Screening chondrocyte necroptosis-related genes in the diagnosis and treatment of osteoarthritis.

Background: Osteoarthritis (OA) is the most common form of joint diseases, with hallmark of cartilage degeneration. Recent studies have shown that the pathogenesis of OA is associated with chondrocyte necroptosis. Methods: In this study, we used single-cell RNA sequencing (scRNA-seq) and bulk RNA sequencing data to analyze necroptosis regulation in OA chondrocytes. We performed enrichment analysis, carried out experimental validation, constructed machine learning models, and docked drug molecules. Results: After least absolute shrinkage and selection operator (LASSO) algorithm screening, 4 hub genes (RIPK3, CYBB, HSP90AB1, and TRAF5) with diagnostic characteristics were obtained. Following the comparison of multiple models, the Bayesian model with an average area under curve (AUC) value of 0.944 was finally selected. We found that nimesulide exhibited strong binding affinity to CYBB and HSP90AB1, and experimentally verified that nimesulide reduced the expression of RIPK3 and CYBB, suggesting its potential as an inhibitor of chondrocyte necroptosis. Furthermore, scRNA-seq results showed that necroptosis in OA was significantly upregulated on regulatory chondrocytes (RegC) compared to other chondrocyte subtypes. Conclusions: The results indicate that nimesulide might be used to treat OA by inhibiting chondrocyte necroptosis through down-regulation of RIK3 and CYBB genes. This study reveals the role of chondrocyte necroptosis in OA, and suggests a potential therapeutic strategy by regulating necroptosis with nimesulide.

Single-cell aggrephagy-related patterns facilitate tumor microenvironment intercellular communication, influencing osteosarcoma progression and prognosis.

Osteosarcoma, a common malignant tumor in children, has emerged as a major threat to the life and health of pediatric patients. Presently, there are certain limitations in the diagnosis and treatment methods for this disease, resulting in inferior therapeutic outcomes. Therefore, it is of great importance to study its pathogenesis and explore innovative approaches to diagnosis and treatment. In this study, a non-negative matrix decomposition method was employed to conduct a comprehensive investigation and analysis of aggregated autophagy-related genes within 331,394 single-cell samples of osteosarcoma. Through this study, we have elucidated the intricate communication patterns among various cells within the tumor microenvironment. Based on the classification of aggregated autophagy-related genes, we are not only able to more accurately predict patients' prognosis but also offer robust guidance for treatment strategies. The findings of this study hold promise for breakthroughs in the diagnosis and treatment of osteosarcoma, intervention of aggrephagy is expected to improve the survival rate and quality of life of osteosarcoma patients.

Sustained intra-articular reactive oxygen species scavenging and alleviation of osteoarthritis by biocompatible amino-modified tantalum nanoparticles.

Recent studies highlight the vital role of oxidative stress and reactive oxygen species (ROS) during progression of osteoarthritis (OA). Attenuating oxidative stress and reducing reactive oxygen species generation in joints represent reasonable strategies for the treatment of osteoarthritis. To address the potential question for clinical translation, and improve the biocompatibility and long-term performance of current antioxidants, the present study provided high biocompatible small positively charged tantalum nanoparticles (Ta-NH2 NPs) with sustained intra-articular catalase activity and first applied to osteoarthritis intervention. Our in vitro results showed that Ta-NH2 NPs were stable with good biocompatibility, and protected viability and hyaline-like phenotype in H2O2-challenged chondrocytes. In addition, the in vivo biodistribution data demonstrated a sustained retention of Ta-NH2 NPs in the joint cavity, particularly in articular cartilage without organ toxicity and abnormality in hemogram or blood biochemistry indexes. Finally, compared with catalase (CAT), Ta-NH2 NPs exhibited long-term therapeutic effect in monosodium iodoacetate (MIA) induced osteoarthritis model. This study preliminarily explored the potential of simply modified metal nanoparticles as effective reactive oxygen species scavenging agent for osteoarthritis intervention, and offered a novel strategy to achieve sustained reactive oxygen species suppression using biocompatible Ta-based nano-medicine in oxidative stress related diseases.

Premature ventricular contractions with acute successful radiofrequency catheter ablation near the atrioventricular node using reversed C curve technique.

BACKGROUND: We sought to clarify the electrophysiological (EP) characteristics of premature ventricular contractions (PVCs) with acute successful radiofrequency catheter ablation (RFCA) near the atrioventricular node (AVN). METHODS AND RESULTS: Eighteen patients with acute successful RFCA near the AVN were included in this study. Systematic mapping was performed with two mapping methods: antegrade mapping technique (group A) and reversed C curve mapping technique (group R). RFCA was preferentially performed underneath the tricuspid valve (TV) with reversed C curve technique in all patients. The a amplitude/v amplitude ratio during sinus rhythm in group A was significantly larger than in group B (0.19 ± 0.10 vs 0.06 ± 0.02, p < 0.01). The earliest bipolar activation preceded the QRS onset in group A was significantly smaller than in group R (19.6 ± 4.9 vs 24.4 ± 6.6 ms (ms), p < 0.01). Pace mapping in group A and group R demonstrated perfect QRS morphology (12/12) match only in 5.6% (one patient) and 16.7% (3 patients) of patients, respectively. The mean duration of successful RFCA was 8.2 ± 2.4 s in 13 patients (72.2%). Early (within 3 days) and late (one-year) recurrence rates were 5.6% (one patient) and 16.7% (3 patients), respectively. No atrioventricular block occurred during RFCA or the one-year follow up. CONCLUSIONS: PVCs near the AVN are a subgroup of idiopathic PVCs with distinctive EP features. RFCA using reversed C curve technique is effective and safe for the acute elimination of these challenging AVN-PVCs.

SIMULATION AND MEASUREMENT OF EXTERNAL ELECTROMAGNETIC ENVIRONMENT OF TOKAMAK DEVICE.

Magnetic confinement nuclear fusion is an important way to realize controllable nuclear fusion. Due to the large current and complicated coil arrangement, there is a complicated electromagnetic environment around the fusion device. In this paper, the B-dot sensor is used to measure the magnetic field, the D-dot sensor is used to measure the electric field, the MAXWELL electromagnetic simulation software is used to simulate the electromagnetic field strength; the simulation and measurement of the spherical Tokamak SUNIST device and the measurement of MARX generator are carried out, then we give corresponding electromagnetic protection suggestions.

NUMERICAL ANALYSIS OF SAFETY ZONE OF A LARGE FLAT-PLATE BOUNDED-WAVE EMP SIMULATOR.

The safety zone of a large flat-plate bounded-wave electromagnetic pulse simulator was analyzed using the 3D electromagnetic simulation software Computer Simulation Technology. First, the double-limit requirement cited from the GB 8702 for an instantaneous pulse was clarified compared with the International Commission on Non-Ionizing Radiation Protection guidelines. This means that both the amplitude of the time-domain waveforms and all frequency components should be satisfied with the respective exposure limits. Then, the leakage field of a large flat-plate bounded-wave simulator was simulated. After analyzing the peak amplitude of an instantaneous electric field in a certain area, the observation points along six directions were specified, and the corresponding amplitudes were given. Furthermore, it was verified that the time-domain electric field of the critical points was satisfied with the frequency-domain exposure limits. Finally, the safety distances lower than the reference levels were given, and the safety zones corresponding to the three common exposure limits were obtained.

Surface-assisted assembly of a histidine-rich lipidated peptide for simultaneous exfoliation of graphite and functionalization of graphene nanosheets.

Biological molecules have promising potential to exfoliate graphite and produce biocompatible graphene nano-materials for biomedical applications. Here, a systematic design of a histidine-rich lipidated peptide sequence is presented that simultaneously exfoliates graphite flakes and functionalizes the resulting graphene nanosheets (∼150 nm lateral size) with long-term dispersion stability in aqueous solution (>8 months). The details of peptide/peptide and peptide/graphite interactions are probed using various microscopy, spectroscopy and molecular dynamics simulation methods. The results show that histidine and stearic acid interact with the graphite surface through π-π stacking and hydrophobic forces, respectively. Surface-assisted assembly of peptide molecules is then initiated via hydrogen bonds between deprotonated histidine segments, and a textured peptide nano-structure is formed. The work of adhesion between the peptide and graphite is found to be high enough to promote exfoliation of graphite flakes through layer-by-layer peeling of graphene nanosheets. The positively charged arginine in the peptide is exposed outward, and is responsible for the stable dispersion. The peptide molecules are sufficiently small, presenting the possibility to insert into and increase the spacing between the graphitic layers for enhanced exfoliation. The peptide-functionalized graphene nanosheets not only show great biocompatibility with cells in vitro, but also enhance cancer drug uptake by the cells.

The fractional synthesis rates of plasma proteins as determined using deuterated water are sensitive to dietary intake of lysine in rats.

Traditionally, the effect of dietary lysine upon health is determined through the concentrations of plasma proteins, but sometimes they are not responsive to lysine intake. We hypothesized that the fractional synthesis rates (FSRs) of plasma proteins may be more sensitive to dietary intake of lysine than protein concentrations in plasma. Seventy-two male Sprague-Dawley rats were divided randomly into three groups based on their diets provided for 18 weeks: low lysine (LG), normal lysine (NG) and high lysine (HG). Rats underwent labeling with deuterated water, a more reliable tracer than amino-acid tracers. The FSRs of albumin and immunoglobulin (Ig) G in plasma increased with increasing dietary intake of lysine. However, the albumin concentration in plasma in rats in the LG did not decrease significantly compared with that in the NG, and a similar result was shown for the IgG concentration between the NG and HG. These results suggested that the FSRs of albumin and IgG in plasma were more sensitive to dietary intake of lysine than their concentrations, and could be useful as sensitive indicators of the effect of dietary lysine upon health.

Danshen modulates Nrf2-mediated signaling pathway in cisplatin-induced renal injury.

Danshen, an efficacious agent for cardiovascular diseases, has been found to play an essential role in kidney injury. In the present study, the effect of Danshen on cisplatin-induced renal dysfunction was investigated in a mouse model. Danshen was administered to mice at a dose of 3 g/kg 4 days before and 3 days after cisplatin treatment. A single intraperitoneal injection of 20 mg/kg cisplatin was used to induce nephrotoxicity. The mice were sacrificed 72 h after cisplatin intoxication. Biochemical parameters including serum creatinine and blood urea nitrogen were analyzed. Histopathological changes of kidney tissues were detected using HE staining. Antioxidant enzymes (GSH-Px and SOD) and peroxidative product (MDA) were detected. Protein expressions of Nrf2 and its target genes including HO-1 and NQO1 were measured by Western blotting. The results showed that pretreatment with Danshen significantly reduced serum creatinine and blood urea nitrogen in the cisplatin-treated mice. Histopathological examination showed that Danshen mitigated the renal damage induced by cisplatin. Moreover, Danshen restored the activities of antioxidant enzymes (GSH-Px and SOD) and normalized the MDA contents in renal tissues. Western blotting revealed that Danshen enhanced the expressions of Nrf2 and its target genes in cisplatin-exposed mice. It was suggested that Danshen protects against the cisplatin-induced renal impairment in the mice, which is potentially associated with the upregulation of Nrf2-mediated signaling pathway.

Danshen Modulates Nrf2-mediated Signaling Pathway in Cisplatin-induced Renal Injury / 华中科技大学学报（医学）（英德文版）

Danshen,an efficacious agent for cardiovascular diseases,has been found to play an essential role in kidney injury.In the present study,the effect of Danshen on cisplatin-induced renal dysfunction was investigated in a mouse model.Danshen was administered to mice at a dose of 3 g/kg 4 days before and 3 days after cisplatin treatment.A single intraperitoneal injection of 20 mg/kg cisplatin was used to induce nephrotoxicity.The mice were sacrificed 72 h after cisplatin intoxication.Biochemical parameters including serum creatinine and blood urea nitrogen were analyzed.Histopathological changes of kidney tissues were detected using HE staining.Antioxidant enzymes (GSH-Px and SOD) and peroxidative product (MDA) were detected.Protein expressions of Nrf2 and its target genes including HO-1 and NQO1 were measured by Western blotting.The results showed that pretreatment with Danshen significantly reduced serum creatinine and blood urea nitrogen in the cisplatin-treated mice.Histopathological examination showed that Danshen mitigated the renal damage induced by cisplatin.Moreover,Danshen restored the activities of antioxidant enzymes (GSH-Px and SOD) and normalized the MDA contents in renal tissues.Western blotting revealed that Danshen enhanced the expressions of Nrf2 and its target genes in cisplatin-exposed mice.It was suggested that Danshen protects against the cisplatin-induced renal impairment in the mice,which is potentially associated with the upregulation of Nrf2-mediated signaling pathway.

The influence of mutant lactobacilli on serum creatinine and urea nitrogen concentrations and renal pathology in 5/6 nephrectomized rats.

OBJECTIVES: To explore the capacity of mutant lactobacilli to remove creatinine (Cr) and urea nitrogen (UN) via the gastrointestinal tract and its effects on renal pathology in the 5/6 nephrectomized rat model of chronic renal failure. METHODS: Sixty Sprague-Dawley rats were randomly divided into a Sham group, a Model group, a wide-type Lactobacilli group (L.B group), and a Mutant Lactobacilli group (Mut-L.B group). The rats in the Model, LB and Mut-L.B groups underwent 5/6 nephrectomy. Eight weeks after administration, 24-h urine, orbital blood and digestive secretions were collected to analyze Cr and UN levels. Pathological changes in nephridial tissues were observed by hematoxylin and eosin and Masson trichrome staining, and the expression of TGF-ß1 and FN was detected by immunohistochemistry. RESULTS: There were no significant differences in urinary Cr and UN levels among the Sham, L.B and Mut-L.B groups (p > .05), while serum and digestive Cr and UN levels were significantly decreased in the Mut-L.B group (p < .01). Furthermore, renal tubular injury and interstitial fibrosis were significantly reduced and TGF-ß1 and FN expression was decreased (p < .05) in the Mut-L.B group. CONCLUSION: Mutant lactobacilli decreased serum Cr and UN levels, reduced the expression of TGF-ß1 and FN in renal tissues and alleviated renal interstitial injury and fibrosis in a rat model of chronic renal failure in a mechanism that may involve decomposition and not just excretion of small molecule toxins in the gastrointestinal tract.

Lactobacillus bulgaricus mutants decompose uremic toxins.

BACKGROUND/AIMS: We aim to obtain a probiotic strain from Lactobacillus bulgaricus by testing its capability to decompose uremic toxins to provide new intestinal bacteria for the treatment of chronic renal failure. METHODS: Original L. bulgaricus was cultured with the serum of uremic patients and then mutated by physical (ultraviolet) and chemical (diethyl sulfate) methods repeatedly. Using creatinine decomposition rate as an observed index, we selected the best strains which decreased the most concentration of the creatinine. We then tested its ability to decompose urea, uric acid, serum phosphate, parathyroid hormone, and homocysteine and its genetic stability. RESULTS: After inductive and mutagenic treatment, DUC3-17 was selected. Its decomposition rate of creatinine, urea nitrogen, uric acid, phosphorus, parathyroid hormone, and homocysteine were 17.23%, 36.02%, 9.84%, 15.73%, 78.26%, and 12.69%, respectively. The degrading capacity was sustained over five generations. CONCLUSIONS: After directional induction and compound mutation, L. bulgaricus has greater capacity to decompose uremic toxins, with a stable inheritance.

Cloning and expression of a urate oxidase and creatinine hydrolase fusion gene in Escherichia coli.

OBJECTIVE: To construct a plasmid containing a urate oxidase and creatinine hydrolase fusion gene and transform the plasmid into Escherichia coli to decompose uric acid and creatinine. METHODS: According to the GenBank data for the urate oxidase gene, specific primers were designed to amplify and remove the stop codon for the urate oxidase gene. The gene was then ligated into the plasmid pMG36e to construct pMG36e-U. Then, using the GenBank database for the creatinine hydrolase gene, primers were designed to amplify the creatinine hydrolase gene. This gene was ligated into pMG36e-U to form pMG36e-U/C. Next, this construct was transformed into E. coli, which was confirmed by screening the recombinant E. coli and sodium dodecylsulfonate-polyacrylamide gel electrophoresis (SDS-PAGE) analysis. The engineered bacteria were cultured with a specific concentration of creatinine and uric acid for 24 h. Then, the concentrations of creatinine and uric acid in the culture fluid were measured. RESULTS: The recombinant gene fragment was approximately 1.68 kb, and it contained the urate oxidase and creatinine hydrolase genes. The transformed E. coli expressed creatinine hydrolase and uric acid oxidase. The creatinine decomposition rate increased by 43.5%, and the uric acid decomposition rate increased by 42.32%. CONCLUSION: The constructed recombinant plasmid containing a fusion gene of creatinine hydrolase and uric acid oxidase was transformed into E. coli, and the enzymatic activities were expressed.

[Investigation of enterotoxin gene in clinical isolates of Staphylococcus aureus].

OBJECTIVE: To detect the enterotoxin genes of Staphylococcus aureus (SA) isolated from clinical specimens and analyze the correlation between enterotoxin genes and drug resistance of SA. METHODS: The mecA gene and enterotoxin genes A-F of clinical SA isolates were identified by polymerase chain reaction (PCR), and the genes were sequenced to investigate the correlation of these genes to drug resistance. RESULTS: The detection rate of enterotoxin genes was 100% in 67 methicillin- resistant SA (MRSA), showing no significant difference from the rate in 57 methicillin-sensitive SA (MSSA) (83.5%, χ(2)=0.203, P>0.05). Of the 116 strains carrying enterotoxin genes (93.5%), the detection rates of SEA, SEB, SEC, SED and SEF were 90.5%, 6.9%, 61.3%, 5.2%, 25.9% and 93.5%, respectively, and none of the strains were positive for SEE gene. In these strains, 78 (67.2%) carried 2 or more enterotoxin genes, and the main genotypes were SEA and SEC (33.6%), SEA and SEF (7.8%), and SEA and SEC and SEF (13.8%). Compared with the strains carrying a single enterotoxin gene, those with multiple enterotoxin genes showed a higher drug resistance rate, among which 75% of the SA strains carrying SEA+SEC+SEF were resistant to SXT, significantly higher than the rates of SA carrying SEA (28.6%) and SEA+SEC (38.7%) (P<0.05). The SA strains carrying SEA+SEC+SEF and SEA+SEF showed significantly higher amikacin resistance rates than SA strain carrying SEA (75.0%, 77.0%, 21.5%, respectively, P<0.05). CONCLUSION: Clinical isolates of SA carrying multiple enterotoxin genes have a higher drug resistance rate than those with a single enterotoxin gene, suggesting the the important role of enterotoxin in multidrug resistance.

Shenfushu granule and atropine attenuate microvasculature loss in rat models with 5/6 nephrectomy.

OBJECTIVE: To investigate the effect of Shenfushu granule (SFSG) and atropine treatment on microvessels of the kidney and intestine after chronic renal failure (CRF) induced by 5/6 nephrectomy. METHODS: Sprague Dawley rats were randomly divided into a sham group, a model group, an SFSG group, and an SFSG + atropine group. SFSG was administered daily 1 week after inducing CRF. Rats were sacrificed at the end of the eighth week. Urinary protein and stool and serum urea nitrogen (UN) and creatinine (Cr) levels were assessed. Hematoxylin and eosin and periodic acid-Schiff staining of the kidney and examination of the vascular endothelial growth factor (VEGF) and microvessel density (MVD) levels in kidney and intestine were performed. RESULTS: The Cr and UN levels were significantly increased in blood and stool of the model group. SFSG significantly improved renal function, and the protective effects were further enhanced with the addition of atropine. Glomerular sclerosis, tubulointerstitial fibrosis, and microvessel loss were observed in CRF rats, and these pathological changes were ameliorated in the two treatment groups (p < 0.05), especially in the SFSG + atropine group. The expression of VEGF and MVD was decreased in the CRF rats compared with the sham group. SFSG treatment increased the expression of these proteins and reversed the degree of microvessel loss, glomerular sclerosis, and tubulointerstitial fibrosis (p < 0.05). Co-treatment with atropine enhanced these effects. CONCLUSIONS: SFSG alleviated renal function, upregulated the expression of VEGF and MVD in the kidney and intestine, and attenuated the degree of microvessel loss, glomerular sclerosis, and tubulointerstitial fibrosis in the early stages of CRF in rats, and addition of atropine enhanced these effects.

Isolation and characterization of polymorphic microsatellite loci in Camellia nitidissima Chi (Theaceae).

PREMISE OF THE STUDY: Microsatellite markers were developed in Camellia nitidissima for further population genetic studies. • METHODS AND RESULTS: Eight microsatellite markers were newly developed from C. nitidissima and 7 were transferred from other Camellia species. Two to 13 alleles per locus were identified for these microsatellites. Observed and expected heterozygosities ranged from 0.040 to 0.909, and 0.184 to 0.916, respectively. Four loci showed a significant deviation from Hardy-Weinberg equilibrium and five locus pairs displayed linkage disequilibrium. • CONCLUSIONS: These microsatellite markers will be useful to assess the genetic variation and genetic structure of C. nitidissima.

[Field planting of Bacillus bifidus and Bacillus acidi lactic on various gastrointestinal sites and their decomposition of low molecule urotoxins in rats with renal failure].

OBJECTIVE: To investigate the field planting of Bacillus bifidus and Bacillus acid lactic on mucosa membrane of gaster, jejunal, ileum, ascending colon, and descending colon in rats with renal failure, and to observe their decomposition of creatinine (Cr), urea nitrogen (UN),and uric acid (UA). METHODS: Forty SD rats were randomly divided into 4 groups. Group A was normal control group,and 10 of them were sham-operated. Thirty of them were operated with 5/6 nephrectomy. Group B was pathological control group. Group C were fed Bacillus bifidus and Group D were fed lactobacillus. After 1 week all rats were sacrificed as samples of blood, digestive juice and gastrointestinal mucosa were taken.Bacteria on the gastrointestinal mucosa were counted. The concentration of UN, Cr,and UA of blood and digestive juice was determined. RESULTS: The number of bacteria on the gastrointestinal mucosa of Group B was less than that of Group A (P<0.05), but that of Group C and D was more than that of Group A and B. The bacteria number on the gastric mucosa was least and that on the descending colon was most. There was significant difference in the bacteria number and concentration of Cr, UN,and UA in various sites of the gastrointestinal tract (P<0.05). The concentrations of Cr, UN, and UA in the digestive juice of various sites and serum in Group C and D were lower than those in Group B (P<0.05). Bacteria planting number in the digestive tract has obvious negative correlation with the concentration of Cr,UN, and UA in the blood and digestive tract. CONCLUSION: Field planting of lactobacillns and Bacillus bifidus, and the concentration of low molecule urotoxin are different in various sites of the gastrointestinal tract. It can decrease the concentration of BUN,Cr,and UA in rats with renal failure by feeding lactobacillus and Bacillus bifidus.

[Effect of potassium iodide on prevention of experimental lead nephropathy and expression of nuclear factor-kappaB and fibronectin].

OBJECTIVE: To investigate the effect of potassium iodide on the expression of nuclear factor-kappaB and fibronectin. METHODS: The experiment was performed with 72 SD rats weighing about 180-220 g. The animals were randomly assigned into nine groups. Group A, B, C (n=8) served as control and were fed with distilled water for 1 month, 2 month, 3 month respectively. Group D, E, F (n=8) served as lead exposed and were fed with water with 0.5% lead acetate for 1 month, 2 month, 3 month respectively. Group G, H, I (n=8) served as potassium iodide and lead exposed and were treated with 0.5% lead acetate simultaneously taking potassium iodide 3 mg/100 g weight by intragastric administration for 1 month, 2 month, 3 month respectively. Animals of different groups were sacrificed at the end of the treatment. Ultrastructure of kidney was observed by electron microscopy; Expression of NF-kappaB and FN protein and mRNA in kidney were measured respectively by immunohistochemistry and RT-PCR. RESULTS: Electron microscopic examination revealed potassium iodide could restrain the denaturalization in epithelial cells and mitochondrial cristae. The expressions of NF-kappaB protein (0.2315 +/- 0.0624, 0.3213 +/- 0.0740, 0.4729 +/- 0.0839) and mRNA (0.4370 +/- 0.0841, 0.5465 +/- 0.0503, 0.6443 +/- 0.0538) in all the lead exposed groups continuously increased compared with correspondent control groups; Group I was decreased obviously compared with group F. The expressions of FN protein (0.4243 +/- 0.0595, 0.4917 +/- 0.0891) and mRNA (0.8650 +/- 0.0880, 0.8714 +/- 0.0980) in group E and F increased compared with group B and C, but the expressions of FN protein in group I significantly decreased compared with group F; The expressions of FN mRNA in Group H and I significantly decreased compared with group E and F. CONCLUSION: The potassium iodide can ameliorate renal ultrastructure and degrade expression of nuclear factor-kappaB and fibronectin induced by lead.

[Effect of benazepril on the VEGF and MVD in the remnant kidney of 5/6 subtotal nephrectomized rats].

OBJECTIVE: To explore the effect of benazepril (one of angiotesin converting enzymes) on the expression of vascular endothelial growth factor (VEGF) and the change of microvessel density (MVD) in the remnant kidney of rats that undergone 5/6 subtotal nephrectomy (STNx). METHODS: The male Sprague-Dawley (SD) rats were performed 5/6 nephrectomy to produce chronic renal failure, and randomly divided into a model group (STNx group), a STNx combined with benazepril group (Benazepril group), and a sham group that served as normal controls. Pathological changes of the remnant kidney were evaluated at the 8th week after gastric gavage. Immunohistochemistry Methods were used to examine the expression of VEGF and MVD in the remnant kidney, and the correlation was determined between VEGF, MVD and glomerulosclerosis index (GSI), tubulointerstitial score (TIS), BUN, and creatinine (Cr). RESULTS: UP, BUN, Cr, GSI, and TIS significantly decreased in the benazepirl group (P<0.05); and the expression of VEGF and MVD significant increased (P<0.05). The expression of VEGF was positively related to MVD (P<0.05), and there was negative correlation between VEGF, MVD and GSI, TIS, BUN, Cr (P<0.05). CONCLUSION: The decrease of the expression of VEGF and MVD in the remnant kidney may be involved in the progressive remnant kidney fibrosis and renal function. Benazepril can significantly relieve the remnant kidney fibrosis and protect the renal function by increasing the expression of VEGF and MVD in the remnant kidney.