High serum phosphate promotes cognitive impairment in uremia rats via mediating vascular calcification.

IF 2.1 4区 医学 Q2 PERIPHERAL VASCULAR DISEASE
Damei Li, Kang Xun, Miao Jia, Shaobo Sun, Qian Wu, Weijiang Wu, Donghua Jin
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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.

高血清磷酸盐通过介导血管钙化促进尿毒症大鼠认知功能障碍。
导读:认知障碍(CI)在终末期肾病(ESRD)患者中很常见,但尿毒症相关CI的机制尚不清楚。方法:建立尿毒症大鼠模型,采用高水平磷酸(Pi)和血管钙化抑制剂硫代硫酸钠(STP)处理。Morris水迷宫法(MWM)评估尿毒症+ Pi和尿毒症+ Pi + STP大鼠的空间学习记忆能力,组织染色法检测血管钙化(VC), qPCR、Western blotting和免疫组化法检测成骨因子ALP和Runx2的表达。此外,我们还检测了Pi和STP处理的VSMCs中钙含量、ALP和Runx2的表达。结果:尿毒症+ Pi组大鼠的学习记忆能力和空间探索能力均明显下降,ALP和Runx2的表达、钙含量和ALP活性均增强,而STP的补充可显著缓解空间学习记忆损伤,降低ALP和Runx2的表达、钙含量和ALP活性。此外,Pi处理显著提高了VSMCs中钙和MDA的含量,ALP和Runx2的表达,添加STP逆转了这些变化,表明高磷酸盐水平诱导了VC的发育。结论:综上所述,血清磷酸盐升高可能通过激活ALP和Runx2的表达来促进尿毒症大鼠VC,从而引起肾脏损伤和尿毒症并发症如CI。因此,本研究提高了对尿毒症致CI可能致病机制的认识,有利于优化尿毒症患者CI的防治策略。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
Kidney & blood pressure research
Kidney & blood pressure research 医学-泌尿学与肾脏学
CiteScore
4.80
自引率
3.60%
发文量
61
审稿时长
6-12 weeks
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.
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