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Objective To establish albumin-creatinine ratio (ACR) reference value of the rural population in Hebei province.Methods This study enrolled 5154 participants. By excluding subjects with hypertension, diabetes, dyslipidemia, cardiovascular and cerebrovascular diseases, kidney diseases, and overweight condition, as well as those with an estimated glomerular filtration rate (eGFR)<60 ml/(min·1.73 m), apparently healthy subjects (1168) were selected. Urine albumin was measured by using the immunoturbidimetic method, serum creatinine was measured by using Jaffe's kinetic method on a morning spot-urine sample, and ACR was calculated. The 95th percentile of ACR in the healthy subjects was used as the normal upper limit.Results The normal upper limit of ACR was 28.71 mg/g (3.25 mg/mmol) for males and 31.85 mg/g (3.60 mg/mmol) for females. Based on this ACR reference value, the age-gender standardized prevalence of albuminuria in the rural areas of Hebei province was 12.9%.Conclusion The ACR reference value in the rural of Hebei province is higher than that of the Western population.
ABSTRACT
<p><b>OBJECTIVE</b>To investigate the effects of rapamycin on cholesterol homeostasis and secretory function of 3T3-L1 cells.</p><p><b>METHODS</b>The in vitro cultured 3T3-L1 cells (preadipocytes) were divided into control group, rapamycin 50 nmol/L group, rapamycin 100 nmol/L group, and rapamycin 200 nmol/L group. Intracellular cholesterol level was measured by oil red O staining and high performance liquid chromatography. The secretion levels of leptin and adiponectin were assayed by enzyme-linked immunosorbent assay. The mRNA and protein expressions of peroxisome proliferator-activated receptor (PPARgamma) were assayed by quantitative real-time polymerase chain reaction and Western blot.</p><p><b>RESULTS</b>Oil red O staining showed rapamycin down-regulated 3T3-L1 cells differentiation and lipid accumulation. Quantitative measurement of cholesterol with high performance liquid chromatography showed that the concentrations of free cholesterol in rapamycin treatment groups had a significant reduction. The concentrations of free cholesterol in the control group, rapamycin 50 nmol/L group, rapamycin 100 nmol/L group, and rapamycin 200 nmol/L group were (12.89 +/- 0.16), (9.84 +/- 0.45), (9.39 +/- 0.46), and (8.61 +/- 0.34) mg/ml, respectively (P < 0.05), and the concentrations of total cholesterol were (12.91 +/- 0.50), (9.94 +/- 0.96), (10.45 +/- 2.51), and (9.53 +/- 0.63) mg/ml, respectively. The leptin concentrations in the control group, rapamycin 50 nmol/L group, rapamycin 100 nmol/L group, and rapamycin 200 nmol/L group were (19.02 +/- 0.52), (16.98 +/- 0.11), (15.62 +/- 0.01), and (13.84 +/- 0.66) ng/ml, respectively. The mRNA expressions of PPARgamma in the rapamycin 50 nmol/L group, rapamycin 100 nmol/L group, and rapamycin 200 nmol/L group were significantly lower than that in control group (P < 0.05). The protein expressions of PPARgamma in the rapamycin 50 nmol/L group, rapamycin 100 nmol/L group, and rapamycin 200 nmol/L group were 80%, 74%, and 61% of that in control group (P < 0.05). After the cells were treated with rapamycin 100 nmol/L, PPARgamma blocking agent GW9662 10 micromol/L, and PPARgamma agonist troglitazone 10 micromol/L, respectively, for 96 hours, the mRNA expression of PPARgamma was (0.60 +/- 0.14), (0.67 +/- 0.03), and (1.30 +/- 0.14) of that in control group (P < 0.05). The protein expression showed a similar trend with mRNA expression (P < 0.05). After the cells were treated with rapamycin 100 nmol/L, PPARgamma blocking agent GW9662 10 micromol/L, and PPARgamma agonist troglitazone 10 micromol/L, respectively, for 96 hours, the expression of leptin in the control group, rapamycin 50 nmol/L group, rapamycin 100 nmol/L group, and rapamycin 200 nmol/L group was (19.02 +/- 0.52), (15.62 +/- 0.10), and (14.45 +/- 1.01) and (18.07 +/- 0.66) ng/ml, respectively (P < 0.05 compared with the control group).</p><p><b>CONCLUSIONS</b>By downregulating the expression of PPARgamma, rapamycin can decrease cholesterol accumulation in 3T3-L1 cells and inhibit its leptin-secreting capability. This finding may provide a possible explanation for rapamycin-induced hyperlipidemia in clinical practice.</p>
Subject(s)
Animals , Mice , 3T3-L1 Cells , Adipocytes , Metabolism , Cholesterol , Metabolism , Leptin , Metabolism , PPAR gamma , Genetics , Metabolism , Sirolimus , PharmacologyABSTRACT
<p><b>OBJECTIVE</b>To investigate the effects of rapamycin on cholesterol homeostasis of glomerular mesangial cells and the underlying mechanisms.</p><p><b>METHODS</b>Intracellular cholesterol accumulation was measured by Oil Red O staining and high performance liquid chromatography. The effects of rapamycin on interleukin-1 beta (IL-1 beta)-induced mRNA and protein changes of low-density lipoprotein receptor (LDLR) and ATP-binding cassette transporter A1 (ABCA1) were assayed by quantitative real-time PCR and Western blot. Transient expressions of 3 types of mammalian target of rapamycin (mTOR), including mTOR-WT (wild type), mTOR-RR (rapamycin resistant, with kinase activity), and mTOR-RR-KD (rapamycin resistant, without kinase activity), were obtained by plasmid transfection.</p><p><b>RESULTS</b>Rapamycin had no significant influence on intracellular cholesterol concentration under normal condition, but it significantly decreased the intracellular cholesterol concentration in the presence of IL-1 beta. Rapamycin dose-dependently suppressed the increased expression of LDLR induced by IL-1 beta and up-regulated the suppressed expression of ABCA1 caused by IL-1 beta. Transient expression of 3 types of mTOR all reduced ABCA1 mRNA expression significantly, which all could be overroded by rapamycin.</p><p><b>CONCLUSIONS</b>Rapamycin may contribute to the maintaining of glomerular mesangial cell intracellular cholesterol homeostasis under inflammatory state by both reducing cholesterol uptake and increasing cholesterol efflux. And the effect may be not completely mediated by mTOR.</p>