Caloric restriction inhibits renal artery ageing by reducing endothelin-1 expression.

BACKGROUND: The renal artery plays a central role in renal perfusion and is critical for proper renal function. Ageing is an independent risk factor for both impaired renal function and vascular disorders, and associated with an increase in the expression of the vasoconstrictor endothelin-1 (ET-1), and caloric restriction (CR) without malnutrition has been shown to be an effective inhibitor of renal dysfunction induced by ageing. The objective of this study was to determine whether CR-mediated alleviation of renal dysfunction is mediated by ET-1 expression. METHODS: The young (2 months, 2 M) and old (12 months, 12 M) Sprague-Dawley male rats were used and fed ad libitum. The 12-month-old rats were further divided into 12 M and 12 M-caloric restriction (CR) (30% calorie restriction). After 8 weeks, the renal tissues were showed by PAS staining, and age-related metabolic parameters and renal functions were detected in each group of rats. The inflammatory cytokines of interleukin (IL)-6, IL-1ß, tumor necrosis factor alpha (TNF-α), and transforming growth factor beta 1 (TGF-ß1) were analyzed using ELISA. The mRNA and protein expression in the renal artery were analysis by qRT-PCR and Immunoblot analysis. RESULTS: Ageing was associated with significant increases in 24 h urine protein content and serum triglyceride and cholesterol in 12 M rats, both of which were significantly inhibited in 12 M-CR. The mRNA expression and the secretion of IL-6, IL-1ß, TNF-α, and TGF-ß1 in the renal artery was significantly increased with ageing and inhibited by CR. CR also inhibited ageing-induced Edn1 (encoding ET-1) mRNA and protein expression in the renal artery. In addition, CR could regulate ET-1 expression by inhibiting the activation of NF-κB signaling and activation and induction in the expression of NF-E2-related factor 2 (Nrf2) and histone deacetylase and gene repressor sirtuin 1 (SIRT1), both of which play a central role in mitigating oxidative stress in young rats. CONCLUSIONS: Moderate CR can reverse the ageing related kidney dysfunction by reducing the ET-1 expression. CR might be used as an alternative to prevent the ageing induced renal artery dysfunction.

[Risk factors and short-term prognosis of acute kidney injury in elderly patients].

OBJECTIVE: To explore the risk factors and short-term outcomes of acute kidney injury (AKI) in elderly patients. METHODS: A total of 232 elderly AKI patients at Chinese PLA General Hospital from June 2008 to December 2009 were enrolled. They were divided into two groups according to their outcomes at 28 days and at 29 days to 3 months after AKI respectively. Their clinical data were analyzed to explore the risk factors and their effects on the outcomes of AKI. RESULTS: There were 215 males and 17 females with an average age of (86.7 ± 5.3) years. Thirty-eight cases (16.4%) died within 28 days after AKI and 57 (24.6%) died within 3 months. Infection (43.1%) was the major cause of AKI. The other causes included hypovolemia (19.0%), use of nephrotoxic drugs (16.8%) and cardiovascular events (15.1%) respectively. Logistic regression analysis revealed that low body mass index (BMI), oliguria, mechanical ventilation, hypoalbuminemia and peak serum level of creatinine (Scr >246.5 µmol/L) were the prognostic factors of AKI in those patients dying within 28 days after AKI (P < 0.05). Low BMI, hypoalbuminemia and high blood level of urea nitrogen (BUN) were the prognostic factors of AKI in those patients dying within 29 days to 3 months after AKI (P < 0.05). CONCLUSION: Infection, hypovolemia, use of nephrotoxic drugs and cardiovascular events are common causes of AKI in elderly patients.Low BMI, oliguria, mechanical ventilation, hypoalbuminemia, high level of BUN and peak level of Scr ( > 246.5 µmol/L) are the prognostic factors of AKI in elderly patients.

[Low testosterone levels are inversely correlated with carotid artery plaque formation in elderly women].

OBJECTIVE: To study the relationship between serum testosterone levels and the plaque formation of the carotid artery in a population-based cohort of independently living healthy women above 60 years of age. METHODS: Analysis of the healthy elders from a population-based cohort study in 9 communities of Beijing. Carotid intima-media thickness and atherosclerotic plaques were determined ultrasonographically. Serum testosterone levels were measured by immunoassay. The data were analyzed with ANOVA and logistic regression analysis. RESULTS: There was an inverse correlation between testosterone and plaque formation in old females (P < 0.01), while no association was found in males. Female with testosterone levels in the lowest quartile (< 0.49 nmol/L) had more risk of plaque formation (OR = 3.805, P < 0.01) after adjusted with age and other traditional factors of atherosclerosis. CONCLUSION: Testosterone concentrations are negatively associated with carotid artery atherosclerosis in old women in Beijing, experimental and prospective studies are needed to determine the possible therapeutic role of testosterone in atherosclerosis.

[Protective effect of sodium ferulate magnetic nanoparticle in septic kidney injury rats].

OBJECTIVE: To investigate the renal protective effect of sodium ferulate magnetic nanoparticle targeting therapy in septic rats receives norepinephrine treatment. METHODS: First we constructed sodium ferulate magnetic nanoparticle, Wistar male rats were randomly divided into 4 groups (n = 6): control group, septic group, norepinephrine treatment group (NE treatment group) and NE plus sodium ferulate magnetic nanoparticle treatment group (NE + SF group), septic rat model was reproduced by intravenous injection of lipolysaccharide (IPS) in rats in NE treatment group norepinephrine were used to elevate the blood pressure of septic rats, in NE + SF group sodium ferulate magnetic nanoparticle was injected via tail vein, magnetic field was placed near renal region. Urinary concentration of N-acetyl-beta-D-glucosaminidase (NAG), kidney injury molecule (KIM-1) and neutrophil gelatinase-associated lipocalin (NGAL), renal tissue concentration of malonaldehyde (MDA), superoxide dismutase (SOD), and serum concentration of blood urea nitrogen (BUN), creatinine (Cr), alanine aminotransferase (ALT), aspartate aminotransferase (AST) were measured 3 hours after treatment. RESULTS: After injected LPS via tail vein, systolic blood pressure, pH value, PaO2 and PaCO2 of arterial blood of septic rats decreased significantly. Systolic blood pressure, pH value, PaO2 and PaCO2 of arterial blood returned to baseline approximately after norepinephrine treatment, sodium ferulate magnetic nanoparticle targeting therapy did not change hemodynamic effects of norepinephrine. Compared with control group, urine NAG, KIM-1 and NGAL of sepsis group were increased significantly (P < 0.01), after treatment with norepinephrine, urine NAG, KIM-1 and NGAL of NE treatment group were elevated rapidly compared with those of sepsis group (P < 0.01), combined with sodium ferulate magnetic nanoparticles targeting treatment, urine NAG, KIM-1 and NGAL of NE + SF group were decreased significantly compared with those of sepsis group and NE treatment group (P < 0.01). Compared with control group, renal tissue MDA levels of septic rats increased significantly (P < 0.01), NE treatment could notably raise MDA levels compared with those of sepsis group (P < 0.01), renal tissue MDA levels of NE + SF group were decreased significantly compared with those of sepsis group and NE treatment group (P < 0.01). Compared with control group, renal tissue activities of SOD of sepsis group and NE treatment group were decreased significantly (P < 0.01), after targeted treatment with sodium ferulate magnetic nanoparticle, renal tissue SOD activities of NE + SF group increased significantly compared with those of sepsis group and NE treatment group (P < 0.01 vs sepsis group and NE treatment group). Serum BUN, Cr, ALT, AST levels did not significantly change in each groups. CONCLUSION: Sodium ferulate magnetic nanoparticle targeting therapy can effectively decrease urine NAG, KIM-1, NGAL and renal tissue MDA level, increase tissue SOD activity of sepsis group and NE treatment group rats, thus protect renal function of septic rats.