Clinical and pathological features of primary IgA nephropathy in patients of different gender / 西安交通大学学报(医学版)

Objective To explore the clinical and pathological features of primary IgA nephrology in patients of different gender.Methods The clinical manifestations,laboratory examination and renal pathology results were compared in 192 IgA nephrology patients.Results Not only the onset age of the male patients was older than that of the female ones (P0.05 ).Patients of different gender significantly differed in the renal-interstitial lesions grading (Z=-3.0432,P<0.05);to be more specific,the scores of glomerulosclerosis and renal tubule interstitia were higher in the male patients (P<0.05).Conclusion Patients of different gender differ in the clinical and pathological features of primary IgA nephrology.And clinical pathology of male patients is worse than that of female ones.

Effect of serum from patients with chronic renal insufficiency and indoxyl sulfate on lipid accumulation in macrophages in vitro / 南方医科大学学报

<p><b>OBJECTIVE</b>To investigate the pathologies of aortic root atherosclerotic lesion in uremic apoE-/- mice and explore the effect of serum from patients with chronic renal insufficiency (CRI) and the uremic toxin, indoxyl sulfate (IS), on the expression of cholesterol transporting receptors and lipid accumulation in macrophages in vitro.</p><p><b>METHODS</b>The uremic apoE-/- mouse model was established by surgical operation. Frozen sections of the aortic root were collected from uremic apoE-/- mice, sham-operated apoE-/- mice and C57BL/6J mice and stained with oil red O to calculate the relative area of atherosclerotic plaque. Murine macrophage RAW264.7 cell line was treated for 12 h with different concentrations of IS or serum samples from CRI patients and healthy individuals, and the mRNA expressions of cholesterol transporting receptors (SR-A1, CD36, ABCA1, ABCG1 and SR-B1) were detected. After treatment for 24 h, the cells were induced into foam cells to determine lipid contents using oil red O staining.</p><p><b>RESULTS</b>The relative area of the atherosclerotic plaques in the aortic root increased significantly in uremic apoE-/- mice compared with that in sham-operated apoE-/- mice. CRI serum (5%) and IS (250 µmol/L) obviously increased the mRNA expression of CD36 and lipid accumulation in the macrophages, but did not affect the mRNA expression of other cholesterol transporting receptors.</p><p><b>CONCLUSION</b>CRI can accelerate the progression of atherosclerosis through the mechanism that IS in CRI serum promotes lipid accumulation in macrophages by enhancing the mRNA expression of CD36, which contributes to the formation of foam cells.</p>

Effect of pioglitazone on balance of regulatory and effector T cells of ure-mic apolipoprotein E knockout mice in vitro / 中国病理生理杂志

AIM:To investigate the effects of pioglitazone on the quantity and function-related factors of regu-latory and effector T cells ( Treg and Teff ) of uremic apolipoprotein E knockout mice in vitro with or without the stimulation of atherosclerotic plaque-specific antigen oxidized low-density lipoprotein ( oxLDL) .METHODS:Uremic apolipoprotein E knockout mouse model was established by 2-step surgical procedure.After intervention with different concentrations ( 2μmol/L and 20μmol/L) of pioglitazone and PPARγantagonist GW9662 (5μmol/L) on splenocytes of uremic mice for 12 h in the presence or absence of oxLDL (2 mg/L), the levels of CD4 +CD25 +Foxp3 +Treg and IFNγ+CD4 +Teff were de-termined by flow cytometry.The mRNA expressions of Foxp3 and IFNγwas detected by real-time fluorescent quantitative PCR.RESULTS:In vitro, oxLDL induced a Treg/Teff imbalance in splenocytes from the uremic mice.Pioglitazone up-regulated the level of Treg and mRNA expression of Foxp3 in the presence of oxLDL, which was not antagonized by GW9662.Meanwhile, pioglitazone downregulated the level of Teff and mRNA expression of IFNγin the presence or ab-sence of oxLDL, which was reversed by GW9662.CONCLUSION:oxLDL induces a Treg/Teff imbalance in uremic apo-lipoprotein E knockout mice.Pioglitazone modulates the Treg/Teff imbalance probably through PPARγ-independent and-dependent mechanisms.

Inhibition of Notch signaling pathway promotes the differentiation of bone marrow mesenchymal stem cells into islet / 中华肾脏病杂志

Objective To investigate the effect of Notch signaling during bone marrow mesenchymal stem cells (BMSC) differentiating into islet in vitro.Methods The specific inhibitor of γ-secretase DAPT was used to inhibit the Notch signaling pathway.Mter induction,DTZ staining,indirect immunofluorescence staining,RT-PCR and Westenn blotting were used to detect the expression of insulin,glucagon,Pdx-1 and Ngn3.Results (1) Identification of BMSCs:Indirect immunofluorescence staining showed that BMSCs could express CD59 and CD90,which both were makrers of mesenchymal stem cells.Besides,BMSCs could express nerve culluar markers such as NSE,GFAP,suggesting multi-directional differentiation.(2) The result of MTT showed DAPT could inhibit the cell proliferation in a time-dependent manner and a dose-dependent mannar.Besides,DAPT could inhibit the expression of target gene of Notch signal pathway in a time-dependent manner and a dosedependent mannar.After treated by 1,5,20 μmol DAPT,the expression of Hes1 had reached to 92.06％,71.40％ and 46.89％ of controls respectively,suggesting efficiency of inhibition on Notch reached 7.94％,28.6％ and 53.11％ respectively (all P＜ 0.05).(3) Indirect immunofluorescence staining showed the expression of pancreas-specific markers such as insulin and glucagon were much higher in DAPT treated BMSCs than that in controls,which was confirmed by RT-PCR and Western blotting analyses.The proportion of insulin-producing cells differentiated from DAPT treated BMSCs was (74.03 ± 3.96)％,which was higher than that from controls[(36.49 ± 3.24)％,P＜ 0.05].(4)Furthermore,RT-PCR and Western blotting analysis showed that the expressions of Pdx-1 and Ngn3 were earlier than that of insulin and glucagon,and the expressions of Pdx-1 and Ngn3 were higher in DAPT treated BMSCs than that in controls.Conclusions Notch signaling pathway plays a role in the differentiation of BMSCs into islet in vitro.Pharmacological interference with Notch signaling pathway may provide a novel method to obtain islet for therapeutic use.

Immunological mechanism of class IV lupus nephritis through lymphocyte subsets and cytokine profile / 中南大学学报(医学版)

OBJECTIVE@#To obtain a global view of lymphocyte subset changes in the peripheral blood and cytokine profile in patients with class IV lupus nephritis (LN).@*METHODS@#A total of 30 patients with biopsy proven active class IV LN, 30 patients with biopsy proven active class V LN, and 30 healthy controls were enrolled. Serum concentration of Th1 cytokines (IFN-γ, IL-1, IL-2, and TNF-α) and Th2 cytokines (IL-4, IL-5, IL-6, IL-10, IL-13) were simultaneously analyzed by Fast Quant Human Th1/Th2 protein array. The expression of lymphocyte subsets was measured by flow cytometer. Clinical parameters such as urine protein of 24 h, autoantibodies and complement were detected. Pearson analysis was used to examine the relation between lymphocyte subsets and clinical parameters, cytokine and clinical parameters.@*RESULTS@#The patients with class IV LN had evident anemia (P<0.001), hypocomplementemia, and hypoalbuminemia (P<0.05). There were no significant difference both in the ratio and number of CD4+ lymphocytes between the controls and the patients. In the patients with class IV LN, the ratio and number of CD4+ lymphocytes were both lower than those of the controls (P<0.01). The ratio and number of CD20+ lymphocytes were both higher than those of the controls (P<0.05), and a significant decrease in CD4+CD25+Foxp3+ regulatory T cells (Tregs) was observed in the patients compared with healthy age-matched controls (P<0.001). The abnormality of lymphocytes in class IV patients was obviously notable, especially in CD4+CD25+Foxp3+ regulatory T cells. In class IV patients, most of the detected cytokines levels were markedly elevated as compared with the controls, including Th2 cytokines INF-γ (P<0.05), IL-2 (P<0.05) and TNF-α (P<0.01), and Th2 cytokines IL-4 (P<0.05), IL-6 (P<0.05), IL-10 (P<0.01) and IL-13 (P<0.01). Only 4 out of 9 cytokines significantly increased in class V patients. In addition to IL-2, all of them belonged to Th2 (IL-4, IL-10 and IL-13) cytokines. There was negative correlation between CD4+CD25+Foxp3+ regulatory cells and urine protein, anti-dsDNA titer or SLEDAI (r=-0.781, -0.746 and -0.646, respectively; P<0.05). There was positive correlation between IL-5 and anti-dsDNA titer (r=0.708, P<0.05), between IL-5 and creatinine (r=0.681, P<0.05), and between IL-10 and SLEDAI (r=0.877, P<0.01). There was also negative correlation between IL-10 and urine protein of 24 h (r=-0.659, P<0.05), between IL-10 and hemoglobin concentration (r=-0.856, P<0.01), and between IL-13 and urine protein of 24 h (r=-0.769, P<0.05). There was little correlation between cytokines and clinical parameters in patients with class V LN.@*CONCLUSION@#There is extensive abnormality in lymphocyte subsets and cytokine profile in patients with class IV LN, which may be the mechanism of immunosuppressive agents to treat patients with class IV LN.

Expression of urea transporters in sweat gland tissue of normal subjects and uremic patients / 南方医科大学学报

<p><b>OBJECTIVE</b>To explore the expression of urea transporters (UTs) in the skin and sweat glands of normal subjects and patients with uremia.</p><p><b>METHODS</b>Abdominal skin biopsy samples of patients with uremia and normal patients and apocrine sweat gland tissue from patients with bromidrosis were examined for the expression of UTs using immunohistochemistry and fluorescence immunoassay for quantitative analysis.</p><p><b>RESULTS</b>Both UT-A1 and UT-B1 proteins were expressed in the skin basal cell layer, eccrine sweat gland and apocrine sweat gland tissues. In uremic patients, N-UT-A1 and UT-B1 expressions were significantly higher than those in the control (P<0.05) but C-UT-A1 expression was similar (P>0.05).</p><p><b>CONCLUSION</b>UTs are expressed in human skin basal cell layer, eccrine sweat gland and apocrine sweat gland tissues, and their expressions are upregulated in uremic patients.</p>

Role of study on cytokine profiling in class V lupus nephritis from the perspective of systemic biology / 西安交通大学学报(医学版)

Objective To study the effects of cytokines Th1 and Th2 in Class V lupus nephritis (V-LN). Methods Serum concentration of Th1 cytokines (IFN-γ, IL-1, IL-2 and TNF-α) and Th2 cytokines (IL-4, IL-5, IL-6, IL-10 and IL-13) were simultaneously analyzed using fast quant human Th1/Th2 protein array, and Pearson analysis was used to evaluate the association between cytokines and clinical parameters. Results ① Cytokine profiling: Among the 9 cytokines detected simultaneously by fast quant human Th1/Th2 protein array, the expression of four cytokines was up-regulated obviously, namely, Th1 cytokines (IL-2) and Th2 cytokines (IL-4, IL-10 and IL-13); that of IL-10 was 10 times above the normal control. ② Pearson correlation analysis: There was a positive correlation between IL-10 and SLEDAI (r=0.877, P<0.01), but a negative correlation between IL-10 and hemoglobin concentration (r=-0.856, P<0.01). There was also a negative correlation between IL-4 and 24h urine protein (r=-0.754, P<0.05), between IL-13 and 24h urine protein (r=-0.769, P<0.05). Besides, IL-1 and creatinine were positively correlated (r=0.784, P<0.05). Conclusion There were extensively abnormal Th2 cytokines in V-LN patients, suggesting that anti-Th2 therapy may produce a marked effect on V-LN.

Protective effect of Shenqingyin Decoction on the kidney of experimental diabetic rats and its mechanism / 西安交通大学学报(医学版)

Objective To investigate the possible protective effect of Shenqingyin Decoction on the kidney of experimental diabetic rats and its possible mechanism. Methods Totally 40 rats with diabetes induced by streptozocin were divided into 4 groups: diabetes model group, Shenqingyin group, Benopril group and Shenqingyin-Benopril combination group. After 8 weeks' treatment, blood glucose, renal function and 24h urine protein were measured, and malondialdehyde (MDA) in renal tissues and urine, superoxide diamutase (SOD) activity and serum transformed growth factor-β_1(TGF-β_1) were tested; renal pathological changes were observed with light microscope as well. Results The serum BUN, Scre of all medicine groups were significantly improved, which did not significantly differ from that in control group (P>0.05). However, it had no obvious improving effect on blood sugar. The content of 24h urine protein in all medicine groups was significantly lower than that in model group (P<0.05 or P<0.01), and Shenqingyin-Benopril combination group had the significantly lower level than the other two medicine groups (P<0.01). MDA in renal tissues and urine, SOD activity and serum TGF-β1 in all medicine groups significantly differed from those in the model group (P<0.05 or P<0.01), and Shenqingyin-Benopril combination group had obvious difference with the other two medicine groups (P<0.01). Light microscopy showed amelioration of different degree in renal pathological changes, but with no significant differences in all medicine groups. Conclusion Shenqingyin Decoction has a protective effect on the kidney of experimental diabetic rats, and it has some synergetic effect when combined with Benopril. The mechanism may be related to inhibiting oxidative stress, improving the body's antioxidant ability and decreasing the expression of inflammatory factor TGF-β_1.

Diffuse proliferative lupus nephritis and membranous lupus nephritis: does different serum cytokine profiling suggest different immunological pathogenesis? / 中华风湿病学杂志

Objective To obtain a global view of cytokine profile in lupus nephritis (LN), and to co-mpare the pattern of cytokine profile in patients with different renal lesions, primarily diffuse proliferative lupus nephritis (Ⅳ-LN) and membranous lupus nephritis (Ⅴ-LN). Methods Thirtypatients with biopsy proven active LN (class Ⅳ, n=15; class Ⅴ, n=15) and 15 healthy controls were enrolled in this study. Serum conc-entration of Th1 cytokines (IFN-γ, IL-1, IL-2, and TNF-α) and Th2 cytokines (IL-4, IL-5, IL-6, IL-10, IL-13) were simultaneously analyzed using Fast Quant Human Th1/Th2 protein array. Results ① Cytokine profiling: in patients with class Ⅳ-LN, the levels of most of the detected cytokines elevated marked compared to normal controls, including both Th1 (IL-2, INF-γ and TNF-α) and Th2 (IL-4, IL-6, IL-10 and IL-13) cytokines. Among them, both Th1 (INF-γ and TNF-α) and Th2 (IL-6, IL-10 and IL-13) cytokines were 10 times higher than normal controls. However, patients with class Ⅴ LN demonstrated a different cytokine pro-filing compared to class Ⅳ LN. Only 4 out of 9 cytokines were significantly increased. In addition to IL-2, all of those cytokines produced by Th2 (IL-4, IL-10 and IL-13) as well as IL-10 was 10 times higher than normal controls. The main difference of cytokines between patients with class Ⅳ LN and patients with class Ⅴ LN was among Th1 cytokines (IFN-γ, IL-2 and TNF-α). There was a significant correlation between clinical manifestations and cytokines in class Ⅳ LN, especially among Th2 cytokine. There was positive correlation between IL-5 and anti-dsDNA titer(r=0.708, P<0.05), IL-5 and creatinin(r=0.681, P<0.05) and IL-10 and SLEDAI scores (r=0.877, P<0.0 ). On the other hand, there was also negative correlation between some Th2 cytokines and clinical manifestations. There was negative correlation between IL-5 and complement C3 level (r=-0.643, P<0.05), IL-10 and proteinuria(r=-0.659, P<0.O5), IL-10 and hemoglobin level (r=-0.856, P<0.001), as well as IL-13 and proteinuria (r=-0.769, P<0.05). In addition, IL-1 was positive correlated with SLEDAI, while it was negatively correlated with bemoglobulin level. As for class Ⅴ LN, there was positive correlation between IL-1 and creatinin level (r=0.784, P<0.05), but negative correlation between IL-4 and proteinuria (r=-0.754, P<0.05). Conclusion Patients with class Ⅳ renal lesion have shown a broad changes of cytokine activity, while up-regulation of Th2 cytokines is more predominant in patients with class Ⅴ LN. These suggest that the expression of different cytokines may be associated with different patterns of lupus renal lesions. These findings may shed light on the further exploring of the underlying mechanisms that mediate different patterns of renal lesions, as well as designing a rational therapeutic strategy for the treatment of LN.

The Clinical significance of urine transferrin in the type 2 diabetic nephropathy and primary chronic glomerular disease / 西安交通大学学报(医学版)

Objective To investigate the clinical significance of urine transferrin in the type 2 diabetic nephropathy and primary chronic glomerular disease. Methods The level of TRF and UAER in the urine of 114 patients with type 2 diabetes mellitus (T2DM), 108 patients with CGD and 30 healthy patients was measured by rate nephelometry and analyzed. Results Urine TRF significantly increased earlier than ALB at the early stage of DN; Linear correlation was found by correlation analysis between the level of TRF in urine level and the quantity of protein in urine. Conclusion TRF in urine obviously increased at the early stage of DN. It was more sensitive than UAER to reflect the early renal injury of DM. A statistically significant correlation was found between the TRF level and the quantity of protein in the urine.

The effect of blood purification on removing plasma inflammatory mediators in HFRS patients / 西安交通大学学报(医学版)

Objective To observe the removal of tumor necrosis factor-? (TNF-? ), interleukin-6 (IL-6) and endothelin-1 (ET-1) in continuous renal replacement therapy (CRRT) on hemorrhagic fever with renal syndrome (HFRS) patients, and investigate the effect of inflammatory mediators on HFRS. Methods A total of 40 patients with moderate or more severe HFRS were divided into two groups randomly. Continuous venous-venous hemofiltration (CVVH) was applied to the 20 cases in CVVH group, and hemodialysis (HD) was applied to the 20 cases in HD group. The levels of TNF-? and IL-6 were measured by enzyme-linked immunosorbent assay (ELISA), and ET-1 level was measured by radioimmunoassays (RIA). Results ① In comparing CVVH and HD groups, the days of oliguria (3.0?2.1, 6.0?3.4), incidence of complications (25%, 40%), and mortality (15%, 25%) had significant differences (P0.05). ④ In CVVH group, IL-6 and ET-1 could be detected constantly in filtrate, but TNF-? was not detectable. TNF-?, IL-6 and ET-1 were not detectable in dialysate. Conclusion Continuous blood purification can remove plasma inflammatory mediators. Therefore, it is helpful in recovering renal function, improving the prognosis of HFRS, and decreasing complications and mortality. CVVH is one of the best methods to treat HFRS.

The expression and effect of interleukin-13 in renal tissues in patients with primary glomerulonephritis / 西安交通大学学报(医学版)

Objective To study the expression of interleukin-13(IL-13) in renal tissues of several common pathologic types of primary glomerulonephritis(PGN).Methods Immunohistochemistry was used to examine the expression of IL-13 in renal tissues of 81 patients with PGN and 10 normal control cases.The correlation analysis was performed with biochemical and pathological indicators.Results Extensive expression of IL-13 was found in renal tissues of patients with PGN.The expression of IL-13 in renal tissues was positively correlated with the concentration of blood urea nitrogen,serum creatinine,the quantitation of urine protein and the crescent formation in glomerular(r=0.325,0.275,0.291,0.231,respectively).It was negatively correlated with glomerular filtration rate and serum albumin(r=-0.448,-0.296,respectively).Conclusion IL-13 participates in the process of inflammation reaction and crescent formation in the renal tissues in patients with PGN,and is correlated with the progression of renal function and the level of urea protein.

Alteration and significance of vascular endothelial growth factor in the serum of patients with glomerular diseases / 西安交通大学学报(医学版)

Objective To study the concentration alteration of serum vascular endothelial growth factor (VEGF) in patients with primary and secondary glomerular diseases (GD), the effect of immune inhibitors on the concentration, and analyze the relationship between VEGF concentration and some clinical indexes. Methods Serum VEGF concentration of GD patients was determined by sandwich ABC-ELISA. Results All of the GD patients had higher level of serum VEGF than the control group. Of the 5 groups divided according to the clinical classification, patients of chronic glomerulonephritis(CGN) group, latent glomerulonephritis(LGN) group, Henoch-Schonlein purpura nephritis(HSPN) group and lupus nephritis(LN) group had higher serum VEGF level than the control group, respectively, with no difference among the above groups. The patients without taking immune inhibitors had higher serum VEGF level than the control group,while no difference was observed between the patients taking immune inhibitors and the control group.Patients with glomerulonephritis had a significantly lower serum VEGF level after receiving immunosuppression aggressive therapy than before. The serum VEGF level of nephrotic syndrome in nephrotic phase was higher than in remission stage. In membranous glomerulonephritis serum VEGF correlated positively with 24-hour proteinuria excretion. The serum VEGF level correlated positively with anti-dsDNA Ab titer and the concentration of ? globulins in LN. Conclusion Cytokine VEGF is involved in the pathogenesis of glomerulonephritis, and in the occurrence and progression of proteinuria. Immunosuppression therapy can inhibit the expression of VEGF. In LN patients, the serum VEGF level is related to LN activity.