Immunohistochemical observations on the initial disorders of the epiphyseal growth plate in the cause of Hyena disease.

牛鬣狗病被认为是一种骨骼生长紊乱，由于后肢的高度低于前肢，其外观类似于鬣狗的身材。我们已经明确表明，鬣狗病是由过量服用维生素A （VA）引起的。在本研究中，作为下一步，我们在给予高剂量VA.1的幼龄大鼠的骨骺生长板软骨局灶性消失过程中组织化学检查了随后的组织学紊乱。从出生后第4周开始，连续5天给予10万IU/100 g体重/天的VA，并于实验第12天和第19天处死。采用免疫组化方法检测胫骨I型、II型和X型胶原，凝集素组化方法检测胫骨螺旋体。提示骨骺生长板软骨基质异常钙化，呈骨基质样表型。骨骺生长层的侵蚀区可能是由破骨细胞侵入改变的软骨基质引起的，并可能在破骨细胞和成骨细胞的作用下，通过建模或重塑发展为局灶性消失。用离心培养法研究了VA代谢产物维甲酸（RA）从增生型软骨到肥厚型软骨的分化过程。结果表明，添加RA后，增生软骨基质减少。这些结果表明，VA大鼠骨骺生长板内发生了破骨细胞对钙化软骨基质的吸收和成骨细胞对骨组织的形成等模拟或重塑过程。这种建模或重塑可能会进一步进行，最终导致骺生长板的局灶性消失。

Bovine Hyena disease is regarded as a disorder of skeletal growth, with an appearance similar to a Hyena figure due to lower hind limbs than fore limbs in height. It has been definitely shown by us that Hyena disease is caused by excessive administration of vitamin A (VA). In the present study, as the next step, we examined the succeeding histological disorders in the process of the focal disappearance of the epiphyseal growth plate cartilage histochemically in young rats administered a high dose of VA.1. Animals were given 100,000 IU/100 g body weight/day of VA for 5 days from 4 weeks after birth and sacrificed on Day 12 and 19 of the experiment. Tibiae were examined by immunohistochemistry for type I, II and X collagens, and lectin-histochemistry for Helix pomatia. These findings suggested that the cartilage matrix of the epiphyseal growth plate was abnormally calcified and showed the phenotypes like bone matrix. The eroded regions of the epiphyseal growth plated seemed to be caused by the invasion of osteoclasts into the altered cartilage matrix and might develop to the focal disappearances by the modeling or remodeling due to action of osteoclasts and osteioblasts.2. A differential process from the proliferatic chondrocites to the hypertrofic chondrocites was examined in a retinoic acid (RA) of metabolic products of VA with the centrifugal culture methods. It was shown that decreases of the matrix of proliferatic chondrocites were occurred by addition of RA.These findings indicated that a modeling or remodeling process, such as the absorption of the calcified cartilage matrix by osteoclasts and the formation of bone tissues by osteoblasts, were occurred within the epihyseal growth plate in VA rats. Such a modeling or remodeling might further proceed, and finally bring about the focal disappearances of the epiphyseal growth plate.