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腺嘌呤和高磷饮食诱导的 CKD 大鼠模型中伴有骨异常的 SHPT。

A rat model of SHPT with bone abnormalities in CKD induced by adenine and a high phosphorus diet.

机构信息

Institute of Nephrology, Zhongda Hospital, Southeast University School of Medicine, Nanjing, Jiangsu, 210009, China.

Biomechanics Laboratory, School of Biological Science and Medical Engineering, Southeast University, Nanjing, Jiangsu 210096, China.

出版信息

Biochem Biophys Res Commun. 2018 Apr 6;498(3):654-659. doi: 10.1016/j.bbrc.2018.03.038. Epub 2018 Mar 16.

Abstract

The study of parathyroid hyperplasia with bone disease as a critical manifestation of chronic kidney disease-mineral and bone disorders (CKD-MBDs) is challenging due to the lack of a suitable research model. Here, we established a rat model with secondary hyperparathyroidism (SHPT) and bone disease induced by adenine and a high phosphorous diet and analyzed the skeletal characteristics. We performed blood analysis, emission computed tomography (ECT), dual energy X-ray absorptiometry (DEXA), micro-computed tomography (micro-CT), bone histomorphometry, and bone mechanical tests. The CKD rats with SHPT induced by adenine and a high phosphorus diet showed severe abnormalities in calcium and phosphorus metabolism and exhibited parathyroid hyperplasia. The bone mineral density (BMD) of femurs and lumbar vertebrae was significantly lower in the CKD rats than in the control (CTL) rats. The cortical and trabecular bone parameters of femurs showed significant bone loss. In addition, we found decreases in ultimate force, work to failure, stiffness, and elastic modulus in the CKD rats. In conclusion, our findings demonstrated that the CKD rats with SHPT induced by adenine and a high phosphorus diet may serve as a useful model for skeletal analysis in CKD with SHPT.

摘要

甲状旁腺增生的研究,尤其是作为慢性肾脏病-矿物质和骨异常(CKD-MBDs)的一个关键表现,具有挑战性,因为缺乏合适的研究模型。在这里,我们建立了一个由腺嘌呤和高磷饮食诱导的继发性甲状旁腺功能亢进症(SHPT)和骨疾病的大鼠模型,并分析了其骨骼特征。我们进行了血液分析、发射型计算机断层扫描(ECT)、双能 X 射线吸收仪(DEXA)、微计算机断层扫描(micro-CT)、骨组织形态计量学和骨力学测试。由腺嘌呤和高磷饮食诱导的 CKD 大鼠出现严重的钙磷代谢异常,并伴有甲状旁腺增生。与对照组(CTL)大鼠相比,CKD 大鼠的股骨和腰椎骨矿物质密度(BMD)显著降低。股骨的皮质和小梁骨参数显示出明显的骨丢失。此外,我们发现 CKD 大鼠的最终力、破坏功、刚度和弹性模量降低。总之,我们的研究结果表明,由腺嘌呤和高磷饮食诱导的 CKD 大鼠伴有 SHPT,可能成为 CKD 伴有 SHPT 的骨骼分析的有用模型。

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