Somers K L, Brown D E, Fulton R, Schultheiss P C, Hamar D, Smith M O, Allison R, Connally H E, Just C, Mitchell T W, Wenger D A, Thrall M A
Department of Pathology, Colorado State University, Fort Collins 80523, USA.
J Inherit Metab Dis. 2001 Aug;24(4):427-36. doi: 10.1023/a:1010588112003.
A feline model of Niemann-Pick disease type C (NPC) was employed to evaluate the effect of dietary cholesterol restriction on progression of disease. Two NPC-affected treated cats were fed a cholesterol-restricted diet beginning at 8 weeks of age; the cats remained on the diet for 150 and 270 days respectively. The study goal was to lower the amount of low density lipoprotein (LDL) available to cells, hypothetically reducing subsequent lysosomal accumulation of unesterified cholesterol and other lipids. Neurological progression of disease was not altered and dietary cholesterol restriction did not significantly decrease storage in NPC-affected treated cats. One NPC-affected treated cat had decreased serum alkaline phosphatase activity (ALP) and decreased serum cholesterol concentration. Liver lipid concentrations of unesterified cholesterol, cholesterol ester and phospholipids in NPC-affected treated cats were similar to those seen in NPC-affected untreated cats. Ganglioside concentrations in the NPC-affected treated cats and NPC-affected untreated cats were similar. Histological findings in liver sections from NPC-affected treated cats showed a diffuse uniform microvacuolar pattern within hepatocytes and Kupffer cells, in contrast to a heterogeneous macro/microvacuolar pattern and prominent nodular fibrosis in NPC-affected untreated cats. Similar differences in vacuolar patterns were seen in splenic macrophages. Although some hepatic parameters were modified, dietary cholesterol restriction did not appear to alter disease progression in NPC-affected kittens.
采用尼曼-匹克病C型（NPC）猫模型评估饮食中胆固醇限制对疾病进展的影响。两只患NPC的受试猫从8周龄开始喂食胆固醇限制饮食；这两只猫分别持续食用该饮食150天和270天。研究目的是降低细胞可利用的低密度脂蛋白（LDL）量，假设减少随后未酯化胆固醇和其他脂质在溶酶体中的蓄积。疾病的神经学进展未改变，饮食中胆固醇限制并未显著降低患NPC的受试猫的蓄积量。一只患NPC的受试猫血清碱性磷酸酶活性（ALP）降低，血清胆固醇浓度降低。患NPC的受试猫肝脏中未酯化胆固醇、胆固醇酯和磷脂的脂质浓度与未接受治疗的患NPC猫相似。患NPC的受试猫和未接受治疗的患NPC猫的神经节苷脂浓度相似。患NPC的受试猫肝脏切片的组织学结果显示，肝细胞和库普弗细胞内呈弥漫性均匀微泡状模式，而未接受治疗的患NPC猫则呈异质性大/微泡状模式和明显的结节性纤维化。脾巨噬细胞中也观察到类似的泡状模式差异。尽管一些肝脏参数有所改变，但饮食中胆固醇限制似乎并未改变患NPC小猫的疾病进展。
