The involvement of inflammatory processes has been recognized in development and/or progression of diabetic nephropathy. However, the mechanisms involved in the pathogenesis of renal inflammation have not been completely understood. In this study, we tested the hypothesis that accumulation of advanced oxidation protein products (AOPPs), which occurs in diabetes, may promote inflammatory responses in diabetic kidney. Streptozotocin-induced diabetic rats were randomized to iv injection of vehicle, native rat serum albumin (RSA), and AOPPs-modified RSA (AOPPs-RSA) in the presence or absence of oral administration of apocynin. A control group was followed concurrently. Compared with RSA- or vehicle-treated diabetic rats, AOPPs-RSA-treated animals displayed significant increase in renal macrophage infiltration and overexpression of monocyte chemoattractant protein-1 and TGF-β1. This was associated with deteriorated structural and functional abnormalities of diabetic kidney, such as glomerular hypertrophy, fibronectin accumulation, and albuminuria. AOPP challenge significantly increased nicotinamide adenine dinucleotide phosphate (NADPH) oxidase-dependent superoxide generation in renal homogenates and up-regulated membrane expression of renal NADPH oxidase subunits p47phox and gp91phox. All these AOPPs-induced perturbations in diabetic kidney could be prevented by the NADPH oxidase inhibitor apocynin. These data suggest that chronic accumulation of AOPPs may promote renal inflammation in diabetes probably through activation of renal NADPH oxidase.
Huang Qi (root of Astragalus membranaceus) and Dang Gui (Angelica sinensis), two of the most widely used herbs in traditional Chinese medicine, have been proven to be effective in the treatment of diabetes mellitus (DM) although the underlying molecular mechanisms are not fully elucidated. This study was designed to investigate the protective effect of Dang Gui and Huang Qi mixture (GQM) on the development of diabetic nephropathy in rats with streptozotocin (STZ)-induced DM and the possible underlying molecular mechanism. The diabetic animal model was made by a single intraperitoneal injection of STZ and then treated with GQM or benazepril. Blood glucose, triglyceride (TG), cholesterol (CHO), high density lipoprotein (HDL), serum creatinine (Scr), creatinine clearance rate (Ccr), blood urea nitrogen (BUN), urine β2-microglobin (β2-MG), kidney/body weight (K/B) ratio, glomerular area (GA), renal transforming growth factor-β1 (TGF-β1) mRNA expression and blood and renal angiotensin II (AngII) expression were determined 8 weeks after the treatment. The blood glucose, CHO and TG levels, BUN, SCr, Ccr. K/B ratio, GA, the excretion of β2-MG, renal TGF-β1 mRNA expression and blood and renal AngII expression were significantly increased while the HDL level was decreased 8 week after STZ injection. The changes in blood glucose, TG, CHO and HDL were reversed by GQM, not by benazepril, whereas the changes in other variables were reversed by both GQM and benazepril. Our results suggest that GQM alleviates the disorder in blood glucose and lipids, protects against the progression of renal nephropathy in diabetic rats, probably by inhibiting the expression of AngII and TGF-β1 mRNA.
Objective The efficacy of combined treatment consisting of enalapril and folic acid (FA) was compared to that of enalapril alone in reducing the serum uric acid (UA) levels in adult hypertensive patients in China. Methods Patients with mild to moderate hypertension (n=480) were randomly assigned to one of three treatment groups: (1) 10 mg enalapril (control group), (2) 10 mg enalapril plus 0.4 mg FA (low-FA group) or (3) 10 mg enalapril plus 0.8 mg FA (high-FA group) daily for eight weeks. The primary outcome was the UA ratio (week 8 UA: baseline UA). Results The final analysis included 450 patients (43.1% men, 27-75 years of age). An adjusted multivariable regression analysis revealed no significant differences in the UA ratio between the three groups after eight weeks of treatment. In the subgroup analysis stratified according to the baseline UA level, the high-FA group demonstrated a significantly greater UA-lowering response among the patients with an elevated baseline UA concentration (UA ≥310 μmol/L) [median UA ratio (25th percentile, 75th percentile): 0.94 (0.83, 1.01)], compared with that observed in the control group [0.97 (0.90, 1.00), p=0.025]. Similar results were found in the participants with baseline hyperuricemia (HUA; UA: men >420 μmol/L, women >350 μmol/L). Conclusion In this sample of adult hypertensive patients, the administration of a daily dose of 10 mg of enalapril combined with 0.8 mg of FA had a greater beneficial effect on the serum UA levels than did that of 10 mg of enalapril alone in patients with either an elevated UA concentration or HUA.
Background We aimed to examine the risk factors for renal function decline (RFD) in a community-based cohort of a rural Chinese population with normal kidney function (estimated glomerular filtration rate, eGFR ≥60 mL/min/1.73 m 2 ), both for the population as a whole and stratified by sex. Methods 2518 participants were included in the current analysis. RFD was defined as follows: a drop in the eGFR category accompanied by a 25% or greater drop in eGFR from baseline; or a sustained decline in eGFR of more than 5 mL/min/1.73 m 2 /year. Results The incidence rate of RFD was 8.7% (women 7.4% and men 9.8%). In the multivariable logistic regression model, the ORs (95% CI) of developing RFD was 1.60 (1.01 to 2.54) for men versus women, and 1.51 (1.09 to 2.08) for participants with obesity or abdominal obesity versus none (1.35 (0.85 to 2.14) for men, and 1.65 (1.04 to 2.64) for women). However, prehypertension (OR=1.64; 95% CI 1.02 to 2.63) or hypertension (2.05; 1.21 to 3.47), higher mean blood pressure (≥90 vs <80 mm Hg, 2.63; 1.11 to 6.20), higher pulse pressure (≥50 vs <40 mm Hg, 2.00; 1.26 to 3.18), lower high-density lipoprotein cholesterol (<0.9 vs ≥0.9 mmol/L, 2.65; 1.08 to 6.50) and low physical activity levels (vs high, 3.11; 1.59 to 6.10) were major risk factors for RFD in men. Current smoking (3.22; 1.22 to 2.64) and worse self-reported health (vs better, 2.57; 1.20 to 5.50) were major risk factors for RFD in women. Conclusions Our findings suggested that sex-specific risk factors should be considered in prevention of RFD in the Chinese rural population with normal kidney function.
To develop and evaluate the short version of patient reported outcomes (PROs) questionnaire for gastric stuffiness (Wei Pi) patients with modern test theory and technologies, hoping to provide testing tools for related clinical practice and scientific researches with higher quality and less administrative and response burdens.Using descriptive study design, clinical data were collected with sociological questionnaire and previous developed full items version of PROs instrument for gastric stuffiness (Wei Pi) patients via field and online surveys between Sep 2011 and Mar 2012. The statistical analysis group identified the termination parameters firstly, and then selected items with discrimination, fitting residual, item information curve (IIC) , item characteristic curve (ICC), and the rank of computerized adaptive testing (CAT) select proportion, etc. After assumption evaluation of item response theory (IRT), IIC, ICC, difficulty coefficient distribution, items-response relation and thresholds, etc. were used for psychometric evaluation of instrument.A total of 331 patients [Ages: 31.99 +/- 10.29 yrs; Male: 186 (56.3%)] were enrolled in statistical analysis. The test termination criterion was Max SE = 0.2 or Max items number =16. After items selection, a 15-item short version of instrument, which contains symptoms facet (8 items) and impact facet (7 items) was generated. With good unidimensionality, local independence, and monotonicity, the IC and ICC in IRT analysis showed good working capability of the questionnaire. The difficulty coefficient distribution and items-response relation were also rational, as well as response thresholds.The short version of PROs instrument for adult gastric stuffiness (Wei Pi) patients was successfully developed and assessed. The instrument with good methodological and reporting quality could be used in clinical and scientific evaluating their symptoms and impact.