School of Life Sciences, Thomson Building, University of Glasgow, University Avenue, Glasgow G12 8QQ, U.K.
Institute of Cardiovascular and Medical Sciences, University of Glasgow, University Avenue, Glasgow G12 8QQ, U.K.
Clin Sci (Lond). 2018 Jun 26;132(12):1315-1328. doi: 10.1042/CS20171572. Print 2018 Jun 29.
The effect of salt on cerebral small vessel disease (SVD) is poorly understood. We assessed the effect of dietary salt on cerebral tissue of the stroke-prone spontaneously hypertensive rat (SHRSP) - a relevant model of sporadic SVD - at both the gene and protein level. Methods Brains from 21-week-old SHRSP and Wistar-Kyoto rats, half additionally salt-loaded (via a 3-week regime of 1% NaCl in drinking water), were split into two hemispheres and sectioned coronally - one hemisphere for mRNA microarray and qRT-PCR, the other for immunohistochemistry using a panel of antibodies targeting components of the neurovascular unit. Results We observed differences in gene and protein expression affecting the acute phase pathway and oxidative stress ( and , up-regulated in salt-loaded WKY versus WKY, >2-fold), active microglia (increased Iba-1 protein expression in salt-loaded SHRSP versus salt-loaded WKY, p<0.05), vascular structure ( and , up-regulated in salt-loaded SHRSP versus SHRSP, >3-fold; and down-regulated >2-fold in salt-loaded SHRSP versus SHRSP) and myelin integrity ( down-regulated in salt loaded WKY rats versus WKY, >2.5-fold). Changes of salt-loading were more pronounced in SHRSP and occurred without an increase in blood pressure in WKY rats.
Salt exposure induced changes in gene and protein expression in an experimental model of SVD and its parent rat strain in multiple pathways involving components of the glio-vascular unit. Further studies in pertinent experimental models at different ages would help clarify the short- and long-term effect of dietary salt in SVD.
盐对脑小血管病(SVD)的影响知之甚少。我们评估了饮食盐对易卒中型自发性高血压大鼠(SHRSP)脑组织的影响 - 一种散发性 SVD 的相关模型 - 在基因和蛋白水平上。方法:21 周龄 SHRSP 和 Wistar-Kyoto 大鼠的大脑被分为两个半球并冠状切片 - 一个半球用于 mRNA 微阵列和 qRT-PCR,另一个用于免疫组织化学,使用针对神经血管单元成分的抗体面板。结果:我们观察到影响急性期途径和氧化应激的基因和蛋白表达差异( 和 ,在盐负荷 WKY 中上调,WKY 上调 2 倍以上),活性小胶质细胞(盐负荷 SHRSP 中 Iba-1 蛋白表达增加,盐负荷 SHRSP 中上调 >2 倍,p<0.05),血管结构( 和 ,在盐负荷 SHRSP 中上调 >3 倍;和 ,盐负荷 SHRSP 中下调 >2 倍)和髓鞘完整性(盐负荷 WKY 大鼠中下调 >2.5 倍,WKY)。盐负荷的变化在 SHRSP 中更为明显,而在 WKY 大鼠中血压没有增加。结论:盐暴露在 SVD 及其亲本大鼠的多个途径中诱导了基因和蛋白表达的变化,涉及胶质血管单元的成分。在不同年龄的相关实验模型中进行进一步研究将有助于阐明饮食盐在 SVD 中的短期和长期影响。