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目的建立食蟹猴铁过载模型,监测模型动物血清转铁蛋白饱和度水平,通过对心脏、肝脏、脾脏、肾脏、胰腺、胸骨骨髓、淋巴结(腹股沟淋巴结、腋下淋巴结、颌下淋巴结和肠系膜淋巴结)进行普鲁士蓝铁染色,确定食蟹猴铁过载模型铁离子蓄积部位。方法 4只健康食蟹猴,雌雄各半,年龄3岁,体重2～3 kg,每周腹腔注射右旋糖酐铁注射液1次,给药剂量为200 mg·kg-1,连续给药5次。给药前收集1次血样,末次给药后每周收集1次血样,采用全自动生化分析仪对血清转铁蛋白饱和度进行检查,以转铁蛋白饱和度>75%并维持8周作为模型建立标志。建模前,模型建立后d 1,d 14,d 28,d 56分别收集血样,d 117,d 142收集2只雄性食蟹猴血样,监测模型动物血清转铁蛋白饱和度水平。模型建立后d 142将2只雄性食蟹猴进行安乐死,对心脏、肝脏、脾脏、肾脏、胰腺、胸骨骨髓、淋巴结(腹股沟淋巴结、腋下淋巴结、颌下淋巴结和肠系膜淋巴结)进行普鲁士蓝铁染色。结果经5次腹腔注射右旋糖酐铁,4只食蟹猴血清转铁蛋白饱和度水平均>75%并可维持8周,按照上述方法已成功建立食蟹猴铁过载模型。建模前,模型建立后d 1,d 14,d 28,d 56,d 117,d 142雄性动物血清转铁蛋白饱和度(%)分别为:♂1(45.88,90.05,92.70,90.96,91.72,93.66,93.61),♂2(42.71,91.96,93.01,77.95,92.46,93.89,92.65),d 1,d 14,d 28,d 56雌性动物血清转铁蛋白饱和度(%)分别为:♀1(47.91,90.81,72.75,50.02,40.15),♀2(40.93,83.58,45.68,37.92,40.77)。2只雌性食蟹猴血清转铁蛋白饱和度在模型建立后d 14均出现较大程度降低,至d 56时已明显低于75%的判断标准,同期2只雄性食蟹猴该指标与模型建立成功时相比较除1只猴1个时间点外未见明显变化,至d 142仍可维持在>90%水平,该结果提示雌性食蟹猴不适合用于建立铁过载模型。普鲁士蓝铁染色结果显示铁离子主要蓄积于肝脏、脾脏红髓、淋巴结(腹股沟淋巴结、腋下淋巴结、颌下淋巴结和肠系膜淋巴结)、胸骨骨髓内,肾脏、肾上腺及肺脏等器官也可见部分蓄积。结论建立了雄性食蟹猴铁过载模型,至模型建立后d 142仍稳定铁过载,血清转铁蛋白饱和度水平>90%。食蟹猴铁过载模型动物铁离子主要蓄积部位为肝脏、脾脏红髓、淋巴结及胸骨骨髓。
Objective To establish a model of iron overload in cynomolgus monkeys and monitor the level of serum transferrin saturation in the model animals. The levels of serum transferrin saturation in heart, liver, spleen, kidney, pancreas, sternum bone marrow, lymph nodes (inguinal lymph nodes, axillary lymph nodes, submandibular lymph nodes and mesenteric lymph nodes ) Prussian blue-iron staining to determine cynomolgus iron overload model iron ion accumulation sites. Methods Four healthy cynomolgus monkeys, aged 3 years old and weighing 2 to 3 kg, were injected intraperitoneally with iron dextran injection once a day for 200 mg · kg-1 at a dose of 5 mg. Blood samples were collected 1 time before administration and once a week after the last administration. Serum transferrin saturation was examined using an automated biochemical analyzer, with transferrin saturation> 75% and maintenance for 8 weeks Create logo. Before modeling, blood samples were collected on d 1, d 14, d 28 and d 56, respectively, and two male cynomolgus monkeys blood samples were collected at d 117 and d 142 to monitor the serum transferrin saturation of the model animals. Two male cynomolgus monkeys were euthanized with Prussian blue iron staining of heart, liver, spleen, kidney, pancreas, sternal bone marrow, lymph nodes (inguinal lymph nodes, axillary lymph nodes, submandibular lymph nodes and mesenteric lymph nodes) . Results After five intraperitoneal injections of iron dextran, all four cynomolgus monkeys serum transferrin saturation levels were> 75% and can be maintained for 8 weeks, according to the above method has been successfully established cynomolgus iron overload model. Before model establishment, the serum transferrin saturation (%) of males at d 1, d 14, d 28, d 56, d 117 and d 142 after establishment of model were respectively ♂1 (45.88,90.05,92.70,90.96,91.72 , 93.66,93.61), ♂2 (42.71,91.96,93.01,77.95,92.46,93.89,92.65), d 1, d 14, d 28, d 56 females serum transferrin saturation (%) were: ♀ 1 (47.91,90.81,72.75,50.02,40.15), ♀2 (40.93,83.58,45.68,37.92,40.77). Serum transferrin saturation of two female cynomolgus monkeys decreased significantly on day 14 after establishment of the model, and was significantly lower than 75% on day d 56. The index and model of two male cynomolgus monkeys There was no significant change at 1 establishment point compared with 1 monkey at the time of successful establishment, and the level of d 142 remained at> 90%. This result suggests that female cynomolgus monkey is not suitable for establishing iron overload model. The results of Prussian blue staining showed that the accumulation of iron ions was mainly found in the liver, spleen, red pulp, lymph nodes (inguinal lymph nodes, axillary lymph nodes, submandibular lymph nodes and mesenteric lymph nodes), sternal bone marrow, kidney, adrenal glands and lungs. Conclusion The iron overload model of male cynomolgus monkey was established. After the model was established, the iron overload was stable at d 142, and the level of serum transferrin saturation was> 90%. Cynomolgus iron overload model animal iron ions mainly accumulate parts of the liver, spleen red marrow, lymph nodes and sternal bone marrow.