动物造模,药效评价,干眼模型 z-bio 2024-08-07 348

　　1. New Zealand black/white (NZB/NZW) F1 hybrid mice obtained by hybridization technology can produce significant autoimmune reactions in their lacrimal gland tissue with age, exhibiting changes similar to Sj ö gren's syndrome.

　　Liu et al. extracted homogenate from one lacrimal gland of Lewis mice, added inactivated pertussis bacilli to the homogenate lacrimal gland tissue for further treatment, and then injected it back into the opposite lacrimal gland to enhance its antigenicity, induce more severe autoimmune reactions in the lacrimal and salivary glands, and create a Sj ö gren syndrome dry eye model.

　　3. Primary Sj ö gren syndrome model can be obtained by removing the thymus of NFS/sld mutant mice obtained through gene mutation technology 3 days after birth. In the serum of Sj ö gren syndrome patients, researchers have discovered a series of autoantibodies, such as SS-A and SS-B antibodies, 120 kDa a-fodrin antibodies, M1 Ach antibodies, and M3 Ach antibodies. NFs/sld mice with thymus removed at 3 days of birth have been used to confirm the presence of 120 kDa a-fodrin self antigen, which is considered the main factor in salivary gland damage in Sj6gren's syndrome. It is a product of 240 kDa a-fodrin cleaved by caspase3 and can be purified from the salivary glands of 3d Tx NFs/sld mice. Therefore, this model is an ideal model for studying the mechanism of cell apoptosis in Sj ö gren syndrome. However, due to the various negative effects of thymectomy on endocrine function in the body, the application of this model as a long-term research model is limited.

　　IQI/Jic mice are a new dry eye model, and their lymphocyte infiltration is limited to the lacrimal and salivary glands, making them a good model for studying early dry eye. Konno et al. speculated that in the early stages of inflammation, it may be mediated by dendritic cells or lacrimal gland epithelial cells, which also function as secondary antigen-presenting cells. But after 9 months, it will develop into severe lacrimal gland inflammation, which makes its research cost higher.

　　5. Establishment of a castrated female mouse dry eye model, specific preparation method: intraperitoneal injection of 3.3ml/kg chloral hydrate anesthesia, with the abdomen lying on the mouse rack. Hair removal is performed in the surgical area of the lower back by approximately 2cm x 2cm, with 1cm below the last rib. The skin is incised along the spine, and the muscles are separated to enter the abdominal cavity. Completely remove the pink ovary slightly smaller than a soybean below the kidney, observe no bleeding at the incision site, and then suture the muscle and skin layer by layer. Resection of the contralateral ovary using the same method. The control group incised the skin according to the above method, separated the muscles and entered the abdominal cavity. After finding the ovaries, they were not removed, and the muscles and skin were sutured layer by layer. After surgery, erythromycin eye ointment was applied to the incision to prevent infection. Suture was removed 6 days after surgery, and the incision healed in one stage.

　　The pathogenesis of dry eye caused by estrogen deficiency is not yet fully understood. Currently, it is believed that the ocular surface components (cornea, conjunctiva, accessory lacrimal gland, meibomian gland), the main lacrimal gland, and their neural innervation form a complete functional unit. If one of the parts is damaged, the tear film used to maintain normal ocular surface is also affected, leading to immune based inflammatory reactions and damaging the normal function of the lacrimal gland and its nerves. Wickham et al. believe that estrogen receptors are expressed in the lacrimal gland, glandular epithelium, meibomian gland, eyelids, conjunctiva, and cornea. Azzarolo et al. reported that estrogen plays an important role in maintaining the structure and function of the lacrimal gland, and a decrease in estrogen levels may trigger apoptosis and necrosis of lacrimal gland cells, as well as lymphocyte infiltration.