Effect of high glucose on intracellular cholesterol content in rat glomerular mesangial cells / 中国医师杂志

Objective:To investigate the effect of high glucose on intracellular cholesterol content in rat glomerular mesangial cells and the underlying mechanism.Methods:Rat glomerular mesangial cells were cultured in vitro and divided into high glucose culture group (high glucose group, medium glucose concentration of 30 mmol/L) and normal glucose culture group (normal group, medium glucose concentration of 5.5 mmol/L). Lipid content was determined by oil red O staining and spectrophotometer colorimetry at 24, 36 and 48 h of culture. Intracellular protein imprinting was used to detect the expression of low density lipoprotein cholesterol receptor (LDLR) and adenosine triphosphate binding cassette A1 (ABCA1). Results:Oil red O staining showed that the intracellular lipid drops in the high glucose group were less than those in the normal group at 36 h, and there was no significant difference between the two groups at 24 h and 48 h of culture. The total cholesterol (TC) and cholesterol ester (CE) in glomerular mesangial cells of rats in the high glucose group were significantly lower than those in the normal group ( P=0.028, 0.029), while there was no significant difference in the free cholesterol (FC) between the two groups ( P=0.306). There was no significant difference in TC, CE and FC between the two groups at 24 and 48 h of culture (all P>0.05). The expression of LDLR in mesangial cells of rats in high glucose group was significantly lower than that in normal group at 24, 36 and 48 h of culture ( P=0.043, 0.004, 0.028), and the expression of ABCA1 was significantly higher than that in normal group at 24, 36 and 48 h of culture, ( P=0.050, 0.009, 0.006). Conclusions:High glucose may reduce intracellular cholesterol content in rat glomerular mesangial cells by reducing LDLR protein expression and increasing ABCA1 protein expression.

Clinical value of neutrophil to lymphocyte ratio in maintenance hemodialysis patients / 中华全科医师杂志

Objective To investigate the clinical value of neutrophil to lymphocyte ratio (NLR) in evaluation of inflammation and prediction of cardiovascular events in maintenance hemodialysis (MHD) patients.Methods One hundred and eight stable MHD patients were recruited from Dialysis Center of Beijing Tongren Hospital from October 2015 to December 2015.The general information,complete blood count,hsCRP,biochemical test,iron metabolic indicators,pre-dialytic systolic blood pressure (SBP) and diastolic blood pressure (DBP) were recorded.MHD patients were divided into the low NLR group and high NLR group according to the median of NLR (2.82).All patients were followed up for 18 months,cardiovascular events (CVE) were recorded during this period.Results In the high NLR group the dialysis vintage,white blood cell count,neutrophil count,NLR and hsCRP were significantly higher than those in the low NLR group [(88.0 ± 50.4) vs.(62.4 ± 40.6) months (t =2.48,P =0.02),(6.96 ± 1.82) × 109/L vs.(5.83 ± 1.33) × 109/L(t =3.14,P=0.00),(4.94 ± 1.38) × 109/L vs.(3.36 ±0.87) × 109/ L(t=6.08,P=0.00),(4.16±1.25) vs.(2.15 ±0.46) points(t=9.48,P=0.00),(7.85±4.92) vs.(3.13 ± 2.23) mg/L (t =4.97,P =0.00)].In the high NLR group lymphocyte count and transferrin saturation were significantly lower than those in the low NLR group[(1.25 ± 0.40) × 109/L vs.(1.58 ± 0.34) ×109/L,t=3.97,P=0.00;(25.7±10.2)％ vs.(32.6±17.2)％,t=2.17,P=0.03].There were no significant differences in age,sex,diabetes proportion,pre-dialytic SBP,pre-dialytic DBP,urea clearence index(Kt/V),hemoglobin,serum ferritin,serum calcium,serum phosphorus,intait parathyroid hormone,albumin,serum creatinine,carbon dioxide binding capacity and blood lipids between the two groups (P ＞ 0.05).Bivariate correlation analysis showed that NLR was positively correlated with dialysis vintage and hsCRP (r =0.311,P =0.01;r =0.574,P =0.00);white blood cell count and neutrophil count were positively correlated with hsCRP (r =0.327,P =0.00;r =0.488,P =0.00).During follow-up period 9 cases of CVE (16.7％) and 20 cases of CVE (37.0％) occurred in the low NLR group and high NLR group,respectively (x2 =5.70,P =0.03).Cox regression analysis showed that age,NLR and serum phosphorus level were risk factors of CVE in MHD patients (HR =1.075,P =0.00,HR =1.646,P =0.00;HR =1.912,P =0.02).Conclusion NLR can predict inflammation and is one of the risk factors for CVE in MHD patients.

Investigation on the Relationship of H2S and the Accumulation of Extracellular Matrix of the Diabetic Nephropathic Rats By BrdU labeling method / 医学研究杂志

Objective To explore the relationship of hydrogen sulfide (H2S) and the extracellular matrix of the diabetic nephropathic rats' glomerulars.Methods Twenty-one male rats(Sprague-Dawley) were randomly divided into Control group(n =7),DN group (n =7) and DN + H2 S group (n =7).Diabetes was induced in the rats except Control group rats by STZ (60mg/kg).The rats of the DN + H2S group were injected with NaHS every day,and rats of other groups were injected with NS.Eight weeks later,three groups were compared in proteinuria of 24 hours,KW/BW,the proportion of the BrdU positive cell and the distribution of α-SMA in glomerulars.Results Compared with Control group,DN group rats were significantly increased in proteinuria of 24 hours and KW/BW (P ＜ 0.01).Kidney biopsy in DN groups rats were typical DN pathological manifestation.In treatment with NaHS,the DN rats in the DN + H2S group were decreased in proteinuria of 24 hours,KW/BW,the proportion of the BrdU positive cell and the distribution of α-SMA in glomerulars (P ＜ 0.01),and was similar with the control group in the pathology of renal.Conclusion The H2 S control the multiplication of myofibroblast,and were decreased in the distribution of α-SMA in glomerulars.The H2S treatment may put off the progress of the extracellular matrix in the DN rats' glomerulars.

Troglitazone reduces the inhibitory effect of sirolimus on premature 3T3-L1 cell's function / 中华肾脏病杂志

Objective To investigate the effects of troglitazone on cholesterol homeostasis and secretion of 3T3-L1 cells by sirolimus and the underlying mechanisms. Methods In vitro cultured 3T3-L1 cells were divided into control group,sirolimus (100 nmol/L) group,sirolimus(100nmol/L)+ troglitazone (10 μmol/L) group and troglitazone (10 μmol/L) group.High performance liquid chromatography (HPLC) was used to measure intracellular cholesterol accumulation.ELISA was used to measure leptin excretion.Quantitative real-time PCR and Western blotting were used to examine mRNA and protein expression of PPARγ. Results Free cholesterol of sirolimus +troglitazone group was 1.19 times of sirolimus group (P＜0.05).The leptin secretion levels of control group,sirolimus group,sirolimus+troglitazone group and troglitazone group were (19.02±0.52) μg/L,(15.62±0.47) μg/L,(16.45±0.51) μg/L,(18.07±0.66) μg/L,respectively.And the leptin secretion level of sirolimus+ troglitazone group was 1.05 times of sirolimus group (P＜0.05).The PPARγmRNA expressions of sirolinus group,sirolimus + troglitazone group and troglitazone group were 0.60±0.14,1.12±0.27,1.30±:0.14 folds of control,and the PPARγ mRNA expression of sirolimus + troglitazone group was higher than that of sirolimus group (P＜0.05).PPARγ protein expression had the same tendency. Conclusion Troglitazone reduces the inhibitory effect of sirolimus on PPARγ transactivation and the inhibitory effect of sirolimus on 3T3-L1 cells differentiation and adipogenesis.

Enhanced uptake of human mesangial cell line to oxidized low density lipoprotein stimulated by interleukin-1β partly through the lectin-like oxidized low-density lipoprotein receptor pathway / 中华肾脏病杂志

Objective To analysis if intedeukin-1β (IL-1β) can regulate human mesangial cells (HMC) to uptake oxidized low density lipoprotein (Ox-LDL) and if the effect of IL-lβ be changed through the lectin-like oxidized low-density lipoprotein receptor 1 (LOX-l)pathway. Methods The uptake of HMC to Ox-LDL stimulated by IL-1β was observed using Oil Red "O" and flow cytometry. The level of LOX-1 in HMC induced by IL-1β and Ox-LDL was examined using real-time PCR and Western blotting. Results Uptake of Ox-LDL and Dil-Ox-LDL by HMC was up-regulated upon stimulation with IL-1β in a dose- and time-dependent manner. Intracellular mean fluorescence density of Dil-Ox-LDL with LOX-1 blocker in IL-1β stimulation group was decreased compared to that without blocker. The peak level of LOX-1 mRNA reached after 6 h of stimulation and was as high as 6.87-fold of control. IL-1β could induce LOX-1 mRNA expression in a dose-dependent manner. Treated with 10 μg/L IL-1β for 12 h, the upregulation effect on LOX-1 mRNA was as high as 6.57-fold of control. IL-1β could induce LOX-1 protein expression in a time- and dose-dependent manner. The peak level of LOX-1 protein reached after 24 h of stimulation of 5 μg/L IL-1β and was as high as 1.88-fold of control. Treated with 10 μg/L IL-1β for 24 h, the up-regulation effect on LOX-1 protein reached peak and was as high as 2.57-fold of control. IL-1β could induce LOX-1 mRNA and protein expression in a dosedependent manner. Conclusion The expression of LOX-1 can be up-regulated by IL-1β in a dose-dependent manner and the enhanced uptake of HMC to Ox-LDL stimulated by IL-1β partly through the LOX-1 pathway, which means the dyslipidemia of HMC can be enhanced by inflammatory cytokines.

Effects of sodium ferulute on experimental arrhythmias / 中国药理学通报

AIM To study effect of sodium ferulute on experimental arrhythmias. METHODS Arrhythmias were induces by drugs and myocardial ischemia. RESULTS Sodium ferulute 0 6 g?kg -1 iv antagonized arrhythmias induced by ouabain, adrenalin and myocardial ischemia( P