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Objective:To investigate the clinicopathological characteristics and influencing factors of kidney prognosis in primary IgA nephropathy (IgAN) patients.Methods:The data of primary IgAN patients diagnosed with renal biopsy in the First Affiliated Hospital of Anhui Medical University from January 2015 to September 2019 were retrospective analyzed. According to the level of baseline estimated glomerular filtration rate (eGFR) when performing renal biopsy, the patients were divided into group A[eGFR≥90 ml·min -1·(1.73 m 2) -1], group B[eGFR 61-89 ml·min -1·(1.73 m 2) -1] and group C[eGFR≤60 ml·min -1·(1.73 m 2) -1]. The clinical and pathological data were collected and compared among the three groups. Kaplan-Meier method was conducted for renal results, whereas the Cox proportional-hazards regression model was exploited to analyze the influencing factors of kidney prognosis in IgAN patients. Results:A total of 742 patients were included in the study, including 394 cases (53.1%) in group A, 203 cases (27.4%) in group B, and 145 cases (19.5%) in group C. There were 325 males (43.8%) and 417 females (56.2%). The median duration of renal biopsy was 6 (1, 24) months, and the median age was 36 years old (18-68 years old). As the baseline level of renal function decreased, the proportion of patients with nephrotic syndrome, hypertension, anemia and hyperuricemia and the levels of 24 h urinary protein, serum triglyceride and total cholesterol increased significantly (all P<0.05), while the proportion of gross hematuria episodes and the ratio of serum albumin to globulin significantly decreased (all P<0.05). For the aspect of pathological manifestations, the proportions of cell proliferation in capillaries (E1), segmental sclerosis or adhesion (S1), renal tubular atrophy or interstitial fibrosis (T1/2), globular sclerosis, renal arteriole wall thickening and vitreous degeneration, Lee's grade Ⅳ and Ⅴ increased with the decrease of baseline renal function (all P<0.05). Kaplan-Meier analysis showed that the cumulative renal survival rate decreased with the decline of baseline renal function (Log-rank χ2=88.510, P<0.001). As a result of multivariate Cox regression analysis, nephrotic syndrome ( HR=2.399, 95% CI 1.054-5.459, P=0.037), hypertension ( HR=1.806, 95% CI 1.071-3.048, P=0.027), low baseline eGFR (taking group A as the reference, group B: HR=2.383, 95% CI 1.053-5.392, P=0.037; group C: HR=6.878, 95% CI 3.074-15.393, P<0.001), IgG deposition ( HR=2.224, 95% CI 1.384-3.574, P=0.001) and globular sclerosis ( HR=2.075, 95% CI 1.230-3.501, P=0.006) were the independent influencing factors for renal progression in primary IgAN patients. Conclusions:The level of baseline renal function in primary IgAN patients can be used to predict the extent of clinic-pathological damage. Nephrotic syndrome, hypertension, low baseline eGFR, IgG deposition and globular sclerosis are the independent influencing factors for renal progression in primary IgAN patients.
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Objective@#To investigate whether Bruton's tyrosine kinase knockout (Btk-/-) in macrophages attenuates diabetic kidney disease in the streptozotocin (STZ)-induced mice.@*Methods@#Macrophages-specific Btk-/- mice and control mice (C57BL/6N) were randomly divided into WT group, diabetic group, Btk-/- group and Btk-/- diabetic group. The diabetic models were induced by STZ (50 mg/kg). After 12 weeks, relevant biochemical parameters and the histological changes of kidneys were detected. The expression of macrophages marker CD68 were detected by immunofluorescence, and the immunohistochemistry was employed to detect the expression of WT1 and Nephrin on renal podocytes. In addition, the expression of fibronectin (FN), collagen type IV (IV-Col), transforming growth factor-β1 (TGF-β1), iNOS, phospho (p)-Btk, interleukin-1β (IL-1β), tumor necrosis factor-α (TNF-α), MAPK and NF-κB signaling pathway were detected by Western blotting. RT-PCR was used to detect the mRNA of IL-1β, TNF-α and monocyte chemotactic protein-1 (MCP-1).@*Results@#Compared with diabetic group, the mice in Btk-/- diabetic group had reduced albuminuria and attenuated kidney histopathology significantly, significantly increased WT1 and Nephrin, significantly decreased expression of CD68, FN, IV-Col and TGF-β1, and these changes were correlated with decreased of renal inflammatory cytokines such as IL-1β, TNF-α, MCP-1 and down-regulating MAPK and NF-κB signaling pathway (all P<0.05).@*Conclusion@#Macrophages-specific Btk-/- may protect the kidney of diabetic mice by reducing the expression of renal inflammatory cytokines in MAPK and NF-κB signaling pathway.
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Objective:To investigate whether Bruton's tyrosine kinase knockout (Btk -/-) in macrophages attenuates diabetic kidney disease in the streptozotocin (STZ)-induced mice. Methods:Macrophages-specific Btk -/- mice and control mice (C57BL/6N) were randomly divided into WT group, diabetic group, Btk -/- group and Btk -/- diabetic group. The diabetic models were induced by STZ (50 mg/kg). After 12 weeks, relevant biochemical parameters and the histological changes of kidneys were detected. The expression of macrophages marker CD68 were detected by immunofluorescence, and the immunohistochemistry was employed to detect the expression of WT1 and Nephrin on renal podocytes. In addition, the expression of fibronectin (FN), collagen type IV (IV-Col), transforming growth factor-β1 (TGF-β1), iNOS, phospho (p)-Btk, interleukin-1β (IL-1β), tumor necrosis factor-α (TNF-α), MAPK and NF-κB signaling pathway were detected by Western blotting. RT-PCR was used to detect the mRNA of IL-1β, TNF-α and monocyte chemotactic protein-1 (MCP-1). Results:Compared with diabetic group, the mice in Btk -/- diabetic group had reduced albuminuria and attenuated kidney histopathology significantly, significantly increased WT1 and Nephrin, significantly decreased expression of CD68, FN, IV-Col and TGF-β1, and these changes were correlated with decreased of renal inflammatory cytokines such as IL-1β, TNF-α, MCP-1 and down-regulating MAPK and NF-κB signaling pathway (all P<0.05). Conclusion:Macrophages-specific Btk -/- may protect the kidney of diabetic mice by reducing the expression of renal inflammatory cytokines in MAPK and NF-κB signaling pathway.
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Objective To investigate effects of melatonin (MT) on high glucose-induced cell proliferation,Toll-like receptor 4 (TLR4) signaling pathway and expressions of inflammatory factor in mouse mesangial cells (SV40).Methods SV40 cells were divided into mannitol control group (30 mmol/L mannitol),normal control group (5 mmol/L glucose),control (5 mmol/L glucose)+ 1000 μmol/LMT group,high glucose group (25 mmogL glucose),high glucose +10,100,1000 μmol/L MT group and high glucose + TLR4 inhibitor (TAK242) group.(1) The cell viability was measured by CCK-8 cytotoxicity kits,and cell proliferation was measured by EdU kits.The expression of TLR4 and the nuclear translocation of nuclear factor-κB (NF-κB p65) were observed by immunofluorescence.(2) Realtime quantitative PCR was used to detect TLR4 mRNA expression.Real-time quantitative PCR and ELISA were used to determine the mRNA and protein secretion levels of the downstream inflammatory factors,such as monocyte chemoattractant-1 (MCP-1),interleukin-1β (IL-1β) and tumor necrosis factor of α (TNF-α);Western blotting was used to detect TLR4 pathway proteins,such as TLR4,myeloid differentiation factor 88 (MyD88),β interferon TIR domain adaptor (Trif),phosphorylated interferon regulatory factor 3 (p-IRF3) and phosphorylated NF-κB inhibitory protein (p-IκB).Results High glucose stimulated mesangial cell proliferation,promoted TLR4 expression and NF-κB p65 transcription activity.Both MT and TAK242 inhibited the above reactions,and the effects of MT was concentration-dependent.Compared with the normal control group,high glucose group had up-regulated expressions of TLR4,MCP-1,IL-1β and TNF-α mRNA (all P ＜ 0.05),but also significantly increased the protein expressions of MyD88,Trif,p-IRF3 and p-IκB (all P ＜ 0.05).Compared with those in the high glucose group,the expression of TLR4 was down-regulated in the high glucose+ 10,100,1000 μmol/L MT group and the high glucose+TAK242 group (all P ＜ 0.05),while the expressions of MyD88,Trif,p-IRF3,p-IκB,MCP-1,IL-1β and TNF-α decreased (all P ＜ 0.05).The effects of MT was concentration-dependent.Conclusions High glucose stimulates the proliferation of SV40,and MT can inhibit the proliferation of mesangial cells and the expressions of inflammatory factors through TLR4 signaling pathway.
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Objective To investigate the role and mechanism of macrophage activation induced by exosomes from high glucose-treated renal tubular epithelial cells.Methods (1) The supernatant of renal tubular epithelial cells which were cultured in normal glucose control group (5.5 mmol/L D-glucose) or high glucose group (30.0 mmol/L D-glucose) for 48 h were collected and ultracentrifuged to harvest exosomes.Exosomes were identified by transmission electron microscope and Western blotting.(2) Exosomes were labeled with the green lipophilic fluorescent dye PKH67 and cultured with THP-1 macrophage to investigate whether HK2-derived exosomes could be internalized by THP-1 macrophage.Observing the morphology microscopically and detecting the chemotaxis function of THP-1 macrophages in Transwell chamber after co-cultured with exosomes.The expression of inducible nitric oxide synthase (iNOS),tumor necrosis factor-α (TNF-α),Interleukin-1β (IL-1β),monocyte chemoattractant protein-1 (MCP-1) in cells and supernatants were separately detected by quantitative Real-time PCR (qRT-PCR) and enzyme linked immunosorbent assay (ELISA),and the expression of p-c-Jun NH2-terminal kinase (p-JNK),mitogen-activated protein kinase p-p38 (p-p38MAPK) and nuclear factor κB p65 (NF-κB p65) in THP-1 macrophages were detected by Western blot.Results (1) Vesicles that harvested by ultracentrifugation ranged in size from 30 nm to 100 nm and expressed exosomal marker CD63,TSG101 but absence of calnexin which is a marker of endoplasmic reticulum,suggesting that the exosomes were not contaminated with cells.(2) Results from laser scanning confocal microscope showed that each group of exosomes can be internalized by THP-1 macrophages.Compared with normal glucose exosomes group,high glucose exosomes had increased the expression of iNOS,TNF-α,IL-1β and MCP-1 in THP-1 macrophages (all P ＜ 0.01),moreover,p-JNK,p-p38 MAPK and NF-κB p65 proteins level also increased significantly (all P ＜ 0.01).Conclusions Exosomes from high glucose-treated HK2 cells can induce THP-1 macrophage activation and functional changes through MAPK/NF-κB pathway.
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Aim To investigate the effect of paeoniflorin(PF)on TLR2/4 pathway in AGEs-induced RAW264.7 macrophages.Methods RAW264.7 macrophages were incubated at different time points in AGEs stimulation,as well as different concentrations of PF,to optimize experimental conditions.RAW264.7 macrophages were randomly divided into five groups: control group(DMEM),bull serum albumin(BSA)group(200 mg·L-1 BSA),AGEs group(200 mg·L-1 AGEs),paeoniflorin group(200 mg·L-1 AGEs+10-5 mol·L-1 PF)and TLR2/4 inhibitor group(200 mg·L-1 AGEs+30 mg·L-1 OxPAPC).The expression of Toll-like receptor 2(TLR2),Toll-like receptor 4(TLR4),myeloid differentiation factor 88(MyD88),p-IRAK1,TIR-domain containing adaptor protein-inducing IFN-β(TRIF),interferon regulatory factor 3(IRF3),p-IRF3,NF-κB p-p65,NF-κB p65,inducible nitric oxide synthase(iNOS),tumor necrosis factor-α(TNF-α),interleukin-l β(IL-1β)and monocyte chemotactic protein-1(MCP-1)were measured by Western blot.Real-time PCR was used to detect the expression of TLR2 and TLR4 mRNA,while TNF-α,IL-1β and MCP-1 levels in cell supernatant were measured by ELISA.Results Compared with control group,AGEs significantly increased the expression of TLR2,TLR4,MyD88,p-IRAK1,TRIF,IRF3,p-IRF3,NF-κB p-p65,NF-κB p65,iNOS,TNF-α,IL-1β and MCP-1 proteins(P<0.01),as well as TLR2 and TLR4 mRNA(P<0.01).TNF-α,IL-1β and MCP-1 contents were also elevated in cell supernatant(P<0.01).The effects induced by AGEs were decreased significantly in PF and TLR2/4 inhibitor group(P<0.01).Conclusion PF plays an anti-inflammatory effect via inhibiting TLR2/4 pathway on macrophages,which may provide a new theoretical basis for the treatment of diabetic nephropathy.
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Aim We used bone marrow-derived macro-phages ( BMMs ) , to explore the mechanism of macro-phage activation and the effect of TGF-β activated ki-nase-1 ( TAK1 ) inhibitor 5 Z-7-oxozeaenol on it under AGEs conditions. Methods The BMMs were obtained from C57 mice, and purity of BMMs was detected by flow cytometry. Cell viability was tested after treatment with different concentrations of TAK1 inhibitors. Laser confocal microscopy was used to detect macrophage M1 subtype . Flow cytometry was used to analyse the macro-phage activated by AGEs. TNF-α and MCP-1 mRNA levels were evaluated by qRT-PCR. Western blot was used to detect the expression levels of TAK1 signal pathway protein. Results AGEs stimulation could in-crese the activity of M1 macrophages,and 5Z-7-oxoze-aenol could inhibit the differentiation of BMMs. Com-pared with control group, AGEs increased the expres-sion of MCP-1 and TNF-α mRNA(P NF-κBp65 proteins ( P <0. 05 ) . Conclusions AGEs can induce BMMs to M1 phenotypic polarization. 5Z-7-oxozeaenol reduces the expression of inflammatory cyto-kine via inhibiting TAK1/MAPKs, MAPKs/NF-κB pathways.
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Objective To investigate the regulation of melatonin (MT) on Toll-like receptor 4 (TLR4) signaling in diabetic db/db mice kidneys.Methods The 48 10-week-old male db/db mice were randomly divided into db/db group,db/db+MT 50 μg/kg group,db/db+MT 100 μg/kg group and db/db+MT 200 μg/kg group,each consisting of 12 mice.These mice received i.p.injections of MT These mice received i.p.injections of MT [dissoved in phosphate buffer solution (PBS)/ dimethylsulfoxide (DMSO) solution,given every day].Alternatively,12 db/m mice served as the control group.db/m and db/db group were injected i.p.with the same volume of PBS/DMSO solution.The animals were sacrificed after 12 weeks of dosage administration.Blood glucose (BG),body weight (BW),kidney weight (KW) and 24 h urinary albumin excretion rate (UAER) were determined;Kidney pathological lesions were evaluated by renal pathological staining.Immunohistochemistry of renal TLR4,NF-κB p65,and ED-1 was performed to determine the immunoreactivity.Western blotting was used to detect the expression of renal TLR4,myeloid differentiation factor 88 (MyD88),TIR-domaincontaining adaptor inducing interferon-β (TRIF),interferon regulatory factor 3 (IRF-3) and NF-κB p65,while the mRNA expressions of renal tumor necrosis factor-α (TNF-α) and monocyte chemotactic protein-1 (MCP-1) were evaluated by real-time PCR.Results Compared with control group,the levels of BG,BW,KW and UAER were much higher in db/db mice group (P ＜ 0.01),while KW in db/db+MT (100,200 μg/kg) groups and UAER level in db/db+MT (50,100,200 μg/kg) groups were distinctly decreased compared with those in db/db group (P ＜ 0.01).In week 12 db/db mice,the glomerular mesangial expansion index and tubulointerstitial injury index were increased compared with those in db/m mice (P ＜ 0.01).The above kidney histopathologic lesions were distinctly ameliorated by 50,100,200 μg/kg MT (P ＜ 0.05).Immunohistochemistry intensity of renal TLR4,NF-κB p65 and ED-1 displayed obvious differences between db/m mice and db/db mice (P ＜ 0.01),and that were remarkably decreased in db/db+MT (50,100,200 μg/kg) mice compared with db/db mice (P ＜ 0.05).Western blotting showed that the protein expression of renal TLR4,MyD88,TRIF,IRF-3 and NF-κB p65 were stronger in db/db group compared with those in db/m group (P ＜ 0.05) and weaker in db/db+ MT (50,100,200 μg/kg) groups compared with those in db/db group (P ＜ 0.05).Futhermore,the mRNA expressions of renal MCP-1 and TNF-α were higher in db/db group compared with those in db/m group (P ＜ 0.01) and lower in db/db+MT (50,100,200 μg/kg) groups compared with those in db/db group (P ＜ 0.01).Conclusion Melatonin may partly down-regulate TLR4 signaling pathway to inhibit Inflammatory reaction and alleviate kidney injury in diabetic db/db mice.
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Objective To investigate the role of transforming growth factor-β activated kinase-1 (TAK1) signaling pathway in the activation of bone marrow derived macrophages (BMDM) induced by high glucose.Methods Purity of mouse BMDM was detected by flow cytometry.The mice macrophages cultured in vitro were stimulated by high glucose and treated with TAK1 specific inhibitor 5Z-7-oxozeaenol.Cells were divided into normal control group (RPMI 1640),osmolality control group (25 mmol/L mannitol),high glucose group (33 mmol/L D-glucose) and inhibitor group (33 mmol/L D-glucose+300 nmol/L 5Z-7-oxozeaenol).Immunocytochemistry and flow cytometry were used to detect macrophage subtype.The expression of monocyte chemotactic protein-1 (MCP-1) and tumor necrosis Factor-α (TNF-α) mRNA were determined by real time PCR.Expressions of p-TAK1,TAK1 binding protein (TAB1),p-JNK,p-p38 MAPK and NF-κB p65 proteins were analyzed by Western blotting.Results The purity of BMDM was about 99.36％.Compared with normal control group,high glucose group had increased percentage of M1 macrophages,increased expression of MCP-1 and TNF-α mRNA (all P ＜ 0.05).Moreover,p-TAK1,TAB1,p-JNK,p-p38 MAPK and NF-κB p65 proteins expression also increased significantly in high glucose group (all P ＜ 0.05).After treatment with inhibitor 5Z-7-oxozeaenol,the effects induced by high glucose were inhibited (P ＜ 0.05).Conclusions High glucose can induce M1 macrophage activation and expression of inflammatory cytokine of BMDM,which can be inhibited 5Z-7-oxozeaenol through inhibiting TAK1/MAPK and TAK1/NF-κB pathway.
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Objective]To summarize Professor Tan Zihu’s experience in treating vascular dementia. [Methods]Summarized“the awareness on the etiology and pathogenesis of vascular dementia”,the theory of“prevention of disease”,such as“preventing measure taken before the occurrence of disease”,“treatment characteristics”,and with 1 case for specific instruction. [Result]The responsibility of the etiology’s source of vascular dementia is spleen-kidney deficiency,closely linked to stroke.The basic pathogenesis is the deficiency of sea of marrow,which leads to the dysfunction of brain.He advocates the theory of“prevention of disease”,such as“preventing measure taken before the occurrence of disease”,the primary prevention for the ones who have the high risk factor for stroke,and the early findings,early diagnosis and early prevention of vascular dementia.[Conclusion]Professor Tan Zihu,an expert of TCM,treats vascular dementia starting with spleen-kidney deficiency,combining the theory of“prevention treatment of disease”.It gets good clinical effect with promotion value.
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Objective To discuss the expression of tumor necrosis factor-like weak inducer of apoptosis ( TWEAK) in serum, urine and renal tissue in lupus nephritis( LN) . Methods The serum and urine levels of TWEAK were assessed by ELISA in LN patients and normal controls. Immunohistochemistry was used to detect the expressions of TWEAK in the kidney of patients and healthy controls. Results The serum and urine concentrations of TWEAK and MCP-1 were significantly higher in LN patients than those in healthy controls(P<0. 01). In addition,the level of serum TWEAK showed positive correlation with SLEDAI and negative correlation with serum C3 level ( P <0. 01),the expression of urine TWEAK showed positive correlation with SLEDAI (P<0. 05). In healthy renal tis-sues TWEAK was distributed mainly in renal tubules and rarely seen in glomerular while the expressions of TWEAK increased in renal tubular and glomeruli stainings were found in LN paitients. TWEAK could induce increased mac-rophage migration, may be involved in the pathological progression of lupus nephritis. Conclusion TWEAK may play key roles in the pathogenesis of LN. Meanwhile, TWEAK in serum and urine may be useful as markers of dis-ease activity. The change of TWEAK maybe associated with the pathology category of LN.
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Objective To investigate the pathogens and their antibiotic resistance in patients with peritoneal dialysis‐related peritonitis .Methods The clinical data including pathogens ,antibiotic resistance profile of 213 patients with peritoneal dialysis‐related peritonitis who were treated in our peritoneal dialysis center from January 2011 to December 2013 were analyzed retrospectively .Results Dialysate culture was positive for 132 (62 .0% ) of the 213 cases ,resulting in a total of 140 strains of microorganisms ,including 84 strains of gram positive cocci ,37 strains of gram‐negative bacilli ,10 strains of fungus and 9 strains of gram positive bacilli . Coagulase‐negative Staphylococcus was the most common gram positive bacteria while Escherichia coli was the most common gram negative bacteria isolated from the effluent .The prevalence of methicillin‐resistant S .aureus and methicillin‐resistant coagulase negative Staphylococcus was 14 .3% (1/7) and 43 .2% (19/44) ,respectively . About 44 .4% (8/18) of the E .coli and K . pneumoniae isolates produced extended spectrum beta‐lactamases .All the gram‐positive cocci were sensitive to vancomycin and linezolid and slightly resistant to chloramphenicol (6 .3% ) , moxifloxacin (8 .5% ) , and rifampicin (9 .5% ) , but highly resistant to cefazolin (90 .0% ) ,followed by ampicillin (76 .7% ) ,oxacillin (71 .2% ) and penicillin (69 .7% ) . Coagulase negative Staphylococcus isolates were sensitive to vancomycin , linezolid , tigecycline , quinupristin‐dalfopristin and daptomycin ,but all resistant to cefazolin and ampicillin ,and highly resistant to penicillin (91 .9% ) and oxacillin (82 .5% ) .All the gram‐negative bacilli were sensitive to meropenem ,ertapenem ,cefoperazone‐sulbactam and tigecycline .About 80 .6% and 65 .5% of the gram‐negative bacilli were resistant to ampicillin and peperacillin ,respectively .E .coli isolates were sensitive to meropenem ,ertapenem and piperacillin‐tazobactam but highly resistant to ampicillin (81 .3% ) and piperacillin (71 .4% ) . Conclusions Gram‐positive cocci especially Staphylococcus and gram negative bacteria E .coli are major pathogens in peritoneal dialysis‐related peritonitis .Adequate microbiological culture and suitable antimicrobial therapy are key to successful treatment of the peritonitis associated with peritoneal dialysis .
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Objective To evaluate clinical application value of polymerase chain reaction (PCR) detection for bacteria in peritoneal dialysis associated peritonitis (PDAP).Methods Peritoneal dialysis fluid specimens were collected from January 2014 to December 2014 in The First Affiliated Hospital of Anhui Medical University.Conventional bacterial culture and PCR detection were used respectively.According to the bacterial 16S rRNA gene, universal primers were devised and designed, based on reference, the specific primers of 17 kinds of experimental bacteria.Real-time fluorescent PCR (Real-time PCR, qPCR) amplification was implemented.The establishment of standard strain DNA extract was used as positive control;sterile double distilled water was used as negative control.Results (1) The traditional bacterial culture results showed that positive proportion was 26/40 in specimen of 40 cases, gram-positive strains accounting for 18/26.Main species were epidermis staphylococcus (5/26), hemolysis staphylococcus (4/26), escherichia coli (4/26), and streptococcus viridans (3/26).(2) The PCR detection results showed that total positive rate was 33/40 in 40 patients specimens, among which 2 cases of positive samples ended up with no specific strains being detected;the main bacteria strains in PCR were not different from ordinary culture results.(3) With bacterial culture as the gold standard, the detection sensitivity of PCR technology for PDAP pathogenic bacteria was 96.15％ and specificity was 42.86％;the detection positive rate was significantly higher than ordinary culture method.(4) PCR technology for detecting pathogenic bacteria could produce results within 4-6 hours, while reported positive results in the traditional bacterial culture would take (77.88±15.53) hours, which was significantly longer than PCR.Conclusion Compared with traditional bacteria culture method, PCR method is more sensitive, simple, and quick.Bacteria detection using PCR technique is of clinic applied value in PDRP.
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Objective To investigate the renoprotective effect of transforming growth factor beta activator kinase 1 (TAK1) inhibitor 5Z-7-oxozeaenol (OZ) in diabetic db/db mice and the mechanism.Methods Twenty-four male db/db mice were randomly divided into two groups:db/db mice (db/db,n=12) and db/db mice with 5Z-7-oxozeaenol treatment (db/db+OZ,n=12).Another group of wild type mice (n=12) was held as the control group.OZ 2 mg/kg was administrated by intraperitoneal injection every other day.At week 8 and 12 after 5Z-7-oxozeaenol treatment,blood glucose (BG),body weight (BW),kidney weight (KW) and urinary albumin excretion rate (UAER) were evaluated.Kidney pathological lesions were detected by light and electron microscopy.NF-κB p65,monocyte chemotactic protein-1 (MCP-1) and tumor necrosis factor-ot (TNF-o) were detected by immunohistochemistry.Western blotting was used to detect p-TAK1,TAB1,p-p38MAPK and IL-1β expression,while ICAM-1 and MCP-1 mRNA levels were evaluated by real-time PCR.Results Compared with control group,the levels of BG,BW,KW and UAER were higher (P ＜ 0.01) in db/db mice group,while BW,KW and UAER levels were significantly decreased in db/db + OZ group compared with that in db/db mice group (P ＜ 0.05).In week 8 and 12 db/db mice,glomerular volume and extracellular matrix were increased,while pathological lesions in kidney tissue were positively improved by TAK1 inhibitor.Immunohistochemistry showed that NF-κB p65,MCP-1 and TNF-α expression levels were apparently increased in db/db mice group compared with that in control group (P ＜ 0.05) and were significantly inhibited by TAK1 inhibitor (P ＜ 0.05).Western blotting showed that p-TAK1,TAB1,p-p38MAPK and IL-1β expression levels were higher in db/db mice group than that in control group (P ＜ 0.05) and lower in db/db+ OZ group than that in db/db mice group (P ＜ 0.05).Moreover,real-time PCR showed that the expressions of ICAM-1 and MCP-1 mRNA were higher in db/db mice group than that in control group and lower in db/db+OZ group than that in db/db mice group (P ＜0.05).Conclusions TAK1 Inhibitor can down-regulate MAPK and NF-κB pathway to restrain the reaction of inflammation and alleviate kidney injury in diabetic db/db mice.
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Purpose To investigate the clinical characteristics and Oxford classification of IgA nephropathy patients with hyperurice-mia. Methods 151 IgA nephropathy patients confirmed by renal biopsy in 2013 were analyzed retrospectively. The patients were di-vided into the two groups:IgA nephropathy patients with or without hyperuricemia. Morphological changes were evaluated with Oxford classification scoring system and Lee’s grades. A comparative analysis of clinical manifestations and pathological injuries was performed between the two groups. Results Incidence of hyperuricemia in IgA nephropathy patients was 48. 3% and was more common in young men. Hypertension was associated with hyperuricemia. Oxford classification of IgA nephropathy patients with hyperuricemia was pre-dominant M1E0S1T0 and Lee’s grades presented with grade Ⅲ. The outstanding histopathologic features with higher plasma uric acid levels indicated higher tubulointerstitial chronicity, higher glomerular sclerosis ratio, accompanied by a decline in glomerular filtration rate. There was no significant difference of vascular lesions. Conclusions The prevalence of hyperuricemia in IgA nephropathy pa-tients is high. Oxford classification shows IgA nephropathy with hyperuricemia are associated with more severe tubulointerstitial lesions and lower GFR.
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Objective To evaluate the effectiveness of thoracic electrical bioimpedance(TEB)in monitoring the cardiac function of peritoneal dialysis patients.Methods One hundred and one patients with continuous ambulatory peritoneal dialysis (CAPD) and 30 healthy persons (control group)were included in the study.Thoracic electrical bioimpedance (TEB) noninvasive hcmodynamic monitoring and echocardiography were taken to analyze the correlation between indexes.Results Echocardiography showed that left atrial diameter (LAD),left ventricular end diastolic diameter (LVDd),left ventricular end systolic diameter (LVDs),interventricular septal thickness （IVST),interventricular septal thickness (PAP),left ventricle weight index (LVMI) of CAPD group were higher than that of the control group (all P ＜ 0.05),early and late wave of mitral valve flow (E/A) of CAPD group was lower than that of control group (P ＜ 0.05).TEB monitoring showed that cardiac output (CO),stroke volume (SV),acceleration index (ACI),ejection fraction (EF),velocity index (Ⅵ) of CAPD group were significantly lower than that of control group (all P ＜ 0.01),systolic time ratio (STR),SVR,TFC of CAPD group were significantly higher than that of control group (P ＜ 0.01).Correlation analysis show that left ventricular ejection fraction (LVEF) was negatively correlated with BNP (r =-0.467,P ＜ 0.01),LVMI was positively correlated with BNP (r=0.416,P ＜ 0.01),PEP,STR and TFC were positively correlated with BNP (r =0.404,P ＜ 0.01; r =0.572,P ＜ 0.01; r=0.471,P ＜ 0.01),EF was negatively correlated with BNP (r =-0.664,P ＜ 0.01).Correlation analysis between echocardiogaphy and TEB monitoring index showed there was significant correlation between EF and LVEF (r =0.451,P ＜ 0.01),SVR and TFC were positively correlated with LVMI (r =0.232,P ＜ 0.05; r =0.284,P ＜ 0.05),SV was positively correlated with E/A (r =0.285,P ＜ 0.05),pre-ejection period (PEP) and STR were negatively correlated with LVEF (r =-0.389,P ＜ 0.01; r =-0.446,P ＜ 0.01),TFC was positively correlated with LAD (r=0.279,P ＜ 0.05).Conclusion TEB monitoring can accurately evaluate the cardiac function with the advantage of dynamic monitoring and simple operation.It can partly replace the echocardiography test.
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ObjectiveTo investigate the effect of tacrolimus (FK506) on macrophage accumulation,proliferation and activation in the kidney of early diabetic rats and to explore its possible mechanism of renal protection.Methods Rats were randomly divided into control,model and tacrolimus groups.Diabetic model rats were induced with intraperitoneal injection of streptozotocin.Tacrolimus(0.5 or 1.0 mg·kg-1 ·d-1) was orally administered once a day for 4 weeks.Kidney weight index(KWI),24-h urinary albumin excretion rate(UAER) and creatinine clearance rate(Ccr) were measured.Kidney pathology was observed by light microscopy.ED-1,PCNAandiNOSpositivemacrophagesweredetectedbysingleanddoublestainingof immunohistochemistry.Results KWI increased in model group and was significantly reduced by tacrolimus treatment with 1.0 mg·kg-1 ·d-1 (P＜0.05).UAER elevated in model group and was markedly attenuated by tacrolimus treatment with 0.5 and 1.0 mg·kg-1 ·d-1 (P＜0.05).Elevated glomerular volume of model rats was significantly decreased by tacrolimus treatment with 0.5 and 1.0 mg·kg-1·d-1 (P＜0.05),and increased indices of tubulointerstitial injury were only ameliorated by 1.0 mg·kg-1·d-1 tacrolimus(P＜0.01).Marked accumulation of ED-1+ cells in diabetic kidney was found,which was not inhibited by tacrolimus treatment with 0.5 and 1.0 mg·kg-1·d-1.ED-1PCNA+ cells and ED-1+ iNOS+ cells were significantly elevated in kidneys of model group,while they were significantly inhibited by tacrohmus treatment with 0.5 and 1.0 mg·kg-1·d-1 (P＜0.01).Conclusion Tacrolimus can ameliorate early renal injury of diabetic rats and its mechanism may be partly associated with the suppression of increased macrophages activation.
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AIM To study effects of ACE inhibitor on the ex pression of GluT4 mRNA and protein in diabetic rat heart. METHODS The following groups of rats were randomly designed: control rats, diabetic ra ts and diabetic rats treated with benazepril (an ACE inhibitor). After 4 weeks o f treatment, ACE activities were determined by fluorimetric assay in plasma and heart; Myocardial GluT4 mRNA expression were measured by Northern blot analysis; GluT4 protein expression were measured by Western blot analysis. RESULT S After 4 weeks of treatment, there was a significant increase in myocard ial ACE activities despite a trend toward reduce in plasma activitics, ACE activ ities were inhibited by 92 1%, 89 0% in plasma and heart, respectively; Northe rn blot analysis revealed that the expression of GluT4 mRNA was reduced in diabe tic rat heart by 40%, and treatment with benazepril did not prevent the diabetes -induced reduction of GluT4 mRNA; However, Western blot analysis revealed that benazepril did prevent the diabetes-induced reduction of GluT4 protein in cell membrane of diabetic rat heart. CONCLUSION Benazepril could significantly suppress ACE activities in diabetic rat heart, bu t it did not influence the expression of the myocardial GluT4 mRNA. However, it did prevent the diabetes-induced reduction of GluT4 protein in cell membrane of rat heart.
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Uninephrectomy was performed in a ll rats of this study, and diabetic model was induced in partial rats by streptozo tocin. Then these rats were divided into uninephrectomy group, diabetes group an d benazepril-treated diabetes group. After 4 weeks, renal tubulo-interstitial morphological change was observed and type Ⅳ collagen, fibronectin and transfor ming growth factor ? 1 (TGF-? 1) proteins as well as TGF-? 1 mRNA were d etermined. The results suggested that benazepril played a protective role in ren al tubulo-interstitial injury, which was associated partially with down-regula ted overexpression of TGF-? 1.
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Objective To evaluate the efficiency of low molecular weight heparin(LMWH, fraxiparine) given as a single predialysis bolus injection with reused dialyzers in comparison with standard heparin(SH) administered with a continuous infusion. Methods 30 hemodialysis patients were studied in a radomized crossover fashion. Dialyzers fibrer bundle volumes(FBV), predialysis hemocrit and 2 h clearance of urea, creatinine were observed in the first, the fourth dialysis. The plasma heparin activities(anti-Fxa levels) were measured by the chromogenic substrate assay in 0 h, 2 h, 4 h of dialysis. Results Significant increase (P0.05); in addition, the plasma heparin activity(anti-Fxa levels) were comparable in both groups after 2 h of dialysis, however, they were significantly higher after 4 h in the LMWH than those in the SH group (P<0.05). Conclusion LMWH as a single bolus dose can prevent decrease in dialyzer clearance. It is clinically worthy of further popularity.