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Objective To investigate the expression level and clinical significance of growth differentiation factor-15 (GDF-15) in type 2 diabetic nephropathy.Methods Sixty-eight patients (DN) of type 2 diabetic nephropathy treated in our hospital from January 2012 to 2013 January were chosen,in the same period,66 cases with type 2 diabetes mellitus (DM) and 30 cases normal volunteers without family history of diabetes in (NC) were studied as control in this study.Their blood routine and renal functions were detected.GDF-15 level was examined by enzyme linked immunosorbent assay (ELISA),receiver operating characteristic curve (ROC) curve was used to analyze the diagnostic significance of GDF-15 level.Results The level of GDF-15 in blood of patients with type 2 diabetic nephropathy was significantly higher than that in patients with type 2 diabetes and normal control group.GDF-15 levels was negatively correlated with low density lipoprotein (LDL),fasting insulin (INS) and glomerular filtration rate (eGFR) (P ＜ 0.05),and positively correlated with cholesterol (TC),triglyceride (TG),high density lipoprotein (HDL),fasting blood glucose (FBG),glycosylated hemoglobin (HbA1c),high-sensitivity C-reactive protein (hsCRP),creatinine (SCR),urea nitrogen (BUN),24 h urinary albumin (mAlb),and urinary albumin excretion rate (URER) (P ＜0.05).GDF-15 level had no correlation with body mass index (BMI),systolic blood pressure (SBP),and diastolic blood pressure (DBP) (P ＞ 0.05).GDF-15 levels could be used to diagnose type 2 diabetic nephropathy with 82.2％ sensitivity and 70.2％ specificity.Conclusions GDF-15 level has important significance in the diagnosis and pathogenesis of type 2 diabetic nephropathy.
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Objective To explore the role of transforming growth factor-β1/serum and glucocorticoid induced kinase 1 (TGF-β1/SGK1) signaling pathway in diabetic nephropathy (DN).Methods Totally 60 clean grade healthy male Sprague-Dawley (SD) rats were divided into normal control (Con group,n =20) and diabetic model group (diabetic group,n =40).Type 2 diabetic animal model was induced by intraperitoneal injection of streptozotocin (STZ,45 mg/kg) to SD rats.Half of rats in each group were sacrificed after implemented for 4 weeks and 8 weeks,respectively.Fasting glucose,serum urea and creatinine,as well as urine protein in 24 h were detected.Pathological changes of rats' kidney cortex tissue were examined by hematoxylin-eosin staining.The expression of SGK1 was detected by immunohistochemistry in renal tissue.The mRNA level of SGK1 was analyzed by real-time polymerase chain reaction (PCR).The protein expression of TGF-β1 and SGK1 were determined by Western blotting.Results Compared to the control group,the blood glucose of the diabetic group rats was significantly increased,kidney hypertrophy index,serum urea and creatinine,24 h urine volume and urinary microalbumin as well as kidney index were significantly higher (P ＜0.05).The mRNA expressed of SGK1,protein expression of TGF-β1 and SGK1 were also increased obviously in the renal cortex of diabetic rats (all P ＜ 0.05 vs Control).Conclusions TGF-β1/SGK1 signaling pathway is closely related to the TIF damage of kidney cortex in diabetic rats.
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Objective To explore the relationship of serum tumor necrosis factor receptor 1 (TNFR1),and TNFR2 with early diabetic nephropathy in type 2 diabetes patients.Methods A total of 70 patients with type 2 diabetes and 35 healthy person were selected from December 2013 to November 2014 in the Fifth Hospital of Datong,the urinary albumin excretion rate (UAER) was determined,and were divided into three groups:normal control group (n =35),simple diabetes group (n =35),and early diabetic nephropathy group (n =35).Enzyme-linked immuno sorbent assay (ELISA) method was used to determine TNFR1 and TNFR2.Results Compared to normal control group [TNFR1 (302.5 ± 60.0) pg/ml,TNFR2 (62.1 ±9.8)pg/ml],simple diabetes group [TNFR1 (515.1 ±78.1)pg/ml,TNFR2 (178.5 ±38.9)pg/ml],and early diabetic nephropathy group [TNFR1 (1 066.8 ± 205.6) pg/ml,TNFR2 (279.6 ± 37.1)pg/ml] were all increased;and early diabetic nephropathy group was higher than simple diabetes group (P＜ 0.05).The levels of TNFR1 and TNFR2 were positively correlated with age,course,glycated hemoglobin (HbA1c) levels(P ＜0.01),and were negatively correlated with high density lipoprotein cholesterol (HDL-C) and estimated glomerular filtration rate (eGFR) (P ＜0.01).The multiple stepwise regression analysis in eGFR had significant effects on TNFR 1 and TNFR 2 levels (P ＜ 0.01).Conclusions The levels of TNFR1,and TNFR2 in early diabetic nephropathy were increased.TNFR1 and TNFR2 may become new markers to evaluate early diabetic nephropathy.
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Objective Serum indicators of oxidative protein damage (OPD) were analyzed to explore the effect on renal MMP/TIMP system of OPD in diabetic nephropathy. Methods AOPP levels and PCO levels were measured by modified Witko-Sarsat's method and 2, 4-dinitrophenylhydrazine spectrophotometric method, expression of serum MMP-2 were determined by ELISA, and MMP-2 activity were detected by zymography . Results AOPP levels of group DN1, group DN2 were higher than those of group DM(78.23±19.30 vs 61.25±12.13,101.59±30.22 vs 61.25±12.13,F＝41.988,P＜0.01). PCO levels of group DN1 and group DN2 were higher than those of group DM (0.84±0.03 vs 0.66±0.02,1.05±0.05 vs 0.66±0.02,F＝205.763,P＜0.01). Pearson correlation analysis indicated AOPP and PCO were positively correlated with the expression (r＝0.460,0.480,P＜0.05) and activity (r＝0.385,0.560,P＜0.05) of serum MMP-2. Multiple stepwise regression analysis showed that AOPP and PCO were major influential factors of serum MMP-2 expression (P＜0.05,P＜0.01) and activity(P＜0.01,P＜0.05). Conclusions OPD might be involved in the imbalance of renal matrix metabolism, which was correlated with the development of diabetic nephropathy.
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Objective To investigate the relationship and mechanism of the heme oxygenase-1 expression in peripheral blood mononuclear cells (PBMC) and the oxidative stress in diabetic nephropathy. Methods Two groups of diabetic patients with or without diabetic nephropathy and a normal control group were enrolled in this study. Fasting blood glucose (FBG), HbA1c, serum MDA level, ROS level, HO-1 mRNA level and HO-1 protein expression in PBMC were determined. Results In control group, diabetic group and diabetic nephropathy group , the MDA levels significantly increased[(14.23±5.07)nmol/ml vs (24.90±7.12)nmol/ml vs (43.83±16.97)nmol/ml](F＝37.022,P＜0.01), the ROS levels significantly increased (113.18±58.59 vs 364.54±88.67 vs 524.35±162.51)(F＝68.369,P＜0.01) and the HO-1 protein expression also increased significantly (22.84±9.98 vs 36.72±15.85 vs 58.1±15.93)(F＝31.302,P＜0.01). There was a positive correlation among the HO-1 mRNA, protein expression and MDA level(r＝0.407,0.429,P＜0.05). Conclusions There existed a severer oxidative stress condition in patients with diabetic nephropathy compared with the patients without diabetic nephropathy. HO-1 could be a potential pathway to ameliorate oxidative stress in diabetic kidney disease patients.
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Objective To observe the expressions of c-Ski in renal tissue of diabetic nephropathy rats, and discuss its significance. Methods Wistar male rats were randomly assigned to 3 groups: Control group, diabetic group and treatment group. Rats were killed at the 16th week after experiment. Histopathologic changes,in renal tissue were observed and immunohistochemistry was performed to investigate the expression of TGF-β1, α-SMA and c-Ski. Results The expression of c-Ski had a negative correlation with TGF-β1 and α-SMA. Compared to diabetic group, the expression of c-Ski was significantly increased in treatment group. Conclusion c-Ski may be a protective factor of tu-bular epithelial-myofibroblast transformation.