Experimental Reproduction of itai-itai disease in cynomolgus monkeys

食蟹猴痛痛病的实验复制

• 批准号: 10460136
• 负责人: UMEMURA Takashi
• 金额: $ 9.6万
• 依托单位: HOKKAIDO UNIVERSITY
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B).
• 财政年份: 1998
• 资助国家: 日本
• 起止时间: 1998 至 2000
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-10460136/
• 关键词: Itai-itai disease; Cadmium toxicosis; Osteomalacia; Cadmium osteopathy; Tubular nephrosis; Nephrogenic anemia; Cynomolgus monkey; エストロゲン; カドミウム中毒; カニクイザル; 慢性中毒症; カドミウム腎症

Itai-Itai means ouch-ouch in English, and human patients affected with the Itai-Itai disease (IID) complain of severe and continuous pain caused by spontaneous, multiple fractures of bones. IID occurs mainly in post-menopausal women and characteristic pathological findings of the disease are tubular nephropathy, osteomalacia and renal anemia. Many workers have tried to reproduce the bone lesion and renal anemia by Cd intoxication using various animals, but few of them succeeded in producing osteomalacia. Renal anemia has not been observed in Cd-treated animals. Because of the difficulties in the experimental reproduction of the lesions distinctive of IID by Cd treatment, some researchers insist that the real cause of IID is not Cd toxicosis, but malnutrition or vitamin D deficiency. Paucity of animal model of IID has also impeded the better understanding of the pathogenesis of tubular nephropathy, renal anemia and osteomalacia of IID, development of novel treatment for the disease, and establish more reasonable criteria for the diagnosis of the disease.In the present our experiment, ten, ovariectomized cynomolgus monkeys were given intravenous injections of 0, 1.0 or 2.5 mg/kg Cd, 2 or 3 days per week, for 13 to 15 months. Normocytic normochromic anemia, renal lesions characterized by tubular atrophy and interstitial fibrosis (Cd nephropathy) and bone lesions characterized by the increase of osteoid and osteopenia (Cd osteopathy) were induced in the monkeys treated with Cd.Our experiment demonstrated that the chronic cadmium toxicosis similar to IID of humans is reproducible in monkeys by repeated intravenous injection of Cd. Using these animal models, we are now developing novel therapy for IID.

Itai-Itai在英语中的意思是哎哟，患有Itai-Itai病（IID）的人类患者抱怨由自发的多处骨折引起的严重和持续的疼痛。IID主要发生于绝经后妇女，其特征性病理表现为肾小管性肾病、骨软化和肾性贫血。许多工作者试图用各种动物复制镉中毒引起的骨损伤和肾性贫血，但很少有人成功地复制骨软化。在镉处理的动物中未观察到肾性贫血。由于实验重现镉处理引起的IID特征性病变的困难，一些研究者坚持认为IID的真实的原因不是镉中毒，而是营养不良或维生素D缺乏。本实验选用10只去卵巢的食蟹猴，分别静脉注射0、1.0和2.5mg/kg Cd，1.0 mg每周2或3天，持续13至15个月。正常红细胞正染性贫血，肾小管萎缩和间质纤维化（镉肾病）和骨质疏松（镉骨病）的特点是增加的类骨质和骨质减少（镉骨病变的特点是在猴子与镉治疗。我们的实验表明，慢性镉中毒类似于人类IID是重复静脉注射镉在猴子。利用这些动物模型，我们现在正在开发IID的新疗法。

项目成果

Kurata Y., Katsuta, O., Hiratsuka, H., Tsuchitani, M.and Umemura, T.: "Intravenous 1α, 25 [OH]_2 vitamin D_3 (calcitriol) pulse therapy for bone lesions in a murine model of chronic cadmium toxicosis"International Journal of Experimental Pathology. 81. 1-

Kurata Y.、Katsuta, O.、Hiratsuka, H.、Tsuchitani, M. 和 Umemura, T.：“静脉注射 1α, 25 [OH]_2 维生素 D_3（骨化三醇）脉冲疗法治疗慢性镉小鼠模型中的骨病变中毒》《国际实验病理学杂志》。81. 1-

Umemura, T.: "Experimental reproduction of itai-itai disease, a chronic cadmium poisoning of humans, in rats and monkeys"Japanese Journal of Veterinary Research. 48. 15-28 (2000)

Umemura, T.：“痛痛病（一种人类慢性镉中毒）在大鼠和猴子身上的实验再现”《日本兽医研究杂志》。

Umemura, T., Hiratsuka, H., Katsuta, O.and Tsuchitani, M.: "Intravenous administration of cadmium induces foam cell-emboli in the intrapulmonary veins of rats"Report of Environmental Pollution, and Reservation of Health. 63. 6-8 (1999)

Umemura, T.、Hiratsuka, H.、Katsuta, O. 和 Tsuchitani, M.：“静脉注射镉会在大鼠肺内静脉中诱导泡沫细胞栓塞”环境污染与健康保留报告。

Takashi Umemura: "Experimental reproduction of itai-itai disease, a chronic cadmium poisoning of humans, in rats and monkeys"Jpn. J. Vet. Res.. (in press). (2000)

Takashi Umemura：“痛痛病（一种人类慢性镉中毒）在大鼠和猴子身上的实验再现”Jpn。

Kurata Y.: "Intravenous lα, 25 [OH] 2 Vitamin D3 (calcitriol) pulse therapy for bone lesions in a murine model of chronic cadmium toxicosis"International Journal of Experimental Pathology. 81. 1-12 (2001)

Kurata Y.：“静脉注射lα，25 [OH] 2 维生素D3（骨化三醇）冲击治疗慢性镉中毒小鼠模型中的骨损伤”国际实验病理学杂志81. 1-12 (2001)。