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【Objective】 To understand the structural characteristics of lapsed apheresis donors in our blood center and provide guidance for further improving recruitment and retention strategies by retrospectively analyzing the characteristics of lapsed apheresis donors in our center in recent years. 【Methods】 The apheresis donation and lapsed apheresis donors in Zhejiang Blood Center from 2016 to 2020 were statistically analyzed, and the general information of lapsed donors, including gender, blood type, age, education level and occupation composition, were compared and analyzed. The lapse of novel and long-term donors with different frequency were retrospectively analyzed. The SPSS 19.0 statistical software package was used for data analysis. 【Results】 In 2020, the total lapse of apheresis donors decreased by 16.6% as compared with 2016(P<0.05). The lapse rate of donors with blood groups A, B, O and AB was 1∶1∶1∶1, higher in female donors(59.0%) than males(50.0%), and dominated by age group of 18-35(66.3%). With the increase of age, the lapse rate decreased. Donors lapsed were mainly with college or above educational background(60.8%), with high proportion in students and the staff. In 2020, the lapse of novel apheresis donors decreased by 34.1% as compared with 2016, but the average lapse rate of novel apheresis donors was still as high as 70.5%. The average lapse rate of blood donors with different frequency was 52.5%, and the lapse rate decreased significantly with the increase of apheresis donation frequency. The average lapse rate of novel blood donors with whole blood donation experience was lower than those without (56.1% vs 82.9%). 【Conclusion】 Multiple measures for recruitment and retention have effectively reduced the lapse of apheresis donors. However, apheresis donors who are 18-35 years old, with college degree or above, students and staff were the main groups from lapsing. In addition, low-frequency and novel apheresis donors without whole blood donation experience were more likely to be lapsing. Targeted and personalized blood donation services should be further provided, and the management of " full cycle of blood donation" should be strengthened to reduce the lapsing, so as to retain more blood donors.
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This study analyzed the current status of the cultivation process of professional postgraduates of clinical medicine, combining with the case of the auxiliary teaching model of Academic Salons on the WeChat platform in Xiangya Hospital of Central South University. We collected students' satisfaction evaluation of this auxiliary teaching model by questionnaire survey. Through analyzing the results and feedback, we found that the overall satisfaction of this auxiliary teaching model is 71.43%, and the model has a remarkable effect in broadening knowledge, inspiring thinking of clinical diagnosis and treatment, improving ability of scientific research, increasing learning interest, enhancing the ability to link theory with practice, and using the knowledge flexibly. However, there are still some shortcomings in early publicity, understanding students' interests and needs, and improving students' autonomous learning ability. Therefore, using the WeChat platform to carry out academic salons is a good auxiliary teaching model for cultivating the scientific research ability of professional postgraduates of clinical medicine.
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Objective:To investigate the effect of fluorofenidone on renal interstitial fibrosis in rats with unilateral ureteral obstruction (UUO) and to observe the effect of fluorofenidone on the expressions of collagen type Ⅰ (Col Ⅰ),collagen type Ⅲ (Col Ⅲ),α-smooth muscle actin (α-SMA),connective tissue growth factor (CTGF),platelet derived growth factor (PDGF) in the renal tissues of UUO rats.Methods:Male Sprague-Dawley (SD) rats were randomly divided into a sham-operated group,a UUO group,and a flurofenidone group (n=5).UUO model was induced by ligating the left ureter in rats.The rats were treated with 125 mg/(kg.d) fluorofenidone by gastric gavage in the fluorofenidone group at 24 h before the operation,and the rats were treated with the identical dose of 0.5％ sodium carboxyl methyl cellulose (CMC-Na) in the other 2 groups.The rats were sacrificed at 14 days after UUO.Pathological changes of the renal tissue were observed by HE and Masson staining,the mRNA expressions of Col Ⅰ,Col Ⅲ,α-SMA,PDGF and CTGF were detected by real-time PCR,and the protein expressions of Col Ⅰ,Col Ⅲ,PDGF and CTGF were detected by immunohistochemical staining.Results:The renal interstitial damage index,relative collagen area and mRNA and protein expressions of Col Ⅰ and Col Ⅲ in the renal tissues of the rats in the UUO group significantly increased (P＜0.05),and fluorofenidone could reduce these indexes (P＜0.05).Compared with the sham-operated group,the protein expressions ofα-SMA,PDGF,CTGF and the mRNA expressions of PDGF and CTGF in the renal tissues of the rats in the UUO group were increased,but fluorofenidone could decrease the protein expressions of α-SMA,PDGF,CTGF and the mRNA expressions of PDGF and CTGF (P＜0.05).Conclusion:Fluorofenidone (125 mg/kg·d) could attenuate renal interstitial fibrosis through inhibition offibroblast proliferation,myofibroblastic activation,PDGF and CTGF expression.
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Objective To investigate effects of pirfenidone (PFD) on diabetic nephropathy model in db/db mice and to explore its possible mechanisms.Methods (1) Wild-type mice were as the normal control group,and db/db mice were divided into model group and PFD group,with 6 mice in each group.In the PFD group mice were administered continuously by 250 mg· kg-1· d-1 PFD for 18 weeks,and mice in the other two groups were administered by 0.5％ sodium carboxymethyl cellulose.Blood glucose and 24 h urinary albumin were measured.The pathological changes of renal tissue were evaluated by PAS staining,PASM staining,Masson staining and Sirius red staining.The expression of collagen type Ⅳ in kidney tissues was detected by immunohistochemistry.(2) Mouse mesangial cells (SV40 MES-13 cells) were cultured as research objects.They were divided into control group,hyperosmolar group,high glucose (HG) group,and 50,100,200,400,800,1600 mg/L PFD+HG group.BrdU cell proliferation test was used to evaluate cell proliferation rate.Cells were divided into control group,hyperosmolar group,HG group and PFD+HG group.The mRNA expressions of α-smooth muscle actin (α-SMA),collagen type Ⅰ,collagen type Ⅳ,transforming growth factor-β1 (TGF-β1),interleukin (IL)-1β,IL-6 and monocyte chemotactic protein-1 (MCP-1) were detected by real-time PCR.Results (1) Compared with normal control group,the model mice had higher weight,blood glucose and 24 h urinary albumin,accompanied with glomerular hypertrophy,mesangial area expansion,tubulointerstitial fibrosis and deposition of collagen type Ⅳ (all P ＜ 0.05).Compared with those in model group,in PFD group 24 h urinary albumin decreased,glomerular hypertrophy,mesangial area expansion and tubulointerstitial fibrosis alleviated,and the protein expression of collagen type Ⅳ inhibited (all P＜0.05).(2) Compared with those in HG group,MES-13 cell proliferation rates of 100,200,400,800,1600 mg/L PFD+HG groups decreased (all P ＜ 0.05),and the mRNA expressions of α-SMA,collagen type Ⅰ,collagen type Ⅳ,TGF-β1,IL-1β,IL-6 and MCP-1 reduced in 400 mg/L PFD+HG group (all P ＜ 0.05).Conclusions PFD can inhibit high glucose-induced proliferation and activation of glomerular mesangial cells,decrease the expression of TGF-β1 and proinflammatory factors,as well as reduce the synthesis of collagen,which improve renal fibrosis of db/db mice.
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Objective To investigate the effects of fluorofenidone(AKF-PD)on diabetic kidney disease in db/db mice and its possible mechanisms.Methods(1)Fifty-six mice aged 8 weeks(half male and half female),including 42 db/db mice and 14 wild-type mice were studied.Fortytwo db/db mice randomly were divided into model group(mock-treated diabetic db/db mice),AKF-PD(250 mg· kg-1· d-1)treatment group and losartan(20 mg· kg-1· d-1)treatment group.Wild-type mice and model mice were treated with vehicle(0.5％sodium carboxymethylcellulose),while the treatment groups received either AKF-PD or losartan.After 18 weeks,the blood glucose and urinary albumin were measured,the pathological changes of kidney were observed by PAS staining.The protein expressions of type Ⅳ collagen and fibronectin(FN)in kidney tissue were detected by immunohistochemistry.(2)Mouse glomerular mesangial cells(MES-13 cells)were divided into six groups:normal glucose group(5.5 mmol/L glucose),hypertonic group(5.5 mmol/L glucose+19.5 mmol/L mannitol),high glucose group(25.0 mmol/L glucose),AKF-PD group(25.0 mmol/L glucose+400 mg/L AKF-PD)and losartan group(25.0 mmol/L glucose+2 μmol/L losartan).After 72 h treatment,the expressions of type Ⅰ collagen,type Ⅳ collagen and transforming growth factor-β1(TGF-β1)mRNA were detected by realtime PCR,and the content of TGF-β1 protein in the culture supernatant was detected by ELISA.Results(1)Compared with the wild type mice,model mice had increased weight,blood glucose and glomerulosclerosis index(all P ＜ 0.01),accompanied with heavy albuminuria,glomerular hypertrophy,mesangial area expansion and deposition of collagen type Ⅳ and FN(all P ＜ 0.01).Compared with model mice,in AKF-PD and losartan groups 24 h urinary albumin and glomerulosclerosis index decreased(all P ＜ 0.01),glomerular hypertrophy and mesangial area expansion alleviated,and the protein expressions of collagen type Ⅳ and FN were inhibited(all P ＜ 0.01).(2)Compared with the normal glucose group,the mRNA expressions of type Ⅰ collagen and type Ⅳ collagen increased in high glucose group,meanwhile the mRNA and protein expressions of TGF-β1 increased(all P ＜ 0.01).In AKF-PD and losartan groups the expressions of type Ⅰ collagen,type Ⅳ collagen and TGF-β1 were inhibited as compared with high glucose group(all P ＜ 0.05).Conclusion Fluorofenidone may play an anti-fibrotic effect in db/db mice by reducing the expression of TGF-β1 and inhibiting collagen synthesis in glomerular mesangial cells.
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Objective To evaluate immune protective effects of Treponema pallidum(Tp)pcD/Tp92 DNA vaccine delivered through different inoculation routes against Tp-induced skin infection in New Zealand rabbits. Methods A total of 108 New Zealand rabbits were randomly and equally divided into 6 groups:A1 and A2 groups treated with intramuscular injection of empty plasmids pcD and pcD/Tp92 DNA vaccine respectively for 2 sessions, B1, B2, C1 and C2 groups firstly treated with intramuscular injection of the pcD/Tp92 DNA vaccine for 1 session for primary immunization, then receiving nasogastric feeding with pcD/Tp92 DNA vaccine, pcD/Tp92 DNA vaccine+cytosine-phosphate-guanine(CpG)oligodeoxynucleotide (ODN), and recombinant Tp92 protein, and recombinant Tp92 protein+CpG ODN respectively for booster immunization. Enzyme-linked immunosorbent assay(ELISA)was conducted to detect the serum level of anti-Tp92 IgG antibody at week 0, 2, 4, 6, 8 after immunization, the SIgA level in the nasopharyngeal region and vaginal mucosa at week 8 after immunization, as well as levels of interleukin-2(IL-2)and interferon-γ (IFN-γ)in the culture supernatant of rabbit spleen cells at week 8 after immunization, and methyl thiazolyl tetrazolium(MTT)assay was performed to estimate proliferative activity of rabbit splenic lymphocytes in three rabbits from each group. At week 10 after immunization, other 15 rabbits from each group were subcutaneously inoculated with Tp standard strain, and changes of skin lesions at the inoculation site during early-stage infection were observed and recorded. Results At week 8 after immunization, the C2 group showed significantly higher serum level of anti-Tp92 IgG antibody(1.825 ± 0.175), supernatant levels of IL-2 (154.7 ± 14.6)and IFN-γ(277.4 ± 24.4), and proliferative activity of T cells(3.57 ± 0.24)compared with the A2(1.372 ± 0.322, 112.3 ± 13.4, 232.8 ± 25.3, 3.08 ± 0.22, respectively, all P<0.05), B1(0.893 ± 0.297, 76.6 ± 21.5, 165.7 ± 22.6, 2.12 ± 0.14, respectively, all P<0.05)and B2(1.294 ± 0.124, 97.3 ± 18.7, 211.3 ± 24.6, 2.88 ± 0.18, respectively, all P<0.05)groups. In addition, effective immunoprotection was achieved in the C2 group with more production of mucosa-specific SIgA antibody, as well as the lowest Tp-positive rate (6.67%) and ulcer formation rate (6.67%) in skin lesions at the inoculation sites. Conclusion The effective vaccination strategy, namely intramuscular injection of the pcD/Tp92 DNA vaccine for primary immunization followed by nasogastric feeding with mucosal adjuvant CpG ODN combined with recombinant Tp92 protein for booster immunization, can induce the strongest mucosal immune responses and immune protective effects.
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Fibrosis can occur in different organs with high incidence rate and great danger. It still lacks effective drugs for prevention of fibrosis. Fluorofenidone is a newly developed drug with anti-fibrotic activity, which provides a new hope for treating the progressive fibrotic diseases. Recent studies have shown that fluorofenidone is a multifunctional small molecule with anti-inflammatory, antioxidative and anti-apoptotic eff ects. It can inhibit the activation and proliferation of myofibroblasts, promote the degradation of extracellular matrix and regulate the cellular signal transmission. Fluorofenidone can be applied to attenuate the progression of renal, hepatic and pulmonary fibrosis.
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Humans , Apoptosis , Extracellular Matrix , Fibrosis , Kidney , Pathology , Liver Cirrhosis , Pulmonary Fibrosis , Pyridones , Pharmacology , Signal TransductionABSTRACT
OBJECTIVE@#To establish the evaluation index system for equalization of basic public health services and to test its value in practice.@*METHODS@#We developed the index system through expert scored evaluation and then chose a city in Hunan for the research object. The sources of data and the methods of collection for each indicator were identified. The reliability and validity of index system was tested. The methods of AHP (analytic hierarchy process) and TOPSIS (technique for order preference by similarity to an ideal solution) were applied to comprehensively evaluate the public health services among nine counties in the city.@*RESULTS@#The Cronbach's alpha coefficient, which described reliability test result on evaluation index system for equalization of basic public health services, was 0.750. The cumulative contribution rate reached 89.32% after validity test with extraction of 5 common factors through factor-analysis. The sorting results from AHP or TOPSIS method are very close except two districts.@*CONCLUSION@#Evaluation index system for equalization of basic public health services established in this study is in good validity and reliability, which can be objectively applied to analyze the current status of basic public health services.
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China , Health Services , Reference Standards , Health Services Research , Public Health , Reproducibility of Results , Surveys and QuestionnairesABSTRACT
OBJECTIVE@#To determine the effect of curcumin on diabetic nephropathy in db/db mice and its possible mechanism.@*METHODS@#Ten female db/db mice were randomly divided into 2 groups: one was treated with curcumin at 200 mg/(kg.d) and the other was a placebo group. Five age-matched db/m mice were grouped as the controls. In the curcumin group, curcumin was administered to db/db mice for 18 weeks. At the end of the experiment, the blood glucose and albumin were measured, and the kidney tissue sections were stained with PAS to observe the pathological changes. The expression of collagen IV and FN in the kidney was detected by immunohitochemistry staining. Western blot was used to detect the phosphorylation of signal transducer and activator of transcription 3 (STAT3) and IκB in the kidney.@*RESULTS@#Compared with db/m mice, the weight and blood glucose of db/db mice were markedly increased, accompanied with heavy proteinuria, glomerulus hypertrophy, mesangial area expansion, thickening of basement membrane and ECM deposition. The phosphorylation of STAT3 was upregulated and the degradation of IκB was increased. Compared with the db/db mice, curcumin significantly decreased the urinary albumin, inhibited the phosphorylation of STAT3 and the degradation of IκB, and reduced the expression of collagen IV and FN in the kidney.@*CONCLUSION@#Curcumin can obviously decrease albuminuria and attenuate glomerular sclerosis in diabetic db/db mice by inhibiting phosphorylation of STAT3 and degradation of IκB.
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Animals , Female , Mice , Albuminuria , Blood Glucose , Collagen Type IV , Metabolism , Curcumin , Pharmacology , Diabetes Mellitus, Type 2 , Diabetic Nephropathies , Drug Therapy , Fibronectins , Metabolism , I-kappa B Proteins , Metabolism , Kidney , Metabolism , Phosphorylation , Proteinuria , STAT3 Transcription Factor , MetabolismABSTRACT
OBJECTIVE@#To develop a scientific and effective evaluation index system for equalization of basic public health services.@*METHODS@#Through 2 rounds of expert evaluation, based on the relative importance of expert scoring on each index, index was screened according to the scores of mean and coefficient of variation and the weight were determined.@*RESULTS@#The two rounds of consulting experts response rates were more than 90%, and the average authority coefficients were 0.779 and 0.781. The coordination coefficients were 0.229 and 0.349. The evaluation index system of basic public health services was composed of 3 first level, 17 second level and 47 third level indicators after 2 rounds of consultation.@*CONCLUSION@#The evaluation index system of basic public health services is reasonable, and it can be used to evaluate the equalization of basic public health services.
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Health Services , Reference Standards , Health Services Research , Public Health , Reference StandardsABSTRACT
Objective:To determine the characteristics and differences in bleomycin-induced lung ifbrosis model by repeated low-dose intravenous injection and single dose intratracheal instillation of bleomycin. Methods:Forty male ICR (Institute for Cancer Research) mice were randomly divided into a model group I, a model group II, and 2 control groups (10 mice in each group). In model group I, bleomycin was injected intravenously at 10 mg/(kg·d) for 14 consecutive days;and in model group II, bleomycin was instilled intratracheally at 5 mg/kg. The 2 control groups were given isotonic saline solution. At the 28th day, the mice were sacrificed and the bronchoalveolar lavage lfuid (BALF) was collected. The total cells and proteins in the BALF, pulmonary coeffcient, and hydroxyproline (HYP) content were determined. The pathological changes were observed by the eosin staining and Masson's trichrome staining. Results:1) Both intravenous injection and intratracheal instillation of bleomycin resulted in severe and extensive inlfammation and ifbrosis in the lungs. The total cells and proteins in the BALF, HYP content, pulmonary coeffcient and the pathological score of pulmonary ifbrosis were all signiifcantly increased in the 2 model groups (P0.05). Conclusion:The pulmonary fibrosis model can be successfully established by intravenous injection or intratracheal instillation of bleomycin, but the sites of pulmonary ifbrosis are different. The histological changes caused by the repeated low-dose intravenous injection of bleomycin is more similar to idiopathic pulmonary ifbrosis than that by the single dose intratracheal instillation.
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Objective:To establish a method to determine the metabolites in rat kidney tissues by gas chromatography-mass spectrometry (GC-MS) combined with chemometric techniques. Methods:Metabolites were separated and identiifed on HP-5MS column (30 m × 0.25 μm × 0.25 mm). The initial column temperature was 100℃lasting 3 min, and then programmed at 8℃/min to 300℃, maintaining at this temperature for 6 min. hTe internal standard was heptadecanoic acid. hTe grinded kidney tissue was exacted by methanol. hTe supernatant was dried by nitrogen. Atfer the oximation and derivation, the supernatant was analyzed by GC-MS. hTe overlapped peaks were resolved into pure chromatogram and mass spectra with chemometric techniques. Qualitative analysis was performed by comparing the obtained pure mass spectra with those in NIST mass spectra database and certiifcated by the standards and the references. hTe internal method was used for semi-quantitation. Results:A total of 53 compounds were identiifed. hTe main constitutions in the kidney tissue were amino acids, saccharides, fatty acids and urea. Conclusion:hTe combination of methods is rapid and accurate for the analysis of metabolites in the kidney tissue, which provides more information for further study of metabonomics in kidney tissues.
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Objective To investigate the expression of p21 and p53 in renal interstitial fibrosis rats and the effect of enalapril on it. Methods Sprague-Dawley rats were randomly divided into 3 groups, shame operation rats group, unilateral urethral obstruction and enalapril treatment group. Histological chan-ges were observed by Masson stain. The expression of p21 mRNA and p53 mRNA was detected by RT-PCR. Results With degree of interstitial fibrosis aggravating, the expression of p21 and p53 increasing,p21 and p53 expression of UUO rats at every time point were positive correlative. Enalapril can inhibit the expression of p21 and p53. Concinsion p21 and p53 expression increased in UUO rats renal cortex and enalapril can significantly inhibit its expression, p21 may participate in the pathogenesis of renal tubule-in-terstitial fibrosis through p53 pathway.
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OBJECTIVE@#To explore the mechanism of enalapril for renal interstitial fibrosis by observing the effect of enalapril on the expression of transforming growth factor-beta1(TGF-beta1), p-Smad2/3 and Smad7 in renal tissuess of unilateral urethral obstruction (UUO) rat model.@*METHODS@#Thirty female Sprague-Dawley(SD) rats were randomly subdivided into a sham-operated group, a model group and an enalapril treated group. UUO model was induced by ligating the left ureter of rats. All rats were sacrificed 14 days after UUO. Pathological changes of the renal tissue were observed by HE and Masson staining, the protein expressions of Collagen I (ColI), TGF-beta1, p-Smad2/3 and Smad7 were detected by immunohistochemical staining,and the mRNA expressions of TGF-beta1 and Smad7 were detected by RT-PCR.@*RESULTS@#The renal interstitial damage index, the relative Collagen area and the expression of ColI in the model group significantly increased(P<0.01). Enalapril reduced these indexes. The protein and mRNA expressions of TGF-beta1 and the protein expressions of p-Smad2/3 were low in the sham-operated group, but were strongly positive in the model group, and enalapril could decrease the expressions of TGF-beta1 and p-Smad2/3(P<0.01). The protein and mRNA expressions of Smad7 in the model group were less than that in the sham-operated group(P<0.01),and enalapril could improve the expressions of Smad7(P<0.01).@*CONCLUSION@#Enalapril could inhibit the renal interstitial fibrosis by affecting TGF-beta1, p-Smad2/3 and Smad7 of TGF-beta/smads pathway in the renal tissues of UUO rats.
Subject(s)
Animals , Female , Rats , Angiotensin-Converting Enzyme Inhibitors , Pharmacology , Enalapril , Pharmacology , Fibrosis , Kidney , Metabolism , Pathology , RNA, Messenger , Genetics , Metabolism , Random Allocation , Rats, Sprague-Dawley , Smad2 Protein , Genetics , Metabolism , Smad3 Protein , Genetics , Metabolism , Smad7 Protein , Genetics , Metabolism , Transforming Growth Factor beta1 , Genetics , Metabolism , Urethral ObstructionABSTRACT
OBJECTIVE@#To dynamically observe the effect of enalapril on the expression of transforming growth factor beta1 (TGF-beta1), connective tissue growth factor (CTGF), alpha-smooth muscle actin (alpha-SMA), and Smad7 in the obstructed kidney after unilateral ureteral obstruction (UUO) in rats, and to investigate the effect of enalapril on transdifferentiation of renal tubular epithelial cells.@*METHODS@#The model rats were induced by ligating the left ureter. Male Sprague-Dawley (SD) rats were divided into a normal control (sham-surgery) group, a model group, and a treatment group (enalapril 10 mg/ (kg * d) by gastric gavage from 24 h before the obstruction day). Rats were sacrificed on day 3, 7, 14, 21 after UUO was initiated. Sections of the renal tissue were stained with hematoxylin and eosin stain, which were used for histological and morphometric studies of the pathological change of the obstructed kidney. Real-time PCR was performed to examine the expression of TGF-beta1 mRNA and CTGF mRNA, and Western blot was performed to examine the expression of Smad7, alpha-SMA, and CTGF in the obstructed kidney.@*RESULTS@#The score of renal interstitial lesion increased with the extension of obstruction. The expression of TGF-beta1 mRNA, CTGF mRNA, alpha-SMA and CTGF increased in the model group with the extension of obstruction; but Smad7 expression decreased. Compared with the UUO group,the degree of renal interstitial lesion and the expression of TGF-beta1 mRNA, CTGF mRNA, alpha-SMA and CTGF were decreased, but the expression of Smad7 increased in the treatment group. Enalapril could significantly decrease TGF-beta1 mRNA on day 3, 7, 14, 21 after UUO. Enalapril could significantly affect the expression of CTGF mRNA,alpha-SMA,CTGF and Smad7 on day 3, 7, 14 after UUO initiation.@*CONCLUSION@#Enalapril significantly alleviates renal interstitial fibrosis by suppressing the expression of TGF-beta1, CTGF and alpha-SMA, upregulating the expression of Smad7, and has better effect at early stage (within 14 days after the UUO).
Subject(s)
Animals , Male , Rats , Actins , Genetics , Metabolism , Angiotensin-Converting Enzyme Inhibitors , Therapeutic Uses , Connective Tissue Growth Factor , Genetics , Metabolism , Enalapril , Therapeutic Uses , Fibrosis , Kidney Tubules , Pathology , Rats, Sprague-Dawley , Smad7 Protein , Genetics , Metabolism , Transforming Growth Factor beta1 , Genetics , Metabolism , Ureteral Obstruction , Drug Therapy , Metabolism , PathologyABSTRACT
OBJECTIVE@#To determine the expression and effect of hypoxia-inducible factor 1alpha (HIF-1alpha) in chronic kidney fibrosis, and to observe the effect of perindopril on its expression.@*METHODS@#The rat models of chronic kidney fibrosis were induced by 5/6 nephrectomy, and 11 successful 5/6-nephrectomized rats were randomly assigned to 2 groups: a surgery group (n=6) and a treatment group (perindopril, n=5). A control group was induced by sham operation. Five weeks later, Picro-Sirius red stained was applied to measure collagen in the kidney, and Western blot was used to test HIF-1alpha protein; The expression of HIF-1alpha and CTGF mRNA in the kidney was analyzed by real-time PCR.@*RESULTS@#Picro-Sirius red stained revealed significant accumulation of collagens in the surgery group than the control group; and lower accumulation of collagens in the treatment group than the surgery group. Western blot showed higher deposit HIF-1alpha in the surgery group than the control group (P<0.01) and lower deposit HIF-1alpha in the treatment group than the surgery group (P<0.01). Real time PCR showed higher expression of HIF-1alpha and CTGF mRNA in the surgery group than the control group (P<0.01)and lower expression of HIF-1alpha and CTGF mRNA in kidney of the treatment group compared with the surgery group (P<0.01). The expression of CTGF had positive correlation with HIF-1alpha (r=0.68, P<0.01).@*CONCLUSION@#The HIF-1alpha may induce kidney fibrosis through CTGF. Perindopril may decrease the expression of HIF-1alpha and CTGF to ameliorate kidney fibrosis.
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Animals , Male , Rats , Connective Tissue Growth Factor , Genetics , Metabolism , Fibrosis , Metabolism , Hypoxia-Inducible Factor 1, alpha Subunit , Genetics , Metabolism , Kidney , Pathology , Kidney Diseases , Drug Therapy , Metabolism , Nephrectomy , Perindopril , Pharmacology , Therapeutic Uses , RNA, Messenger , Genetics , Metabolism , Random Allocation , Rats, Sprague-DawleyABSTRACT
ObjectiveTo investigate the effects of losartan on angiotensin (Ang)Ⅱ-induced the generation of oxidative stress and expression of transforming growth factor β1(TGF-β1) in rat proximal tubular epithelial cells and to explore its underlying mechanism. MethodsNRK-52E cells, a rat proximal tubular epithelial cell line, were applied to explore the antioxidationand antifibrosis of losartan. The expression of three subunits of nicotinamide-adenine dinucleotide phosphate (NADPH) oxidase, including p47phox, Nox-4, p22phox, and TGF-β1 were determined by real-time RT-PCR and/or Western blot. The generation of reactive oxygen species (ROS) was measured by DCF fluorescence analysis. Superoxide dismutase (SOD) in the supernatant was measured by colorimetric method. Results10-7 mol/L Ang Ⅱ up-regulated p22prox, p47phox and Nox-4 mRNA and protein expression, and the mRNA increased by 5.57-fold, 5.55-fold and 9.41-fold at 24 h (P<0.01, respectively) and the protein increased by 4.53-fold, 4.17-fold and 6.50-fold at 24 h (P<0.01, respectively) as compared with control. Losartan greatly reduced the mRNA elevation of p22prox, p47phox and Nox-4 by 2.71-fold, 2.18-fold and 5.23-fold (P<0.01, respectively) and reduced the protein elevation by 3.20-fold, 2.30-fold and 4.30-fold (P<0.01, respectively) as compared with control. Losartan also inhibited ROS generation induced by Ang Ⅱ in rat proximal tubular epithelial cells. SOD level in the supernatant was markedly decreased after Ang Ⅱ stimulation, while losartan could increase SOD levels (P<0.01). Furthermore, losartan signficantly inhibited Ang Ⅱ-induced TGF-β1 mRNA up-regulation by 64% (P<0.01). ConclusionsLosartan acts as an anti-oxidative and anti-fibrotic agent via the mechanisms of blocking NADPH oxidase-dependent oxidative stress and inhibiting TGF-β1 expression.
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Objective To determine the association between asymmetric dimethylarginine (ADMA), an endogenous inhibitor of nitric oxide (NO) synthase, with atherosclerosis in patients with chronic kidney disease (CKD). Methods One hundred thirty-eight CKD patients were enrolled in this study. Serum levels of L-arginine, ADMA, and SDMA were measured by high-performance liquid chromatography (HPLC). Common carotid arteries intimae-medial thickness (CCA-IMT) ,cross-sectional calculated intimae-medial thickness(cIM area)and atherosclerotic plaque were detected by noninvasive high-resolution B-mode ultrasonography. Results Serum levels of ADMA and SDMA were significantly increased in CKD patients (n=138) compared with age matched healthy subjects (n=42,P＜0.01). ADMA and SDMA levels increased with the progression of renal dysfunction and were negatively related to creatinine clearance (Ccr) in pre-dialysis patients (r=-0.315,P＜0.05;r=-0.426,P＜0.01). Serum levels of ADMA and SDMA in dialysis patients (n=74)were significantly higher than those in pre-dialysis patients (P＜0.05). Patients with carotid artery plaques showed significantly higher levels of ADMA compared with those without plaques. Serum levels of ADMA closely correlated with the mean IMT (r=0.471, P＜0.01) and cIM area value (r=0.430, P＜0.01). These correlations remained significant even after adjusting GFR,age,gender ,and other risk factors for atherosclerosis in the multiple regression analysis. Conclusion Serum levels of ADMA increased with the progression of CKD and may play a role in the pathogenesis of accelerated atherosclerosis in CKD patients.
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Objective The aim of this paper was to investigate the changes in cyclic 3'5'-guanosine monophosphate (cGMP) before and after hemodialysis to estimate the value of cGMP to the dry boby-weight. Methods: Plasma cGMP levels (by radioimmunoassay), cardiothoracic ratio (CTR), and the body weight (BW) before and after hemodialysis were determined in chronic hemodialysis patients and clinical signs and symptoms were observed at the same time. Results ① The predialytic cGMP value of the patients was significantly higher than that of healthy controls (P<0.05). ② The postdialytic cGMP level was significantly lower than the predialytic cGMP level (P<0.01). ③ Postdialytic CTR and BW values were significantly lower than predialytic values (P<0.01). ④Compared to those of predialysis, postdialytic clinic signs and symptoms of the patients were significantly relieved. Conclusions ① The plasma cGMP level can sensitively reflect the hydration state and is a reliable marker for dry body-weight estimation.②The measurement of plasma cGMP combined with clinical parameters and radiological indexes permit a more accurate dry body-weight estimation.
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Objective To indentify the effect of hemodialysis(HD) and continuous veno-venous hemofiltration (CVVH) on serum hepatocyte growth factor (HGF) in the patients with acute renal failure (ARF). Methods Of 28 patients with ARF, 19 received HD and 9 underwent CVVH. HGF concentrations in patients serum and ultrafiltrate were measured by ELISA. Results Compared with the controls, serum HGF concentration increased significantly in ARF patients (P