Saito Hikaru, Miyakoshi Naohisa, Kasukawa Yuji, Nozaka Koji, Tsuchie Hiroyuki, Sato Chiaki, Abe Kazunobu, Shoji Ryo, Shimada Yoichi
Department of Orthopedic Surgery, Akita University Graduate School of Medicine, 1-1-1, Hondo, Akita, 010-8543, Japan.
Osteoporos Sarcopenia. 2021 Dec;7(4):121-126. doi: 10.1016/j.afos.2021.11.001. Epub 2021 Nov 20.
The purpose of this study is to investigate the stage of chronic kidney disease (CKD) in adenine-induced CKD model rats by serum analyses, and to examine bone mineral density (BMD), bone strength, and microstructure of trabecular and cortical bone in these rats.
Eight-week-old, male Wistar rats (n = 42) were divided into 2 groups: those fed a 0.75% adenine diet for 4 weeks until 12 weeks of age to generate CKD model rats (CKD group); and sham rats. The CKD and sham groups were sacrificed at 12, 16, and 20 weeks of age (n = 7 in each group and at 12, 16, and 20 weeks), and various parameters were evaluated, including body weight, renal wet weight, muscle wet weight, renal histology, biochemical tests, BMD, biomechanical testing, and micro-computed tomography (CT). The parameters were compared between the 2 groups at the various time points.
In the CKD model rats, at 20 weeks of age, serum creatinine, phosphorus, and intact-PTH levels were elevated, and serum calcium levels were normal, indicating that the CKD was stage IV and associated with secondary hyperparathyroidism. Decreased BMDs of the whole body and the femur were observed as bone changes, and micro-CT analysis showed deterioration of bone microstructure of the cortical bone that resulted in decreased bone strength in the cortical and trabecular bone.
These CKD model rats showed stage IV CKD and appear appropriate for evaluating the effects of several treatments for CKD-related osteoporosis and mineral bone disorder.
本研究旨在通过血清分析调查腺嘌呤诱导的慢性肾脏病(CKD)模型大鼠的慢性肾脏病阶段,并检测这些大鼠的骨矿物质密度(BMD)、骨强度以及小梁骨和皮质骨的微观结构。
将8周龄雄性Wistar大鼠(n = 42)分为2组:一组喂食含0.75%腺嘌呤的饲料4周,直至12周龄以建立CKD模型大鼠(CKD组);另一组为假手术大鼠。CKD组和假手术组在12、16和20周龄时处死(每组在12、16和20周时各7只),并评估各种参数,包括体重、肾脏湿重、肌肉湿重、肾脏组织学、生化检测、BMD、生物力学测试和微型计算机断层扫描(CT)。在各个时间点比较两组之间的参数。
在CKD模型大鼠中,20周龄时血清肌酐、磷和完整甲状旁腺激素(PTH)水平升高,血清钙水平正常,表明CKD为IV期且伴有继发性甲状旁腺功能亢进。观察到全身和股骨的BMD降低,这是骨变化,微型CT分析显示皮质骨的骨微观结构恶化,导致皮质骨和小梁骨的骨强度降低。
这些CKD模型大鼠表现为IV期CKD,似乎适合评估几种治疗CKD相关骨质疏松症和矿物质骨疾病的效果。