Damei Li, Kang Xun, Miao Jia, Shaobo Sun, Qian Wu, Weijiang Wu, Donghua Jin
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引用次数: 0
Abstract
Introduction: Cognitive impairment (CI) is common in patients with end-stage renal disease (ESRD), but the mechanism of uremia-associated CI is poorly recognized.
Methods: In this study, we constructed uremia rat models, treated with high level phosphate (Pi) and vascular calcification inhibitor sodium thiosulphate (STP). Assessed the spatial learning and memory by Morris Water Maze (MWM), detected the vascular calcification (VC) by histological staining and monitored the osteogenic factors ALP and Runx2 expressions in Uremia + Pi and Uremia + Pi + STP rats through qPCR, Western blotting analysis and Immunohistochemistry analysis. Moreover, we examined the calcium content, and the ALP and Runx2 expressions in VSMCs treated with Pi and STP.
Results: The results showed that both the learning and memory abilities and the spatial exploration ability of the rats in Uremia + Pi group were significantly decreased with enhanced expressions of ALP and Runx2, calcium content and ALP activity, however, STP supplementation significantly alleviated the spatial learning and memory damage, reduced the ALP and Runx2 expressions, calcium content and ALP activity. Moreover, Pi treatment significantly increased the calcium and MDA content in VSMCs, and ALP and Runx2 expressions, STP addition reversed these changes, indicating high phosphate level induced VC development.
Conclusion: Taking together, these results indicated that elevated serum phosphate might promote VC in uremic rats by activating the expressions of ALP and Runx2, thereby causing damages to the kidneys and complications of uremia such as CI. Therefore, this study improved understanding to possible pathogenic mechanisms of uremia-induced CI, and will be beneficial to optimize the prevention and treatment strategy for CI in uremia patients.
期刊介绍:
This journal comprises both clinical and basic studies at the interface of nephrology, hypertension and cardiovascular research. The topics to be covered include the structural organization and biochemistry of the normal and diseased kidney, the molecular biology of transporters, the physiology and pathophysiology of glomerular filtration and tubular transport, endothelial and vascular smooth muscle cell function and blood pressure control, as well as water, electrolyte and mineral metabolism. Also discussed are the (patho)physiology and (patho) biochemistry of renal hormones, the molecular biology, genetics and clinical course of renal disease and hypertension, the renal elimination, action and clinical use of drugs, as well as dialysis and transplantation. Featuring peer-reviewed original papers, editorials translating basic science into patient-oriented research and disease, in depth reviews, and regular special topic sections, ''Kidney & Blood Pressure Research'' is an important source of information for researchers in nephrology and cardiovascular medicine.