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Objective:To determine the plasma level of apelin in patients of maintenance hemodialysis (MHD) and to explore the relationship between apelin level and carotid atherosclerosis (AS) in MHD patients.Methods:A total of 92 MHD patients and 36 sex-and age-matched healthy subjects were enrolled in this study.The plasma level of apelin was evaluated by radiation immunoassay;serum endothelial injury markers including thrombomodulin,von Willebrand factor (vWF),and CD 146,and inflammatory factors including high sensitive C-reactive protein (hsCRP),IL-6 and TNF-α were determined by ELISA.Common Carotid arteries intima media thickness (CCA-IMT),cross-sectional calculated intima-media area (cIM area) area and atherosclerotic plaque were measured by non-invasive high-resolution B-mode ultrasonography.Results:The plasma levels of apelin was significantly decreased in MHD patients compared with healthy subjects (P＜0.01),accompanied with elevated plasma levels of thrombomodulin,vWF,CD 146,hsCRP,IL-6 and TNF-α (all P＜0.01).The plasma levels of apelinin in MHD patients with carotid artery plaques were obviously lower than those without plaques [(43.16± 10.12) pg/mL vs (61.43±16.25) pg/mL,P＜0.01].Plasma level of apelin was inversely related with CCA-IMT and cIM area (r=-0.355 and r=-0.297 respectively,all P＜0.01).Multiple stepwise regression analysis showed that plasma level of apelin was an independent risk factor for CCA-IMT and cIM area.Conclusion:The plasma apelin in MHD patients might take part in vascular endothelial injury and the progress of atherosclerosis.It plays an important role in the initiation and development of uremia associated atherosclerosis through elevating inflammatory factors including hsCRP,IL-6 and TNF-α levels.
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OBJECTIVE@#To examine the expression of notch3 in the kidneys of patients with primary hypertension and rats with spontaneous hypertension, and to explore the relationship of notch3 and hypertension renal fibrosis.@*METHODS@#Thirteen patients with primary hypertension served as a primary hypertension group (HP group), and 15 patients with kidney tumor served as a control group (CP group). The spontaneous hypertensive rats served as a primary hypertension group (SHR group, n=6), and WKY rats served as a control group (WKY group, n=6). Masson stainning was used to examine the collagen in the kidneys in the SHR group and the WKY group. Immunohistochemical staining was used to detect the levels of Notch3 in kidneys of the patients and the rats. The expression of snail mRNA in the kidneys in the SHR group and the WKY group was examined by real-time PCR.@*RESULTS@#Masson staining showed much more collagen in the SHR group than that in the WKY group (P<0.05); the expression of Notch3 in the HP group was much higher than that in the CP group ( 6.741±0.231 vs 0.763±0.358, P<0.01). The expression of Notch3 in the SHR group was much higher than that in the WKY group (5.487±0.774 vs 0.421±0.163, P<0.01), and The expression of snail mRNA was much higher in the SHR group than that in the WKY group (0.996±0.120 vs 0.208±0.090, P<0.01 ).@*CONCLUSION@#Notch3 may be related to the occurrence of hypertension renal fibrosis.
Subject(s)
Animals , Humans , Rats , Arteriosclerosis , Essential Hypertension , Fibrosis , Hypertension , Metabolism , Pathology , Kidney , Pathology , Kidney Diseases , Metabolism , Pathology , Rats, Inbred SHR , Rats, Inbred WKY , Receptor, Notch3 , Receptors, Notch , MetabolismABSTRACT
Objective:To investigate the calcium-phosphate metabolic condition in maintenance hemodialysis patients with chronic kidney disease (CKD), and to observe the effect of large dose calcitriol on secondary hyperparathyroidism (SHPT). Methods:We tested and compared the serum levels of calcium, phosphate, intact parathyroid hormone (iPTH), and alkaline phosphatase (AKP) in hemodialysis patients at different hemodialysis time (Group A with hemodialysis period≤3 years and Group B with hemodialysis period>3 years). We also detected those indexes before and after treating SHPT with large dose calcitriol. Twenty SHPT patients were divided into Group I (enlargement of parathyroid gland or nodule detected by color Doppler ultrasound) and Group II (normal parathyroid gland detected by color Doppler ultrasound). Results:In the maintenance hemodialysis patients, the serum phosphate was (2.11±0.38) mmol/L and iPTH was (581.11±487.75) pg/mL. The serum level of iPTH in Group B was higher than that in Group A [(828.13±690.39) pg/mL vs (477.94±324.73) pg/mL, P0.05). In Group II, the serum level of iPTH [before vs after:(1358.5±302.8) pg/mL vs (369.3±43.4) pg/mL, P Conclusion:Patients with longer time of hemodialysis have a higher level of iPTH. Large dose calcitriol can improve the clinical syndrome of SHPT, and decrease the level of iPTH and AKP in SHPT patients with normal parathyroid gland.
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Objective To determine the role of fosinopril and valsartan intervention in Klotho, matrix metalloproteinase-9 (MMP-9), tissue inhibitor of metalloproteinase-1 (TIMP-1) and plasminogen activator inhibitor (PAI-1) gene expression in hypertensive renal interstitial fibrosis (RIF) in the kidney tissue of spontaneously hypertensive rats (SHR). MethodsWe randomly divided 20 male 22-week-old SHR into 4 groups (5 in each group):a hypertension group (SHR group), a fosinopril group ［Fos group, 10 mg/( kg·d) gavage］, a valsartan group ［Val group, 10 mg/( kg·d) gavage］， and a fosinopril plus valsartan group ［Fos + Val group, fosinopril 10 mg/( kg·d) + valsartan 50 mg/( kg·d) gavage］. Another five 22-week-old male Wistar Kyoto rats (WKY) were used as controls. Through monitoring the weight of the rats, tail artery pressure, 24-hour urine protein by fosinopril and/or valsartan intervention after the 8-week trial. RT-PCR and Western blot were used to detect the mRNA and protein expression of Klotho, MMP-9, TIMP-1, and PAI-1 in the kidneys.Results RT-PCR showed that in the SHR group, Klotho mRNA and protein expression were significantly decreased(P＜0.01), while mRNA and protein expression of MMP-9, TIMP-1, and PAI-1 were significantly higher compared with the WKY group(P＜0.01). With fosinopril and / or valsartan intervention, Klotho mRNA expression in the Fos group (P＜0.01), Fos + Val group (P＜0.01), Val group (P＜0.05), Klotho protein expression in the Fos group(P＜0.05), Fos + Val group (P＜0.05), Val group (P＜0.01), were significantly increased compared with those in the SHR group. The mRNA and protein expression of MMP-9, TIMP-1, and PAI-1 in the Fos group, Val group, and Fos + Val group were significantly lower than those in the SHR group (P＜0.01). The expression of Klotho mRNA had negative correlation with the expression of MMP-9 mRNA (r= -0.864, P<0.01), TIMP-1 mRNA (r=-0.725, P<0.01) and PAI-1 mRNA (r=-0.785, P<0.01). The Klotho protein expression had negative correlation with the expression of MMP-9 protein (r=-0.614, P<0.05), TIMP-1 protein (r=-0.579, P<0.05), and PAI-1 protein (r=-0.552, P<0.05). Conclusion Anti-aging gene Klotho and the genes related with extracellular matrix degradation gene MMP-9, TIMP-1, PAI-1 are involved in hypertensive renal injury. The expression of Klotho and MMP-9, TIMP-1, and PAI-1 is closely correlated. Fosinopril and valsartan which increase the Klotho mRNA and protein expression can alter the expression of Klotho-MMPs/TIMPs, which may be the main mechanism to prevent interstitial fibrosis.