Effects of Tacrolimus Combined with Valsartan in Immunosupperessive regimen on Renal Function and Lipid Metabolism in Patients with Chronic Allograft Dysfunction and Its Mechanism Study / 中国药房

OBJECTIVE： To investigate the effects of tacrolimus combined with valsartan in immunosuppressive regimen on renal function， lipid metabolism and matrix metalloproteinase 2 （MMP-2）， MMP-9， tissue inhibitors of matrix metalloproteinases 2 （TIMP-2） and transforming growth factor-β （TGF-β） in patients with chronic allograft dysfunction （CAD）. METHODS： CAD patients admitted to nephrology department of our hospital from Mar. 2016 to Jun. 2018 were enrolled in group A， B， and C according to the random number table， 34 cases in each group. Group A was given cyclosporin A+Mycophenolate capsules+Prednisone acetate tablets； group B was treated with tacrolimus+Mycophenolate capsules+Prednisone acetate tablets； group C was treated with valsartan on the basis of group B； they were treated for continuous 3 months. Renal function indexes （24 h urinary protein， Scr）， lipid metabolism indicators （TC， TG， HDL， LDL） and the levels of MMP-2， MMP-9， TIMP-2 and TGF-β were compared among those groups. RESULTS： Before treatment， there was no statistical significance in above indexes among 3 groups （P＞0.05）. After treatment， 24 h urinary protein， Scr and TC levels of group A were still higher than normal level， while other lipid metabolism indexes were within normal range. 24 h urinary protein and TC level of group B were still higher than normal level， while Scr level was near the upper limit of the normal range， and other lipid metabolism indicators were within the normal range. Renal function indexes and lipid metabolism indexes of group C were within normal range， while renal function indexes levels of it were lower than those of group B （P＜0.05）； there was no statistical significance in lipid metabolism indexes， compared with group B （P＞0.05）. Compared with before treatment， TGF-β level of group A was significantly increased （P＜0.05）； there was no statistical significance in MMP-2， MMP-9 or TIMP-2 levels （P＞0.05）. TGF-β level of group B and group C was increased significantly （P＜0.05）， while the levels of MMP-2， MMP-9 and TIMP-2 were decreased significantly （P＜0.05）. CONCLUSIONS： Tacrolimus combined with valsartan can effectively delay renal dysfunction and improve lipid metabolism in CAD patients. The mechanism may be related to the inhibition of TIMP-2， MMP-2， MMP-9 and TGF-β expression.

Value of podocalyxin levels in urinary extracellular vesicles for diagnosis of diabetic nephropathy / 南方医科大学学报

<p><b>OBJECTIVE</b>To explore the value of detecting podocalyxin (PCX) level in urinary extracellular vesicles for the diagnosis of diabetic nephropathy.</p><p><b>METHODS</b>This study was conducted among 57 diabetic patients admitted during the period from March to September, 2017, including 34 with uncomplicated diabetics and 23 with diabetic nephropathy; 21 patients with other types of nephropathy and 11 healthy individuals were also included to serve as the controls. Transmission electron microscopy (TEM) and nanoparticle tracking analysis (NTA) were used to verify the separation of urinary extracellular vesicles. The molecular markers of extracellular vesicles (TSG101 and podocalyxin [PCX]) were detected using Western blotting. PCX levels in extracellular vesicles were also detected using ELISA.</p><p><b>RESULTS</b>TEM reveal the presence of numerous extracellular vesicles in the urine with intact morphology and different sizes, and most of them were below 300 nm in diameter as shown by NTA. TSG101 expression was detected in the samples from all the 4 groups. Positive expression of PCX was detected in the samples from patients with diabetic nephropathy but not in the other groups. In patients with diabetic nephropathy, the mean PCX levels (3.27±2.30 ng/μmol)was significantly higher than those in the healthy control group (1.22±0.36 ng/μmol), uncomplicated diabetes group (2.22±1.29 ng/μmol) and nephropathy group (1.24±0.45 ng/μmol).</p><p><b>CONCLUSIONS</b>PCX level in urinary extracellular vesicles is significantly increased in patients with diabetic nephropathy, suggesting the value of PCX as a potential marker for clinical diagnosis of diabetic nephropathy.</p>

Quantification and size distribution of 24-hour urinary extracellular vesicles from healthy adults / 南方医科大学学报

<p><b>OBJECTIVE</b>To analyze the quantity and size distribution of 24-hour urinary extracellular vesicles (uEVs) from healthy adults.</p><p><b>METHODS</b>The 24-hour uEVs from 9 healthy adults were isolated by hydrostatic filtration dialysis (HFD). The effectiveness of uEVs enrichment was evaluated using Western blotting and transmission electron microscopy (TEM). The quantity and size distribution of the uEVs was analyzed with BCA protein quantification, TEM, and nanoparticle tracking analysis (NTA).</p><p><b>RESULTS</b>uEVs with different sizes and morphologies were observed under TEM. Western blotting confirmed the expression of TSG101 in all the uEV fractions from the 9 donors, ranging from 132.50 to 760.70 ng/mL. NTA results showed that the number of 24-hour uEVs amount ranged from 3.56 × 10¹² particles to 5.12 × 10¹² particles, with a CV of 14.23%. The proportion of the vesicles with a diameter <40 nm was 0.04%-0.69% with a number range of (1.80-26.49)× 10⁹ particles; the proportion of vesicles with a diameter of 40-100 nm (which is consistent with the size of exosomes)was 22.07%-42.08% with a number range of (1.00-1.77)× 10¹² particles. The proportion of vesicles with a diameter of 100-1000 nm (consistent with the size of microvesicles) was 57.88%-77.85% with a number range of (2.09-3.86)× 10¹² particles.</p><p><b>CONCLUSION</b>The established HFD method allows efficient and convenient isolation of uEVs from a large amount of urine samples. The 24-hour uEVs from healthy adults show narrow differences between individuals and thus can be an ideal source of samples for relevant studies.</p>

Value of serum IgA/C3 ratio in the diagnosis of IgA nephropathy and its correlation with the clinicopathological features / 南方医科大学学报

<p><b>OBJECTIVE</b>To investigate the value of serum IgA/C3 ratio in the diagnosis of IgA nephropathy and explore its relationship with the clinicopathological features of the patients.</p><p><b>METHODS</b>Sixty-six patients with IgA nephropathy, 111 with other glomerular diseases, and 40 healthy control subjects without kidney disease were tested for serum IgA and C3 levels using CRM470 adjusted standardized immune turbidimetric method, and the IgA/C3 ratio was calculated. According to Oxford and Lee's classification criteria, we analyzed the pathological grades of the renal biopsy samples from patients with IgA nephropathy. The ROC curve was used to assess the value of serum IgA and IgA/C3 ratio in predicting IgA nephropathy.</p><p><b>RESULTS</b>Patients with IgA nephropathy had an elevated serum IgA/C3 ratio than those with other glomerular diseases and the control subjects, with an area under the ROC curve of 0.776. An elevated serum IgA/C3 ratio was not found to significantly correlate with the pathological grade of renal biopsy samples in patients with IgA nephropathy.</p><p><b>CONCLUSION</b>In the absence of renal biopsy findings, serum IgA/C3 ratio can help in the diagnosis of IgA nephropathy.</p>

Protective effect of diphenyleneiodonium, a NADPH oxidase inhibitor, on hyperpermeability of endothelial cells exposed to AOPP-HSA in vitro / 中国病理生理杂志

[ ABSTRACT ] AIM: To investigate the effect of advanced oxidation protein product-human serum albumin ( AOPP-HSA) at different concentrations on the permeability of human umbilical vein endothelial cell ( HUVEC) monolayer and the protective effect of NADPH oxidase inhibitor diphenyleneiodonium ( DPI ) against AOPP-HSA exposure. METHODS: Cultured HUVECs were exposed to 200 mg/L HSA (control) or AOPP-HSA (50, 100 and 200 mg/L).The permeability of the endothelial monolayer was assessed by measuring CMFDA-labeled THP-1 cells across the endothelial cells.The cultured HUVECs were treated with HSA (200 mg/L), AOPP-HSA (200 mg/L), or AOPP-HSA (200 mg/L)+DPI (100 μmol/L), and the activation of NADPH oxidase, endothelial monolayer permeability and cytoskeleton rear-rangement were evaluated.RESULTS: AOPP-HSA increased the permeability of the endothelial cell monolayer, and AOPP-HSA at 200 mg/L significantly increased the phosphorylation level of NADPH oxidase in the cells.Treatment with 100 μmol/L DPI obviously attenuated AOPP-HSA-induced NADPH oxidase activation, the increase in the permeability of the cell monolayer and the cytoskeleton rearrangement.CONCLUSION: AOPP-HSA increases the hyperpermeability of HUVEC monolayer via the phosphorylation of NADPH oxidase, and the NADPH oxidase inhibitor DPI reverses such effects.

Detection of serum food specific antibodies of 6 common foods in patients with IgA nephropathy / 南方医科大学学报

<p><b>OBJECTIVE</b>To explore the relationship between the major allergens of 6 common allergic foods and IgA nephropathy.</p><p><b>METHODS</b>A sensitive sandwich enzyme-linked immunosorbent assay (ELISA) was used to detect the serum levels of food-specific IgA1, IgG and IgE in 31 patients with IgA nephropathy and 80 healthy volunteers. All the patients were examined for a history of food allergy using a questionnaire.</p><p><b>RESULTS</b>Serum levels of IgA1 and IgG against the major allergens of the 6 common allergic foods were significantly higher in patients with IgA nephropathy than in healthy volunteers (P<0.05). There was no detectable food-specific IgE antibodies in the two groups. No patients had a clear history of food allergy. All the patients with increased IgG levels specific to 4 or more foods simultaneously had proteinuria.</p><p><b>CONCLUSIONS</b>Some foods especially the highly allergic ones may participate in the pathogenesis and progression of IgA nephropathy.</p>

The relationship between IgA nephropathy and low molecular weight urinary protein / 重庆医学

Objective To investigate the relationship among urinary protein molecular weight of IgA nephropathy ,renal tubu‐lointerstitium damage and clinical index ,and discuss the role of low molecular weight urinary protein in the mechanism of IgA pro‐gression .Methods A total of 34 patients with biopsy proven IgAN were studied .We detect the molecular weight of urinary protein by SDS‐PAGE .Data were processed with the classes of tubulointerstitial lesions and laboratory tests such as 24h urinary protein quantitation and serum creatinine(Scr) .Results The urinary protein were divided into four types according the SDS‐PAGE:the ball urinary protein group ,physiologic urinary protein group ,23 × 103 proteinuria group and 10 × 103 proteinuria group .Scores of tubu‐lointerstitial lesions ,twenty four hour urine protein quantitation and Scr level were all significantly higher in 10 × 103 proteinuria group than 23 × 103 proteinuria group (P<0 .05) .Conclusion 10 × 103 proteinuria may have close relationship with the progression of IgAN ,and it may be a useful index for the degree of tubulointerstitial lesions of IgAN .

Comparison of two equations for calculating glomerular filtration rate in evaluation of the prevalence of chronic kidney disease in healthy population / 南方医科大学学报

<p><b>OBJECTIVE</b>To compare two equations for calculating glomerular filtration rate (GFR) in the evaluation of the prevalence of chronic kidney disease (CKD) and the risk factors of CKD in urban healthy population.</p><p><b>METHODS</b>A total of 40377 subjects (24164 males and 16213 females) participated in this study. Body height, weight and blood pressure were measured, and morning urine and venous blood samples were collected for routine urine and blood tests with measurements of blood glucose, total cholesterol, high density lipoprotein (HDL), low-density lipoprotein (LDL), creatinine and uric acid.</p><p><b>RESULTS AND CONCLUSION</b>Using Japanese CKD Epidemiology Collaboration (J-EPI) equation and Chinese modified Modification of Diet in Renal Disease (C-MDRD) equation, the prevalence of CKD calculated was 3.9% and 6.3% in this population, respectively. The independent risk factors of CKD included an age over 60 years, high uric acid, and high blood glucose.</p>

Role and mechanism of phosphate myosin light chain in chronic allograft nephropathy of rats / 中华器官移植杂志

Objective To investigate the role and mechanism of phosphate myosin light chain (pMLC) in the rat kidney of chronic allograft nephropathy (CAN) model. Methods The left donor kidneys from Fisher (F344) rats were orthotopically transplanted into Lewis recipients. Meanwhile, the F344 rats and LEW rats with resection of the right kidney served as control groups. Animals were harvested respectively at the 4th, 8th and 12th week after transplantation. The creatinine clearance rate (CCr) was calculated by urine creatinine of 24-h urine. Blood samples were collected from rats for determination of serum creatinine. The expression of pMLC was detected by using Western blotting and immunohistochernistry, and that of integrin-linked kinase (ILK) by using immunohistochemistry. Results Mononuclear cells infiltration of allografts was markedly aggravated as compared to the controls. Allografts got severe interstitial fibrosis and tubular atrophy at 12th week after transplantation. The expression of pMILC and ILK was up-regulated in the kidney of CAN rats after transplantation, and increased more significantly as the time went on. The expression of pMILC was significantly correlated with 24-h urine protein excretion (r= 0. 273, P＜0. 05), serum creatinine levels (r = 0. 434, P＜0. 01 ), the number of tubulointerstitial infiltrated mononuclear cells (r = 0. 525, P＜0. 01 ), the number of smooth muscle cells (SMC) in vascular wall (r= 0. 676, P＜0. 01 ) and the extent of interstitial fibrosis (r= 0. 570, P＜0. 01 ).There was a significantly positive correlation between ILK and pMLC in CAN rats at the 4th week after transplantation (r= 0. 778, P＜0. 01 ). Conclusion pMLC might play an key role in CAN, and the over-expression of ILK might be involve in the pathogenesis of CAN.

An epidemiological study on the prevalence of hyperuricemia and its relationship to chronic kidney disease in the urban community residents of Guangxi / 中华内分泌代谢杂志

Objective To detect the prevalence of hyperuricemia and its relationship to chronic kidney disease(CKD) in the residents of Guangxi, and to discuss the risk factors for the hyperuricemia associated renal damage. Methods The residents aged 18-75 years old(n=6 273) in Xiangshan community,Guilin, were screened by means of cross-sectional study. Blood pressure was measured at 8:00-9:00.Fasting blood and urine samples were collected to determine blood glucose, lipid, insulin, creatinine, and urine albumin. Results The prevalence of hyperuricemia in the community residents was 23.5% in all cohort, being significantly higher in male residents than in female(28.4% vs 19.7%,P＜0.01). The prevalence of CKD was 21.6% in all cohort, and was 24.9% in males and 19.0% in females(P＜0.01). The prevalence of CKD was 30.4% and 18.9% respectively in residents with and without hyperuricemia(P＜0.01).The prevalence of CKD in males with hyperuricemia(34.3%) was significantly higher than in males without hyperuricemia(21.2%) and females with hyperuricemia(25.9%, all P＜0.01). CKD was only positively related to low-density lipoprotein cholesterol, blood glucose, and systolic blood pressure shown by logistic regression analysis. Conclusions The prevalence of hyperuricemia markedly increases in the urban residents, which contribute to the raised prevalence of CKD. Slightly elevated blood uric acid level is associated with raised prevalence of CKD.

Role of glucogen synthase kinase-3β in a rat kidney model of chronic allograft nephropathy / 中华器官移植杂志

Objective To investigate the expression and significance of glucogen synthase kinase-3β (GSK-3β) in the pathogenesis of chronic allograft nephropathy (CAN) in rats.Methods Kidneys of Fisher (F344) rats as donors were orthotopically transplanted into Lewis (LEW) rats as recipients.The renal function and histopathological changes were observed at 4,8,12,16,and 24week post-transplantation.Phosphorylated GSK-3β (p-GSK-3β) protein and mRNA expression was determined by using immunohistological assays and RT-PCR respectively.Results Our data showed that 24-h urinary protein excretion in CAN rats was increased significantly at week 16 as compared with F344/LEW controls.Allografts showed markedly increased mononuclear cells infiltration and presented with severe interstitial fibrosis and tubular atrophy at 16 and 24 week post-transplantation.p-GSK-3β expression (protein/mRNA) was down-regulated in rat kidneys with CAN,and the decrease became more significant over time after transplantation.p-GSK-3β expression was correlated significantly with 24-h urinary protein excretion,serum creatinine levels,tubulointerstitial mononuclear cells infiltration,smooth muscle cells migration in vascular wall,and interstitial fibrosis.Conclusion It was concluded that GSK-3β down-regulation was the key event that may be involved in mononuclear cells infiltration and vascular SMCs migration at early stage,and interstitial fibrosis and allograft nephroangiosclerosis at later stage of CAN pathogenesis in rats.

Influence of hyperuricemia on long-term renal allograft function after renal transplantation Is it a factor of chronic renal allograft dysfunction ? / 中国组织工程研究

BACKGROUND: A large number of researches have confirmed that hypertension, vascular nephrosclerosis and chronic systemic inflammatorome were the importance factors of chronic allograft dysfunction. Hyperuricemia is associated with primary hypertension and vascular nephrosclerosis, and can result in chronic systemic inflammatorome, but it was uncertain whether post-transplantation hyperuricemia and its lesion influence the long term graft function. OBJECTIVE: To investigate the prevalence of hyperuricemia in renal transplant recipients (RTRs) before and after transplantation and the influence of hyperuricemia on long term graft function. METHODS: A total of 216 renal transplant recipients [146 males with the mean age of (40.98±11.09) years and 70 females with mean age of (40.01±11.62) years]with normal renal function after transplantation were selected from PLA Center of Kidney Transplantation and Dialysis, the 181 Hospital of Chinese PLA. In order to compare the influence of different hyperuricemia status on the long term graft function, the patients were divided into 4 groups according their pre-transplant baseline and post-transplant serum uric acid (SUA) levels, SUA normal group, pre-transplant high SUA group, post-transplant high SUA group and both pre-transplant and post-transplant high SUA group. The patients were also divided into 3 groups according to their post-transplantation SUA level to study the influence of SUA on the long term graft function, normal SUA group, hyperuricemia (SUA < 500 μmol/L) group and hyperuricemia (SUA > 500 μmol/L) group. Effects of hyperuricemia and SUA levels pre-and post-transplantation on long term graft function were observed. RESULTS AND CONCLUSION: Hyperuricemia existed in 34.2% male RTRs and 37.7% females before transplantation, while it existed in 36.2% male RTRs and 42.4% females at the first month post-transplantation when they had normal Scr levels. The incidence rate of post-transplant hyperuricemia in female RTRs was significantly higher than male RTRs (P < 0.05). The average post-transplantation SUA levels in both male and female RTRs were significantly higher than those before transplantation (P < 0.01). At follow-up end, the pre-transplantation SUA levels did not significantly influence on the long term graft function (P > 0.05), meanwhile the RTRs with continuous post-transplant hyperuricimia had poorer long term graft function than those with normal post-transplantation SUA levels. It is indicated that hyperuricemia is more common in post-transplantation recipients, especially in female RTRs, when compared to pre-transplantation, and post-transplantation hyperuricemia often existed in renal transplant recipients with normal graft function. Furthermore it is suggested that post-transplantation hyperuricimia, but not pre-transpiantation hyperuricemia, could also act as a factor inducing chronic renal allograft dysfunction.

Clinical study on the risk factors of insulin-resistance and its relationship with metabolic syndrome after kidney transplantation / 中华器官移植杂志

Objective To investigate the risk factors of insulin resistance(IR)and its relationship with metabolic syndrome in patients after lenal transplantation.Methods 133 renal transplant redpients who had not undergone acute rejection,calcinurine intoxication and severe infection,and had normal renal function and no proteinuria at the 6th month post-transplantation,were involved in the study.They had a history of chronic glomerulonephritis as the primary disease of ESRF but rio diabetes mellitus.108 recipients(CsA group)were treated with CsA,mycophenolate mofetil(MMF)and prednisone after transplantation,19 recipients(Tac group)with tacrolimns(Tac),MMF and prednimne,and 6 recipients with Simlimus,respectively.One year later,blood and urine biochemical tests and physical examinations were performed on the recipients,and HOMA calculated.200 cormnunity residents were randomly selected as controls.Results The incidence of MS in the recipients was 33.1%,significantly higher than controls(15.0%).There was no significant difference in the incidence of obesity and overweight between recipients(29.3%)and controls(37.5%).In recipients with obesity or overweight,the insulin-resistance level and urine albumin level,and the incidence of MS weree significantly higher than those without obesity or overweight.The insulin-resistance level in Tac-treated recipients was markedly higher than CsA-treated recipients,and there was a positive correlation between the blood concentration of Tac and insulin-resistance levd.Microalbuminufia-positive recipients had higher insulin-resistance levels.Metabolic syndrome-complicating recipients had higher insulin-resistance levels than those without metabolic synawme,and higher insulinresistance levels existed in recipients with hypertriglyceridemia or hyperchcllesterolemia,hypertension.Conclusion Obesity or overweight,Tac(especially when blood concentration was higher)were risk factors resulting in imulin-resistanee in kidney transplant recipients.It is suggested that insulin-resistance might be involved in the pathogenesis of metabolic syndrome including hypertrglyceridmaia,hypercbolestemlemia and hypertenion.

Influence of post-transplantation hyperuricemia on the late function of renal allografts / 解放军医学杂志

0.05).But its incidence was higher in females than in males after transplantation(P

Role of biopsy of kidney allograft in early diagnosis and differential diagnosis of renal allograft diseases / 解放军医学杂志

Objective To investigate the role of biopsy kidney allograft in the early diagnosis and differential diagnosis of acute and chronic rejection and other diseases involving renal allograft,and to determine the optimal time for early biopsy in chronic allograft rejection.Methods Non-random biopsy of renal allograft was performed in 44 kidney transplant recipients with the clinical manifestation of diagnosis-unconfirmed allograft diseases,in the presence increased in serum creatinine,microalbuminuria or/and proteinuria,glomerular hematuria and so on.Another 6 kidney transplant recipients received routine allograft biopsy 1 month after operation.Pathological evaluation was performed in all sections according to Banff 97 classification and based on clinical data.Results Chronic allograft rejection was discovered in the renal allograft specimens of 31.3%,76.5% and 88.2% recipients,respectively,in the 1st year,the 2nd to 3rd year and over 3 years after operation,and most of them showed no obvious clinical manifestation.A part of recipients with clinical diagnosis of acute rejection also showed pathological manifestations of chronic rejection and/or glomerulonephritis and chronic cyclosporine nephropathy.A part of recipients with clinical diagnosis of chronic rejection showed pathological manifestations of acute rejection and/or glomerulonephritis and chronic cyclosporine nephropathy.Pathological features of acute or chronic rejection,glomerulonephritis and chronic cyclosporine nephropathy were observed respectively in recipients with disorders of kidney allograft with unknown diagnosis.No obvious clinical symptoms were observed in nearly half of the patients with pathological diagnosis of glomerulonephritis.Good therapeutic effect was obtained in these recipients who were correctly treated on the basis of definite pathological diagnosis.Conclusions It is indicated that optimal time for early diagnosis in chronic renal allograft rejection might be the 2nd and 3rd year after transplantation,and routine biopsy should be performed in this period.It is suggested that biopsy of renal allograft is of importance value for rectification of clinical diagnosis and for recipients with clinically undefined renal allograft diseases.It is also indicated that there might be coexistence of acute,chronic rejection and/or glomerulonephritis and chronic cyclosporine nephropathy.

The effects of EPO on immunofunctions in patients with chronic renal failure / 中国免疫学杂志

Objective:To investigate the effect of EPO on humoral and cellular immunity and the monocyte antigen presenting function in patients with chronic renal failure(CRF).Methods:60 patients with CRF were divided into three groups.Group A patients accepted hemodialysis and treated with EPO.Group B patients treated with EPO and didn't accept hemodialysis.Group C patients didn't accept EPO treatment and hemodialysis.After 8 weeks treatment,the subpopulations of T lymphocyte were analyzed with detected by flow cytometry analysis method;Immunoglobulins were measured with radioactive immuntzation method.In addition,the infection rate of patients with CRF in every group was compared.Results:The parameters of immune functions of patients with CRF were comparable between groups before treatment.After treated with EPO for 8 weeks,RBC numbers and Hb were significantly increased in patients of group A and group B,but not in patients of group C.IgG and IgA were increased in patients of groups A and groups B and have statistic differences as compared with that in patients of group C(P

The prognostic value of clinical and pathological findings in lupus nephritis / 中华风湿病学杂志

3 on biopsy contributed significantly to the prognostic value of RSR,and the presence of tubular atrophy was associated with decreased both SR and RSR.Conclusion These results indicate that early diagnosis is significantly associated with increased SR and RSR.Cr and 24UP are independent indicators of prognosis in clinical respect.Chronic renal histological features and renal artery lesion serve an additional important role in the assessment of prognosis in patients with LN.

Study of signaling pathway of LDL and oxLDL inducing kidney tubular epithelial cells transdifferentiation / 中华肾脏病杂志

Objective To explore whether LDL and oxLDL may induce kidney tubular epithelial-mesenchymal transition (EMT) and its mechanism. Methods The second generation human kidney tubular epithelial cells (TECs) were cultured for 24 hours in different conditions as (1) serum free as control, (2) treated with LDL (50 ?g/ml) , (3) treated with oxLDL(50 ?g/ml), (4) treated with LDL(50 ?g/ml) plus PD98059(5 ?mlo/L) , (5) treated with oxLDL(50 ?g/ml) plus PD98059 (5 ?mol/L). The expression of cytokeratin, E-cadherin, ?-SMA and vimentin was assessed by immunofluorescence and Western-blot. Western-blot was also performed to test the expression of collagen I and phospho-ERKl/2MAPK and phospho-GSK-3?. Results oxLDL was more potently in inducing tubular EMT than LDL at 24 hours as demonstrated by de novo a-SMA expression, increased expression of vimentin, partial loss of cytokeratin and reduction of E-cadherin expression by TECs. The expression of collagen I and phospho-ERKl/2MAPK and phospho-GSK-3? was increased in TECs stimulated by LDL or oxLDL. MAPK inhibitor (PD98059) inhibited the phosphorylation of GSK-3P and almost completely blocked oxLDL-induced tubular EMT. However, PD98059 alone was able to inhibit LDL-induced tubular EMT partially. Conclusions oxLDL is more potently in inducing tubular EMT than LDL. The ERKl/2MAPK-GSK-3? signaling pathway mediates the LDL or oxLDL-induced tubular EMT.

Expression and significance of MCP-1 and RANTES in renal tissue of chronic allograft nephropathy / 中华器官移植杂志

Objective To investigate the expression of monocyte chemoattractant protein 1 (MCP-1) and RANTES and their significance in the pathogenesis of chronic allograft nephropathy.Methods Uninephrectomized F344 rats and LEW rats were used as control animals. Left renal transplantation LEW rats were used as experimental animals. Twelve weeks after transplantation, the renal function and the histological disorders of chronic allograft nephropathy were studied. The expression of MCP-1 and RANTES in the allografts was detected by immunohistochemistry.Results Compared with F344 control groups, the serum creatitine level ( 96.200 ? 36.405 ) ?mol/L in the experimental groups was increased ( P