Objective:The present study examines whether a long-term high salt diet causes hypertension and renal injury in normal subjects [Sprague-Dawley(SD) rats] and alters renal cytokine-related gene expression profiles.Meth...Objective:The present study examines whether a long-term high salt diet causes hypertension and renal injury in normal subjects [Sprague-Dawley(SD) rats] and alters renal cytokine-related gene expression profiles.Methods: Four 10 week old male SD rats received a high salt diet(HS,8%) and the other 4 SD rats received a normal salt diet(NS,0.5 %) for 8 weeks.Mean arterial pressure(MAP) and renal damages such as albuminuria and histological renal injury were determined.The relative mRNA levels of 514 cytokine-related genes(normalized by β-actin) in rat kidneys following NS or HS were determined quantitatively through analysis of 4 sets of gene expression profiles using the mouse cDNA membrane microarrays.Results: We demonstrated that 8 weeks of HS diet increased MAP [(140.0±5.3) vs(112.0±2.2) mmHg;1 mmHg=0.133 kPa,P<0.01],albuminuria [(41.4±3.2) vs(20.1±4.5) mg/d;P<0.01],and caused histological renal injury in SD rats,compared to NS group.Of the 514 genes in the array,there were 27(5.25%) genes with significantly different expression in the kidney of SD rats with HS compared to those of SD rats with NS.Functional clustering analysis indicated the following functional pathways related to high salt diet-induced hypertension:(1) pro-inflammatory response(↑IL-17,CCL28;↓NFκbib);(2) endothelial dysfunction(↓VEGF-A,VEGF-B,endoglin);(3) pro-matrix formation(↑osteopontin,IGFBP-5;↓IFN-γ);and(4) attenuated cell survival and differentiation(↓CNTF,IGF-Ⅱ R,ephrin-B1).Northern blot confirmed that 8 weeks of HS diet significantly decreased renal expression of VEGF mRNA,compared to NS group(P<0.01).ELISA showed that HS diet significantly decreased renal protein levels of VEGF and CCL28.Conclusion: These findings support the hypothesis that hypertension can be induced in normal rats by a long-term high salt diet,which is associated with increased renal injury and marked changes in renal cytokine gene expression profiles that are closely related to the pro-inflammatory response,pro-matrix formation,endothelial dysfunction,and attenuated cell survival and differentiation.展开更多
基金Supported by NIH/National Heart,Lung,and Blood Institute Grant(HL-51971)NIH/National Institute on Alcohol Abuse and Alcoholism Grant(AA-012821)~~
文摘Objective:The present study examines whether a long-term high salt diet causes hypertension and renal injury in normal subjects [Sprague-Dawley(SD) rats] and alters renal cytokine-related gene expression profiles.Methods: Four 10 week old male SD rats received a high salt diet(HS,8%) and the other 4 SD rats received a normal salt diet(NS,0.5 %) for 8 weeks.Mean arterial pressure(MAP) and renal damages such as albuminuria and histological renal injury were determined.The relative mRNA levels of 514 cytokine-related genes(normalized by β-actin) in rat kidneys following NS or HS were determined quantitatively through analysis of 4 sets of gene expression profiles using the mouse cDNA membrane microarrays.Results: We demonstrated that 8 weeks of HS diet increased MAP [(140.0±5.3) vs(112.0±2.2) mmHg;1 mmHg=0.133 kPa,P<0.01],albuminuria [(41.4±3.2) vs(20.1±4.5) mg/d;P<0.01],and caused histological renal injury in SD rats,compared to NS group.Of the 514 genes in the array,there were 27(5.25%) genes with significantly different expression in the kidney of SD rats with HS compared to those of SD rats with NS.Functional clustering analysis indicated the following functional pathways related to high salt diet-induced hypertension:(1) pro-inflammatory response(↑IL-17,CCL28;↓NFκbib);(2) endothelial dysfunction(↓VEGF-A,VEGF-B,endoglin);(3) pro-matrix formation(↑osteopontin,IGFBP-5;↓IFN-γ);and(4) attenuated cell survival and differentiation(↓CNTF,IGF-Ⅱ R,ephrin-B1).Northern blot confirmed that 8 weeks of HS diet significantly decreased renal expression of VEGF mRNA,compared to NS group(P<0.01).ELISA showed that HS diet significantly decreased renal protein levels of VEGF and CCL28.Conclusion: These findings support the hypothesis that hypertension can be induced in normal rats by a long-term high salt diet,which is associated with increased renal injury and marked changes in renal cytokine gene expression profiles that are closely related to the pro-inflammatory response,pro-matrix formation,endothelial dysfunction,and attenuated cell survival and differentiation.
