Female cotton rats (Sigmodon hispidus) develop chronic anemia with renal inflammation and cystic changes
Female cotton rats (Sigmodon hispidus) develop chronic anemia with renal inflammation and cystic changes
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DOI：
10.1007/s00418-016-1438-3
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发表时间：
2016-09-01
影响因子：
2.3
通讯作者：
Kon, Yasuhiro
中科院分区：
文献类型：
--
作者：
Ichii, Osamu;Nakamura, Teppei;Kon, Yasuhiro
棉鼠（Sigmodon hispidus）是一种实验室啮齿动物，已被用于研究人类传染病。在本研究中，我们观察到雌性棉花大鼠，而不是雄性棉花大鼠，在5 - 9月龄时发生慢性贫血，其特征是红细胞、血红蛋白和红细胞压积水平降低，而平均红细胞血红蛋白和体积水平没有任何变化。在外周血中，雌性棉花大鼠的网织红细胞计数未因贫血而增加，肝脏和脾脏也未见髓外造血。此外，与雄性棉花大鼠相比，雌性棉花大鼠的血清尿素氮和肌酐水平在5 - 9月龄时升高，并且在10月龄后这些升高变得更加明显，表明慢性肾脏疾病。在组织学上，雌性棉花大鼠在5 ~ 9月龄时表现为小管间质病变，主要表现为单个核细胞（包括浆细胞和CD3(+) t细胞）浸润，以及calbinin - d28k（+）远端小管扩张。这些病变的严重程度从10月龄开始逐渐加重，肾纤维化特征和大量小管囊肿出现，但没有明显的肾小球病变。老龄雌性棉大鼠肾脏促红细胞生成素水平明显降低，贫血与小管间质损伤有显著相关性。这些结果提示老年雌性棉花大鼠慢性发生肾性贫血，这种啮齿动物可能作为阐明其发病机制的新模型。
The cotton rat (Sigmodon hispidus) is a laboratory rodent that has been used for studies on human infectious diseases. In the present study, we observed that female cotton rats, not the male cotton rats, developed chronic anemia characterized by reduced red blood cell, hemoglobin, and hematocrit levels from 5 to 9 months of age without any changes in the mean corpuscular hemoglobin and volume levels. In peripheral blood, the reticulocyte count did not increase in response to anemia in female cotton rats, and no extramedullary hematopoiesis was observed in the liver or spleen. Further, the serum levels of urea nitrogen and creatinine increased from 5 to 9 months of age in female cotton rats compared to male cotton rats, and these increases became more prominent from 10 months of age onward, indicating chronic kidney disease. Histopathologically, female cotton rats manifested tubulointerstitial lesions characterized by the infiltration of mononuclear cells, including plasma cells and CD3(+) T-cells, as well as the dilation of calbindin-D28k(+) distal tubules from 5 to 9 months of age. The severity of these lesions progressed from 10 months of age onward, and renal fibrotic features and numerous tubular cysts appeared without any obvious glomerular lesions. A significant decrease in the erythropoietin protein levels was observed in the kidney of aged female cotton rats, and significant correlations were detected between anemia and tubulointerstitial damage. These results suggest that aged female cotton rats chronically develop renal anemia, and this rodent may serve as a novel model to elucidate its pathogenesis.