mice to experimentally replicate the post-traumatic osteoarthritis model. Killian et al. successfully established a post-traumatic osteoarthritis model, which resulted in blunt trauma to the tibiofemoral joint in rabbits under axial compression loading. Tochigi et al. used pigs to successfully create a model of post-traumatic elbow osteoarthritis. The elbow joint is overloaded due to axial compression. Borrelli et al. repositioned the overload. A New Zealand white rabbit was successfully compressed on the inside of the femoral condyle to simulate the post-traumatic process of osteoarthritis.

　　Intra-articular surgery: Anterior cruciate ligament rupture, ACLT model: Pond et al. performed an anterior cruciate ligament rupture in a posterior knee joint of 10 dogs, and the contralateral joint was used as a control. The animals were sacrificed at different times from 1 to 26 weeks after the operation. Radiological and pathological examinations showed that a human post-traumatic osteoarthritis model was successfully established. This modeling principle usually indicates that the tibia is constrained by the anterior cruciate ligament and needs to limit excessive movement. After the anterior cruciate ligament resection of the animal model, the tibia and the knee joints of the hind limbs rotate inward and move forward, increasing the flexion and extension process of the hind limbs and knee joints of the animal, destroying the stability of the joints, and ultimately leading to post-traumatic osteoarthritis (PTOA). The canine ACLT model proved that the animal returned to the preoperative level 5 months after ACLT operation by observing the ground reaction force (GRF) and the mechanical data of the posterior knee joint. Boyd et al. divided 13 cats into three groups and established a human-like ptoa model using the same anterior cruciate ligament amputation method to eliminate species-specific interference in the animal model. ...Then use micro-CT to observe the long-term effects of the bones around the joints (including the proximal tibial subchondral bone, femoral condyle, and end cancellous bone) and their role in the etiology of post-traumatic osteoarthritis. Character. Agai et al. established a rabbit model of post-traumatic osteoarthritis using Japanese white rabbits and ACTL technology. 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 three groups, cut the rabbit’s right hind knee joint from the anteromedial side, opened the middle section of the knee joint, and exposed it. The anterior part of the medial meniscus (1/3 related to the meniscus) is used to establish a human PTOA model. Arunakul? et al. performed a complete meniscus resection (TMM) operation using a PTOA model created by 16 New Zealand white rabbits. As a result, the medial meniscus of the animal's knee joint becomes unstable. Panahfar et al. used the medial meniscus excision (MMX) technique to establish a human post-traumatic osteoarthritis model using SD rats. The DMM model modeling process takes longer than the aforementioned ACTL model. Glasson et al. used ADAMTS-4 and ADAMTS-5 knockout mice to assess the degree of cartilage damage through a histological scoring system, and compared ACTL and DMM models. The results show that the ACTL model can simulate a more serious human PTOA process. Some ACTL animals showed severe posterior cartilage erosion and osteophyte formation on the tibial plateau. In contrast, the DMM model is less invasive, with only mild injuries in the center of the tibial plateau and femoral condyle. Therefore, Glasson et al. believe that DMM is the preferred surgical method for mouse post-traumatic osteoarthritis models. Usmani et al. successfully established a mouse PTOA model in experiments using the above-mentioned forming method.

　　Hulth Model/Modified Hulth Model: Hulth et al. conducted experiments with 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 PTOA features such as cartilage surface cracks and cartilage surface damage were observed within 3 months after Hulth. Hals’ operation destroyed the main ligaments that maintain the static stability of the animal’s knee joints, including the anterior cruciate ligament and the medial collateral ligament. Results The normal force line of the knee joint changed from 10° valgus to varus, the axial pressure of the joint changed, the lateral tibial platform moved to the inside, and the joint stress surface decreased. In addition, stress concentration will increase the compression of local articular cartilage, impair joint stability, increase joint surface wear, and ultimately lead to PTOA. Moskowitz et al. believe that the traditional Hals model has more 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 rarely used for animal model drug intervention. There are currently 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 Hals model. A cruciate ligament rupture (CLT) is a surgical procedure in which only the anterior cruciate ligament is removed without touching the rest of the static structure.

　　Anterior cruciate ligament (ACL) autograft anatomical reconstruction, ACL-R model: Considering the various modeling methods mentioned above, all methods will destroy the stable structure of joints and articular surfaces. Increase wear and use other methods. However, in the long run, even if the cruciate ligament has been reconstructed and the joint structure is relatively stable, some patients still have PTOA. In order to better understand and study the etiology of PTOA, Heard et al. applied autologous ligament transplantation and reconstruction after sheep ACL surgery, and finally formed a human PTOA model. Two weeks after surgery, matrix metalloproteinases and interleukin-like PTOA inflammation markers increased in 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 is considered an ideal large animal model for early diagnosis and treatment of PTOA (especially the catabolism mechanism of inflammatory factors).

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

　　Animal models of traumatic osteoarthritis have different characteristics depending on the animals used and the modeling methods. The PTOA model does not have a standard animal model. The author comprehensively considered factors such as project funds, experimental purposes, technical conditions, etc., selected appropriate experimental animals and modeling methods, obtained appropriate PTOA models and expected experimental results, and provided guidance for clinical treatment. It is now planned to provide.