Establishment of CTX Model Animal and Survey of its Pathogenesis.

脑腱黄瘤病（CTX）是一种以血清和各器官中胆固醇含量升高为特征的遗传性固醇储存病。为了阐明CTX的发病机制，用富含胆甾烷醇的饮食喂养小鼠。使用HPLC测定血清、肝脏和小脑中甾醇的浓度。(1)在胆甾烷醇喂养的小鼠中，血清和肝脏中的胆甾烷醇浓度在前2至4周达到最大值。此后胆甾烷醇浓度下降，最终降至最大值的50- 60%。另一方面，小脑中的胆甾烷醇水平几乎与进食时间平行地线性增加，并且没有观察到下降。这些结果表明，肝脏的能力，以消除或降解胆甾烷醇增加长期摄入这种化合物，而小脑没有这样的反馈调节。使用电子显微镜进行的组织学检查显示， 关于我们 胆固醇喂养小鼠肝脏中的溶酶体颗粒。(2)20%的小鼠出现两种类似于人类钙化带角膜病变的角膜混浊。电镜下可见上皮基底膜与间质之间有结晶颗粒。材料的能量色散分析，推测为胆甾烷醇。这些结果表明，胆甾烷醇可能由于血清水平升高而在角膜中存款。角膜及相关区域胆甾烷醇沉积可能是CTX致角膜营养不良的原因之一。(3)在喂食胆甾烷醇饲料14个月后，20%的小鼠出现了由55%胆固醇和45%胆甾烷醇组成的胆结石，并伴有胆囊粘膜炎症和浆膜血管增厚。实验数据表明，胆甾烷醇替代血清和肝脏中的胆固醇，导致胆甾烷醇生物合成增加，但抑制胆汁酸合成。这些现象的组合促进胆固醇喂养小鼠的胆石形成。这三个发现证明了该模型动物在研究CTX发病机制中的有用性。少

Cerebrotendinous xanthomatosis (CTX) is a hereditary sterol storage disease which is characterized by the increase in the cholestanol content in the serum and various organs. In order to elucidate the pathogenesis of CTX, mice were fed with a diet rich in cholestanol. The concentrations of sterol in the serum, liver, and cerebellum were determined using HPLC. (1) In the cholestanol-fed mice, the cholestanol concentrations in the serum and liver reached maxima in the first 2 to 4 weeks. Cholestanol concentration declined thereafter, finally to 50-60 % of the maxima. On the other hand, the levels of cholestanol in the cerebellum increased almost linearly in parallel to the feeding time, and no decline was observed. These results suggest that the capacity of the liver to remove or degrade cholestanol was increased by long-term intake of this compound, whereas the cerebellum had no such feed-back regulation. Histological examinations using an electron microscops revealed the enlargement of … More lysosomal granules in the liver of the cholestanol-fed mice. (2) Two kinds of corneal opacities resembling calcific band keratopathy in human were also found in 20 % of these cholestanolfed mice. The crystal particles were observed between epithelial basement membrane and superficial stroma by the electron microscopy. Energy dispersive analysis of the materials, which was presumed to be cholestanol. These results suggest that the cholestanol may deposit in the cornea from elevated serum levels. Deposition of cholestanol in cornea and related area may be a cause of corneal dystrophy in CTX. (3) After feeding cholestanol diet for 14 months, gallstones composed of 55 % cholesterol and 45 % cholestanol developed in 20 % of the mice and were associated with gallbladder mucosal inflammation and serosal vessel thickening. Experimental data demonstrate that cholestanol replaces cholesterol in serum and liver, causes increased cholestanol biosynthesis, but inhibits bile acid synthesis. The combination of these phenomena promotes gallstone formation in cholestanol-fed mice. These three findings proof the usefulness of this model animal in the investigation of CTX pathogenesis. Less