动物模型 z-bo 2020-08-10 632

　　The normal healing of human and animal skin injuries ends in leaving small and superficial scars. Hypertrophic scars (HS) and keloids are only found in humans and can cause changes in appearance and dysfunction.

　　1 Human hypertrophic scar and keloid tissue transplantation model

　　(1) Reproduction method The nude mice were anesthetized by intraperitoneal injection of sodium pentobarbital at a dose of 30 mg/kg body weight. After anesthesia, the animal was fixed on the surgical board in prone position, and both sides of the back of the mouse were conventionally shaved and disinfected with 75% ethanol. An incision of about 1 cm was made at each of the shoulder blades, and the subcutaneous space was formed by subcutaneous separation, which will be derived from two patients. The hypertrophic scar and keloid tissue were cut into 5mm×5mm×8mm size, implanted in the subcutaneous space, and the incision was sutured with 7-0 non-invasive suture.

　　(2) Model features: Postoperative exploration of the model animals showed that the implanted tissue was quickly bonded to the surface skin and loosely combined with the bottom muscle tissue; the implant changed from a long square to a smooth "pebbles"; the size of the implanted scar tissue There is no obvious difference from before implantation. Whether it is a hypertrophic scar or a keloid implanted tissue, it is covered with a fibrous envelope of different thicknesses when taken out, and the envelope contains a large number of active cells. Blood vessels containing red blood cells can be seen in the capsule and extend into the implant. The implanted hypertrophic scar tissues all kept their original spiral collagen fibers and typical collagen nodules, and there was no significant increase in cells. The implanted keloid tissues all maintained their characteristic hypertrophic refractive eosinophilic collagen bundles, and there was no significant change in the cell composition and density of the implants, and the morphology and density of collagen fibers. Under transmission electron microscopy, fibroblasts and fibroblasts can be seen in the implanted hypertrophic scars and keloids. Fibroblasts contain abundant rough endoplasmic reticulum, which is not significantly different from the original scar tissue. There are obvious granules in the cytoplasm of mast cells.

　　(3) Comparative medicine. Both hypertrophic scars and keloids are characterized by excess extracellular matrix, especially collagen deposition, and their cell morphology is also similar. However, clinically, hypertrophic scars only grow in the original wound and compress the surrounding tissue outwards. After a period of proliferation, it spontaneously degenerates; keloids are excessive scarring caused by the abnormal accumulation of collagen caused by skin injury. They are manifested as excessive growth, exceeding the original wound limit, invading adjacent tissues, and showing tumor-like hyperplasia, causing dysfunction. In the nude mouse models of hypertrophic scars and keloids, the morphology and density of collagen fibers in the implants did not change significantly. Fibroblasts and fibroblasts existed in the implants, and the fibroblasts contained abundant rough endoplasm. The net indicates that the fibroblasts in the implant still maintain the ability to synthesize and secrete collagen, indicating that the implanted scar is still in an "active" state and does not change over time.

　　Studies have reported that human hypertrophic scars and keloid tissues were deepithelized and transplanted under the skin of nude mice. After continuous observation for up to 246 days, it was found that the volume of the grafts decreased to varying degrees, but no rejection occurred. Or changes in histological characteristics such as inflammation, infection response, tissue structure, collagen density, and nodular changes. The shrinkage rate of hypertrophic scar is 0.436% per day, and it shrinks by 1/2 after 115 days; the shrinkage rate of keloid tissue is 0.736% per day, and it shrinks by 1/2 after 67 days. Nevertheless, the time it takes to maintain the characteristics of hypertrophic scars and keloids is sufficient for most laboratory and therapeutic studies. Some scholars have proposed that the use of nude mice as a carrier, due to the small size of the animal and the short survival period, greatly limits the size and survival time of the graft, which is not conducive to ideal observation and measurement of the graft. To this end, they transplanted keloid tissue to a skin flap pedicled with the inferior superficial abdominal artery in nude rats, and made a keloid tissue model. After 12 months of observation, they found that the transplanted keloid tissue is no matter in the tissue structure. The original characteristics of collagen synthesis are maintained, while the activity of fibroblasts cultured from transplants and fibroblasts directly cultured from human keloid tissues are significantly reduced. However, the reactivity of hypertrophic scars transplanted with nude rats as model animals to TGF-β2 is the same as that of human TGF-β2.

　　2 Animal model

　　It has been reported that a full-thickness skin defect wound with deep and cartilage layer was made on the ventral surface of rabbit ears, and continuous observation was carried out for 288 days. As a result, 11 out of 16 wounds (69%) had healed significantly higher skin. The scars on the face are hyperplasia, and the histological examination shows that the collagen fibers in the dermis are arranged disorderly, and characteristic collagen fiber nodules can be seen. Chronic inflammatory changes such as an increase in the number of blood vessels can also be seen. This model can be used to study the pathogenesis of hypertrophic scars and keloids

　　and evaluate the efficacy. The advantage of this model is to study the whole process from wound healing to scar hyperplasia, and the research object is not separated from the original environment of its occurrence and development, and the experimental results are more objective. But its disadvantage is that whether the scars produced are hypertrophic scars and keloids is still very controversial; the degree of scar hyperplasia is far less obvious than that of human hypertrophic scars or keloids, and the duration is shorter; the success rate of the model is low.