原发性甲状旁腺功能亢进动物模型的建立

Establishment of Animal Model with Primary Hyperparathyroidism

目的 建立一种适合于影像学对照研究的原发性甲状旁腺功能亢进动物模型。方法 将 80只成年白兔随机分为 8组 ,每组 10只。并设对照组 3 0只以正常饮食 (Ca∶P =1∶0 .7)喂养。实验组 5 0只以高磷饮食 (Ca∶P =1∶7)喂养。分别在喂养前一周及喂养后第 1、2、3、4、5个月末对所有动物做血钙、血磷、血PTH测定 ,并进行骨影像学及喂养后动物的甲状旁腺、肾及其骨骼病理学观察。结果 整个实验过程中 ,实验组血PTH水平明显高于对照组。在前 3个月时 ,血钙水平下降 ,而血磷水平变化无明显差异 ,在第 4、5个月末 ,血钙水平明显升高 ,而血磷水平明显下降。甲状旁腺组织学检查 :在 1个月时无变化 ,2个月时实验组 10例中 6例显示轻度增生 ,3个月时 10例中 9例显示轻、中度增生。在第 4、5个月末 ,2 0例均明显增生。影像学检查 :前 3个月骨骼影像学检查未发现异常改变 ,第 4个月末 ,10例有 7例肋骨、骶骨及髂骨密度降低。第 5个月末 ,10例均显示肋骨、骶骨及髂骨骨密度减低及骨膜下骨皮质吸收 ,而对照组中所有动物未发现异常病理变化。结论 高磷饮食可成功地建立适合影像学研究的原发性甲状旁腺功能亢进动物模型。

Objective To establish a rabbit model of primary hyperparathyroidism (PHPT) for imaging study. Methods Eighty rabbits were divided into eight groups of 10 each.Thirty rabbits were fed a control diet (Ca∶P=1∶0.7) and 50 rabbits were fed a high phosphate diet (Ca∶P=1∶7) for 1-, 2-, 3-, 4-, 5-month intervals. Compared with the control animals, serum PTH levels, serum calcium levels and serum phosphorus levels were determined.The imaging study of skeleton and pathological examination of the parathyroid and kidney were performed in these rabbits regularly. Results Compared with the control animals, serum PTH levels were elevated at all five time intervals in experimental group, whereas serum calcium levels were decreased in three months, but serum phosphorus levels did not change. Serum calcium levels were increased after three months, but serum phosphorus levels were decreased. Parathyroid histopathologic studies demonstrated no change at 1 month whereas six of ten experimental animals showed mild hyperplasia at 2 months and nine of ten showed mild to moderate hyperplasia at 3 months, but all of 20 showed mild to moderate hyperplasia with gland enlargement compared with control animal at 4 and 5 months. The skeletal imaging changes of all rabbits were not remarkable at 3 months, but the increased cortical bone resorption produced increased porosity in experimental groups after 3 months. Seven of ten showed decreased density of the costal bone, the sacrum and ilum at 4 months and all of ten showed decreased density, osteoporosis and cortical bone resorption of the costal bone,the sacrum and ilum at 5 months. The skeletal imaging study and pathological examination of the control groups were not change at all time intervals. With this model it was convenient to perform the imaging study of osteopathy in primary hyperparathyroidism. Histopathologic examination of the kidneys showed no change at 1 month but focal parenchymal inflammation with calcium deposition at 2-,3-,4-,5-month in the experimental groups. Conclusion Animal model with primary hyperparathyroidism can be established by high-phosphate diet.