Transcriptome sequencing of circular RNA reveals a novel circular RNA-has_circ_0114427 in the regulation of inflammation in acute kidney injury.

Acute kidney injury (AKI) is a common serious syndrome characterized by rapid decrease of glomerular filtration rate and the progressive increase of serum creatinine. Circular RNAs (circRNAs) are regulatory RNAs that recently became popular among various diseases. However, the expression profile and function of circRNAs in AKI remain largely unknown. The main function of circRNAs is acting as competing endogenous RNAs (ceRNAs) by binding with microRNAs (miRNAs), as indicated by recent research. In the present study, we established cisplatin-induced AKI model in mice and isolated renal tubular tissues to extract circRNAs for next-generation sequencing (NGS) and bioinformatics analysis. We analyzed the composition, distribution and Gene Ontology terms of circRNAs in cisplatin-induced AKI and revealed differentially expressed circRNAs related to AKI. By finding homologous genes between mouse and human, we identified circRNA- circ-0114427 in humans. We further investigated its function in AKI cell model. Circ-0114427 expression was significantly up-regulated in different AKI cell models. Knockdown of circ-0114427 indicated that circ-0114427 bound to miR-494 as a miRNA sponge to regulate ATF3 expression and further affected the expression of downstream cytokine IL-6. Circ-0114427 regulates inflammatory progression in AKI's early stage via circ-0114427/miR-494/ATF3 pathway. Our findings reveal the expression profile of circRNAs in cisplatin-induced AKI and provide a novel insight into the regulatory mechanism of circRNAs, which may become a new molecular target resource for early diagnosis and treatment strategies.

Caregiving burden and depression in paid caregivers of hospitalized patients: a pilot study in China.

BACKGROUND: Caregiving burden and depression in family caregivers have been investigated, but little is known about how they affect paid caregivers. The aim of this study was to investigate caregiving burden and depression in paid caregivers of hospitalized patients. METHODS: A cross-sectional survey study was conducted in a tertiary referral hospital (Chengdu, China) that enrolled 108 paid caregivers who worked in the inpatient department. The Caregiver Burden Inventory (CBI) and the Center for Epidemiologic Studies Depression (CES-D) scale were incorporated into a self-developed questionnaire to gather demographic information on the following four aspects: general, work, income, and family. RESULTS: The mean total CBI score was 29.7 ± 12.5. The time-dependence burden had the highest score of 15.3 ± 4.0, which was followed by the physical burden score of 6.5 ± 4.6, developmental burden score of 3.7 ± 4.0, social burden score of 3.2 ± 4.0, and emotional burden score of 2.4 ± 3.1. Multiple linear regression analysis showed that a higher CBI was associated with a longer time as a paid caregiver [ß=7.041, 95% Confidence Interval (CI):1.935 to 12.974, p = 0.009], lower income satisfaction (ß= - 6.573, 95% CI: -11.248 to -3.020, p = 0.001), and higher frequency of meeting with their relatives (ß=7.125, 95% CI: 2.019 to 12.456, p = 0.006). The mean CES-D score was 11.9 ± 8.7, and significant depression was found in 28 (25.9%) paid caregivers according to the CES-D score ≥ 16 cut-off. There was a moderate positive correlation between the CBI and CES-D scores (Pearson's r = 0.452, p < 0.001). CONCLUSIONS: A high caregiving burden was commonly observed in paid caregivers of hospitalized patients in China, as was a high prevalence of depression symptoms. Several associated factors were identified that could be areas for future interventions.

Novel risk score of contrast-induced nephropathy after percutaneous coronary intervention.

AIM: Contrast-induced nephropathy (CIN) post-percutaneous coronary intervention (PCI) is a major cause of acute kidney injury. In this study, we established a comprehensive risk score model to assess risk of CIN after PCI procedure, which could be easily used in a clinical environment. METHODS: A total of 805 PCI patients, divided into analysis cohort (70%) and validation cohort (30%), were enrolled retrospectively in this study. Risk factors for CIN were identified using univariate analysis and multivariate logistic regression in the analysis cohort. Risk score model was developed based on multiple regression coefficients. Sensitivity and specificity of the new risk score system was validated in the validation cohort. Comparisons between the new risk score model and previous reported models were applied. RESULTS: The incidence of post-PCI CIN in the analysis cohort (n = 565) was 12%. Considerably high CIN incidence (50%) was observed in patients with chronic kidney disease (CKD). Age >75, body mass index (BMI) >25, myoglobin level, cardiac function level, hypoalbuminaemia, history of chronic kidney disease (CKD), Intra-aortic balloon pump (IABP) and peripheral vascular disease (PVD) were identified as independent risk factors of post-PCI CIN. A novel risk score model was established using multivariate regression coefficients, which showed highest sensitivity and specificity (0.917, 95%CI 0.877-0.957) compared with previous models. CONCLUSION: A new post-PCI CIN risk score model was developed based on a retrospective study of 805 patients. Application of this model might be helpful to predict CIN in patients undergoing PCI procedure.

Inhibition to DRP1 translocation can mitigate p38 MAPK-signaling pathway activation in GMC induced by hyperglycemia.

Diabetic nephropathy (DN) is a serious complication of diabetes with a poorly defined etiology and limited treatment options. Early intervention is a key to preventing the progression of DN. Dynamin-related protein 1 (DRP1) regulates mitochondrial morphology by promoting its fission and is involved in the pathogenesis of numerous diseases. Furthermore, DRP1 is also closely associated with the development of diabetes, but its functional role in DN remains unknown. This study investigated the effect of DRP1 on early stage of DN. DRP1 expression has increased significantly in glomerular mesangial cell (GMC), which is cultivated in high glucose (HG). Ultra-microstructural changes of nephrons, expression of collagen IV and phosph-p38, ROS production, and mitochondrial function were evaluated and, at the same time, were compared with glomerular mesangial cell (GMC) cultured in normal-glucose (NG), mannitol, and a medium with mitochondrial division inhibitor 1 (Midivi-1). Endogenous DRP1 expression increased in DN. Compared to the control groups ofNG and mannitol, overexpression of DRP1 destroyed pathological changes typical of the GMC, like accumulation of extracellular matrix, and an increase in mitochondria division. In addition, Overexpression of DRP1 promoted the activation of p38, the accumulation of ROS, mitochondrial dysfunction, and the synthesis of collagen IV, and all these changes are suppressed by Midivi-1. This study demonstrates that DRP1 overexpression can accelerate pathological changes in the GMC cultured in HG. Further studies are needed to clarify the underlying mechanism of this destructive function.

Two tachykinin-like peptides from skin secretions of Danio rerio.

Tachykinin perform multiple physiological functions such as smoothing muscle contraction, vasodilation, inflammation, the processing of nerve signal, neuroprotection and neurodegeneration. Two novel tachykinin-like peptides named tachykinin-DR1 and -DR2 were identified from skin secretions of Danio rerio in current work. Their amino acid sequences were determined as SKSQHFHGLM-NH(2) and NKGEIFVGLM-NH(2), respectively. They share a conserved FXGLM-NH(2)C-terminal consensus motif. By cDNA cloning, the precursor encoding both tachykinin-DR1 and -DR2 was screened from the skin cDNA library of D. rerio. Tachykinin-DR1 and -DR2 share the same precursor, which is composed of 108 amino acid (aa) residues. Regarding the biological activity, tachykinin-DRs could induce the contraction of isolated strips of guinea pig ileum just like other tackykinins. To our best knowledge, this is the first report of tachykinin from fish skin.

Protein kinase C-delta is involved in induction of NOX1 gene expression by aldosterone in rat vascular smooth muscle cells.

In this study, we focused on the relationship between aldosterone and NOX1 expression in vascular smooth muscle cells (VSMCs). For the first time, with the use of specific inhibitors of protein kinase C (PKC), we report that PKCdelta mediates upregulation of NOX1 induced by 10 nM aldosterone in cultured VSMCs. Participation of PKC in the mediation of NOX1 regulation was further confirmed by the effect of diacylglycerol, a PKC agonist, on the NOX1 RNA in A7r5 cells with Northern blot analysis. To establish cause and effect, we next silenced the PKCdelta gene partly by RNA interference and found knockdown of PKCdelta gene attenuated aldosterone-induced NOX1 expression, generation of superoxide, as well as protein synthesis in VSMCs. Taken together, these data indicated PKCdelta might mediate aldosterone-dependent NOX1 upregulation in VSMCs. In addition, we showed that the cascade from aldosterone to PKCdelta activation had the participation of the mineralocorticoid receptor.

Bioinformatic analysis reveals that the OAS family may play an important role in lupus nephritis.

BACKGROUND: Lupus nephritis (LN) is a common complication of systemic lupus erythematosus that presents a high risk of end-stage renal disease. However, the molecular mechanisms of LN remain unclear. The lack of understanding hinders the development of specific targeted therapy for this progressive disease. OBJECTIVES: In the present study, we used bioinformatics analysis of gene expression profiles from the Gene Expression Omnibus to identify novel targets and potential biomarkers for LN. MATERIAL AND METHODS: A GSE32591 dataset, which included 31 LN glomerular biopsy tissues and 14 living donors' glomerular tissues, was downloaded for further analysis. Differentially expressed genes in LN were analyzed by the limma package. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed for the differentially expressed genes by using the Disease Ontology Semantic and Enrichment and the clusterProfiler software. The protein-protein interaction (PPI) network was then formed using STRING online tool. RESULTS: 440 genes, including 310 upregulated genes and 130 downregulated genes, were found as differentially expressed genes. GO and KEGG analyses revealed that immune response is significantly enriched in such genes. The PPI network showed that ISG15, MX1, OAS1, OAS2, and OAS3 were the hub genes enriched in LN. Along with literature review, the OAS family genes were revealed to be closely associated with LN progression. CONCLUSIONS: our studies provided new insight into the molecular pathogenesis of LN. The OAS family may play an important role in LN and act as a novel molecular candidate for the further study of LN.

[Effects of Artesunate on MCP-1 and MCP-1 mRNA expression of renal tissue in the rat IgA nephropathy model].

OBJECTIVE: To investigate the effects of Artesunate on expression of MCP-1 and MCP-1 mRNA in renal tissue of the rat experimental IgA nephropathy model. METHODS: 40 rats were divided randomly into 4 groups with 10 rats in normal control group while the other 30 in model control group, low dose Artesunate group and high dose Artesunate group after the establishment of IgA nephropathy model. MCP-1 and MCP-1 mRNA in renal tissue were tested by immunohistochemical and RT-PCR methods. RESULTS: The expression of MCP-1 mRNA in model control group was significantly increased (0.4726+/-0.086 vs 0.1445+/-0.095, P<0.05, compared with normal control group), which was suppressed in low dose Artesunate group (0.2844+/-0.065) and high dose Artesunate group (0.2184+/-0.058) (both P<0.05, compared with model control group). In addition, hemouria, proteinuria and pathological changes in renal tissue were improved in the Artesunate groups. CONCLUSION: Artesunate shows the ability of downregulating the expression of MCP-1 in renal tissue, which may explain one of the mechanisms of Artesunate effectiveness in clinical treatment of IgA nephropathy.

Bioinformatic Analysis Reveals Novel Immune-Associated Hub Genes in Human Membranous Nephropathy.

BACKGROUND: Membranous nephropathy (MN) is one of the most common pathologies of the nephrotic syndrome. MN is closely associated with the autoimmune response but its molecular mechanism remains unclear. Bioinformatic network analysis can be used to identify disease-related hub genes. METHODS: The microarray data set GSE47183 of patients with MN containing 21 MN samples and 13 control samples that were obtained from the Gene Expression Omnibus database. Differentially expressed genes (DEGs) were identified using the limma package. Thereafter, gene ontology (GO) enrichment was performed for DEGs using the clusterProfiler package. The protein-protein interaction (PPI) network was established through the Search Tool for the Retrieval of Interacting Genes database and visualized using Cytoscape. Finally, the hub genes were identified through the maximal clique centrality method. RESULT: A total of 642 DEGs were recognized, consisting of 458 upregulated genes and 184 downregulated genes. GO enrichment analysis indicates that DEGs for MN are mainly related to antigen processing and presentation. For the PPI network, we identified approximately nine hub genes. Considering data from the literature, we ultimately identified PSMB8 as a novel hub gene, which could play a significant role in the occurrence and development of MN. CONCLUSION: This study is the first to identify novel hub genes with transcriptome microarray data in MN using bioinformatics. The newly discovered hypothetical hub genes should be functionally tested to determine if they truly play an etiologic role in MN.

Integrated bioinformatics analysis reveals novel hub genes closely associated with pathological mechanisms of immunoglobulin A nephropathy.

Immunoglobulin A (IgA) nephropathy (IgAN) is the most common glomerular disease. The major pathological changes associated with it affect cell proliferation, fibrosis, apoptosis, inflammation and extracellular matrix (ECM) organization. However, the molecular events underlying IgAN remain to be fully elucidated. In the present study, an integrated bioinformatics analysis was applied to further explore novel potential gene targets for IgAN. The mRNA expression profile datasets GSE93798 and GSE37460 were downloaded from the Gene Expression Omnibus database. After data preprocessing, differentially expressed genes (DEGs) were identified. Gene Ontology (GO) enrichment analysis of DEGs was performed. Protein-protein interaction (PPI) networks of the DEGs were built with the STRING online search tool and visualized by using Cytoscape, and hub genes were identified through the degree of connectivity in the PPI. The hub genes were subjected to Kyoto Encyclopedia of Genes and Genomes pathway analysis, and co-expression analysis was performed. A total of 298 DEGs between IgAN and control groups were identified, and 148 and 150 of these DEGs were upregulated and downregulated, respectively. The DEGs were enriched in distinct GO terms for Biological Process, including cell growth, epithelial cell proliferation, ERK1 and ERK2 cascades, regulation of apoptotic signaling pathway and ECM organization. The top 10 hub genes were then screened from the PPI network by Cytoscape. As novel hub genes, Fos proto-oncogene, AP-1 transcription factor subunit and early growth response 1 were determined to be closely associated with apoptosis and cell proliferation in IgAN. Tumor protein 53, integrin subunit ß2 and fibronectin 1 may also be involved in the occurrence and development of IgAN. Co-expression analysis suggested that these hub genes were closely linked with each other. In conclusion, the present integrated bioinformatics analysis provided novel insight into the molecular events and novel candidate gene targets of IgAN.

Effect of restricted protein diet supplemented with keto analogues in end-stage renal disease: a systematic review and meta-analysis.

AIM: To evaluate the efficacy and safety of the restricted protein diet supplemented with keto analogues when applied in end-stage renal disease (ESRD). METHODS: The Cochrane Library, PubMed, Embase, CBM and CENTRAL databases were searched and reviewed up to January 2017. Clinical trials were analyzed using RevMan 5.3 software. RESULTS: Five randomized controlled trials were selected and included in this study according to our inclusion and exclusion criteria. Changes in serum albumin, PTH, triglyceride, cholesterol, calcium, phosphorus, hemoglobin, Kt/v and CRP before and after treatment were analyzed. Meta-analysis results indicated that, compared with normal protein diet, low-protein diet (LPD) supplemented with keto analogues (sLPD) could improve serum albumin (P < 0.00001), hyperparathyroidism (P < 0.00001) and hyperphosphatemia (P = 0.008). No differences in triglyceride, cholesterol, hemoglobin, Kt/v and CRP were observed between different protein intake groups. CONCLUSION: Restricted protein diet supplemented with keto analogues (sLPD) may improve nutritional status and prevent hyperparathyroidism in ESRD patients. The current data were mainly obtained from short-term, single-center trails with small sample sizes and limited nutritional status indexes, indicating a need for further study.

Genetic association of polymorphisms in AXIN1 gene with clear cell renal cell carcinoma in a Chinese population.

AIM: The purpose of the present study is to investigate the association between the polymorphisms in AXIN1 with susceptibility to clear cell renal cell carcinoma (ccRCC). MATERIALS & METHODS:  A total of 284 ccRCC patients and 439 healthy volunteers were enrolled. Totally three tag single nucleotide polymorphisms in AXIN1 gene were genotyped using PCR & restriction fragment length polymorphism. RESULTS: Significantly increased ccRCC risk was observed to be associated with the CT/CC genotypes of rs1805105 and AA genotype of rs12921862. Patients carrying the rs1805105 CT genotype had a 1.92-fold increased risk to developing clinical stage III and IV cancer. CONCLUSION: Our results suggested the rs1805105 CT/CC genotypes and rs12921862 AA genotype may relate to ccRCC development.

[Inflammatoin, oxidative stress and carbonyl stress in uremic patients].

OBJECTIVE: To evaluate the states of inflammation, oxidative stress and carbonyl stress in uremic patients and analyze their relationships. METHODS: One hundred and twenty-eight cases were divided into 6 groups: non-dialysis uremia group (n=25), peritoneal dialysis group (n=19), hemophan(Hem) membrane dialysis group (n=25), polyamide (PS) membrane dialysis group (n=25), diabetes with normal renal function group (n= 23) and normal control group (n=11). Spectrophotometry and immune turbidimetry were used to measure the serum SOD, VitC, VitE, MDA and total carbonyl compounds (TCC) levels. RESULTS: Compared with non-uremia groups, the uremia groups had lower serum SOD, VitE and VitC levels, but higher CRP, MDA and TCC levels (P < 0.01). The peritoneal dialysis group had higher SOD, VitC, VitE levels in comparison with the Hem group, but did not differ from PS group in those levels (P > 0.05). The MDA and TCC levels in the peritoneal dialysis group were lower than those in the two hemodialysis groups, but there were no significant differences in CRP level between the groups. Compared with Hem group, the PS group had higher VitC, VitE levels, higher TCC clearance, and the same SOD, MDA, CRP and pre-dialysis TCC levels. When the variables were analyzed with TCC, the results of multi-variate regression showed that the standardized coefficients were MDA (0.727, P < 0.01), CRP (0.370, P < 0.01), SOD (0.192, P < 0.05), VitC (-0.153, P < 0.01), VitE (0.054, P = 0.30) respectively. CONCLUSION: Uremic patients are in inflammatory, oxidative-stress and carbonyl-stress states. Inflammation and oxidative stress are probably the important mechanism of carbonyl stress. It is not yet clear whether dialysis methods can influence uremic inflammatory, oxidative-stress or carbonyl-stress state.

Mitofusin 2 attenuates the histone acetylation at collagen IV promoter in diabetic nephropathy.

Extracellular matrix (ECM) increase in diabetic nephropathy (DN) is closely related to mitochondrial dysfunction. The mechanism of protective function of mitofusin 2 (Mfn2) for mitochondria remains largely unknown. In this study, the molecular mechanisms for the effect of Mfn2 on mitochondria and subsequent collagen IV expression in DN were investigated. Ras-binding-deficient mitofusin 2 (Mfn2-Ras(Δ)) were overexpressed in rat glomerular mesangial cells, and then the cells were detected for mitochondrial morphology, cellular reactive oxygen species (ROS), mRNA and protein expression of collagen IV with advanced glycation end-product (AGE) stimulation. Preliminary results reveal that the mitochondrial dysfunction and the increased synthesis of collagen IV after AGE stimulation were reverted by Mfn2-Ras(Δ) overexpression. Bioinformatical computations were performed to search transcriptional factor motifs in the promoter region of collagen IV. Three specific regions for TFAP2A binding were identified, followed by validation with chromatin immunoprecipitation experiments. Knocking down TFAP2A significantly decreased the TF binding in the first two regions and the gene expression of collagen IV. Furthermore, results reveal that Mfn2-Ras(Δ) overexpression significantly mitigated TFAP2A binding and also reverted the histone acetylation at Regions 1 and 2 after AGE stimulation. In streptozotocin-induced diabetic rats, Mfn2-Ras(Δ) overexpression also ameliorated glomerular mesangial lesions with decreased collagen IV expression, accompanied by decreased acetylation and TFAP2A binding at Region 1. In conclusion, this study highlights the pathway by which mitochondria affect the histone acetylation of gene promoter and provides a new potential therapy approach for DN.

The effect of calcineurin inhibitors in the treatment of IgA nephropathy: A systematic review and meta-analysis (PRISMA).

BACKGROUND: Immunoglobin A nephropathy (IgAN), the most prevalent form of primary glomerulonephritis, represents the leading cause of kidney failure among East Asian populations. Immunosuppressive treatment regimen, except for a 6-month trial of corticosteroids, has not been approved by the KDIGO guideline yet. Specific and effective treatment is still lacking. We decided to evaluate the efficacy and safety of the calcineurin inhibitors (CNIs) in the treatment of IgAN. METHODS: Database from the Cochrane library, PubMed, Embase, CBM, CNKI, and CENTRAL databases were searched and reviewed up to March 2016. Literature was screened by 2 independent reviewers accordingly. Clinical trials were analyzed using Stata 12.0. RESULTS: Five random control trials and 2 nonrandomized concurrent control trials were selected and included in this study according to our inclusion and exclusion criteria. The rates of complete remission in patients with IgAN were significantly increased in the group of CNIs (RR 1.56, P = 0.002). No statistical difference was observed in the rates of partial remission, or response between the CNIs and steroids alone. Additionally, CNIs resulted in a significant reduction in urinary protein (WMD 0.34, P = 0.002) and increase in serum albumin level (WMD 1.89, P = 0.013). No differences were found in the serum creatinine, estimated glomerular filtration rate, and rates of adverse effects including infection, hyperglycemia, and liver dysfunction. CONCLUSION: With present evidence, CNIs may be promising immunosuppressive agents for IgAN in future. However, large, long-term, multicenter trials are required to confirm our findings.

[Effects of RGD tripeptide on the expression of FAK and HA in glomerular mesangial cells].

OBJECTIVE: Observing the effects of Arg-Gly-Asp (RGD) peptides on the proliferation of glomerular mesangial cells (GMCs), and on the expression of focal adheshion kinase (FAK) and hyaluronic acid (HA) in GMCs. METHODS: GMCs of rats were induced with RGD peptide in vitro. The proliferation of GMCs was measured by MTT; the expression of FAK, by immunohistochemistry; and the quantity of HA, by radioimmunoassay. RESULTS: After being incubated with RGD peptides, some of the attached GMCs became round, detached, and floated. As compared with the control, the proliferation (A value) of the induced with RGD peptide GMCs was significantly lower. After the cultured GMCs had been induced with RGD (1 mmol/L) for 24 h, the expression of FAK decreased by 3.10%, and the secretion of HA decreased by 5.64%. After the cultured GMCs had been incubated with RGD (4 mmol/L) for 8 h and 24 h, the expression of FAK decreased by 6.50% and 15.95%, and the secretion of HA decreased by 6.37% and 18.43%, respectively. CONCLUSION: RGD peptides can inhibit the attachment of the cultured GMCs, reduce the proliferation of GMCs and decrease the secretion of the extracellular matrix.

Clinicopathological and outcome analysis of adult lupus nephritis patients in China.

BACKGROUND: The objective of this study was to assess clinicopathological characteristics and outcomes of lupus nephritis adult patients in China. METHODS: Clinicopathological features, treatment strategies, responses and outcome of 681 adult patients with biopsy-proved lupus nephritis were retrospectively analyzed. RESULTS: Six hundred and eighty-one LN patients were included and followed up for 52.5 ± 14.1 months. Differences in age, disease duration, BP, proteinuria, serum albumin, creatinine, ANCA-positive ratio and SLEDAI scores were noticed between male and female patients, indicating severer disease in male patients. LN IV patients were much severer in systemic damage as well as immunological changes. During follow-up, 354 patients achieved CR, 107 patients achieved PR, 95 patients progressed to ESRD and 36 patients died. Prognosis and treatment response of patients with different histological types differ apparently. Renal outcome of patients with LN II and III was benign, while LN IV, V and VI was poor. Cyclophosphamide was effective in most patients. MMF and CNI could be used as salvage treatment. In multivariate analysis, BP, sCr, hypocomplementemia, severe proliferative lesion (LN IV or VI) and SLEDAI score were recognized as independent indicators of poor renal outcome. Infections, especially pulmonary fungus infection, thrombotic microangiopathy are the most common causes of death in LN patients. CONCLUSIONS: Clinicopathological characteristics, treatment responses and long-term outcomes differ remarkably in LN patients with different gender and pathological subtypes. New indicators of poor renal outcome were identified. Infections and TTP were the most common causes of death in LN patients.

[Effects of cilazapril on the expression of vascular endothelial growth factor and intercellular adhesion molecule-1 in diabetic rat glomeruli].

OBJECTIVE: To assess the effect of cilazapril, an angiotensin-converting enzyme inhibitor (ACEI), on the protection against diabetic nephropathy and on the expression of vascular endothelial growth factor (VEGF) and intercellular adhesion molecule-1 (ICAM-1) in diabetic rat glomeruli. METHODS: The rat model of diabetes mellitus (DM) was produced by injection of streptozocin (STZ). After the treatment with cilazapril [1 mg/(kg.d)] for 2 weeks and 8 weeks, glomerular hypertrophy, renal function and 24 h urinary protein count were measured, and the expression of VEGF and ICAM-1 were investigated by immunohistochemical technique and Mias-2000 pathology computer image analyzer in diabetic rat glomeruli. RESULTS: At 2 weeks, kidney weight/body weight (KW/BW), creatinin clearance rate (CCr) and 24 hours urine protein count increased significantly in DM model group, compared with control (P < 0.05, P < 0.01). Meanwhile, by immunohistochemistry, increased levels of glomerular VEGF and ICAM-1 were shown and their peaks were seen at 8 weeks (P < 0.01). Cilazapril could reduce KW/BW, CCr and 24 hours urine protein count and significantly suppress the overexpression of VEGF and ICAM-1 in cilazapril treatment group after 8 weeks, compared with the DM model group(P < 0.05). CONCLUSION: Cilazapril can suppress the overproduction of two cytokines, VEGF and ICAM-1, thus preventing the progression of diabetic nephropathy.

[Protective effect of angiotensin II receptor blockage on rats with experimental diabetes nephropathy in early stage].

OBJECTIVE: To investigate the possible mechanism of angiotensin II receptor blockage (Losartan) for the decreasing of proteinuria and the protection of renal function in diabetic rats. METHODS: Sixty Wistar rats were divided into 3 groups: Losartan treatment group, diabetes mellitus (DM) model group, and control group. All were treated accordingly for 4 weeks. 24 hours urine protein count, creatinin clearance rate (Ccr), mean arterial pressure (MAP), kidney weight/body weight, ET-1 in blood and urine, IV collagen and fibronectin (FN) in kidney tissue were determined at 1, 2, 4 weeks. RESULTS: In DM model group, the 24 hours urine protein count and MAP, compared with control, increased significantly (P < 0.05) and reached peak at 2 weeks; the decrease of Ccr and the increase of kidney weight/body weight were observed; meanwhile, by immunohistochemistry, increased expression levels of FN, IV collagen were shown in kidney tissues, especially on basement membrane, and significant increase of ET-1 level in blood and urine was also noted. In Losartan treatment group, all of MPA, 24 hours urine protein count, kidney weight/body weight and Ccr decreased, compared with those of model group; ET-1 in blood and urine decreased too, especially the decreasing of ET-1 in urine (P < 0.01). And the expression level of FN and IV collagen was just as small as that in control group. CONCLUSION: Losartan may play a role in inhibiting the synthesis and secretion of ET-1 in kidney and thus it will contribute to the decreasing of proteinuria and the protection of renal function.