Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 3.809
Filtrar
1.
Chem Biol Interact ; 335: 109332, 2021 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-33387473

RESUMO

Renal fibrosis is a major cause of renal failure in diabetic nephropathy. Tropisetron is an antagonist of the 5HT3 receptor that exhibits anti-fibrosis effects. The present research aimed to investigate the protected role of tropisetron against renal fibrosis of diabetic nephropathy and its molecular mechanisms. For this purpose, male Wistar rats were allocated into 5 groups of control, tropisetron, diabetes, tropisetron + diabetes, and glibenclamide + diabetes (n = 7). After induction of type 1 diabetes with a single injection of STZ, tropisetron (3 mg/kg) and glibenclamide (1 mg/kg) were given to the rats daily by intraperitoneal injection for 2 weeks. The obtained data revealed that the treatment of diabetic rats with tropisetron led to a significant decrease in the elevated blood glucose, serum cystatin c, and urinary total protein (UTP) level, indicating the improvement of the impaired kidney function. Moreover, the results of Masson's trichrome staining showed that fibrosis attenuated in the kidney of diabetic rats after tropisetron treatment. RT-PCR and Western blotting revealed that TGF-ß1, the apoptotic mediator, and p53 were considerably declined in the kidney of diabetic rats in response to tropisetron treatment. Meanwhile, the expressions of matrix metalloproteinase-9 (MMP-9) and matrix metalloproteinase-2 (MMP-2) were increased. These notable effects were equipotent with glibenclamide, as a standard drug, suggesting that tropisetron can alleviate renal fibrosis in diabetic nephropathy. Our data indicate that tropisetron could improve kidney function and attenuate renal fibrosis through regulation of TGF-ß1, p53, and expression of extracellular matrix metalloproteinases.


Assuntos
Nefropatias Diabéticas/tratamento farmacológico , Fibrose/tratamento farmacológico , Rim/efeitos dos fármacos , Substâncias Protetoras/uso terapêutico , Tropizetrona/uso terapêutico , Animais , Diabetes Mellitus Experimental/induzido quimicamente , Diabetes Mellitus Experimental/complicações , Diabetes Mellitus Experimental/patologia , Nefropatias Diabéticas/complicações , Nefropatias Diabéticas/patologia , Fibrose/patologia , Fibrose/prevenção & controle , Glucose/metabolismo , Rim/patologia , Masculino , Proteínas/metabolismo , Ratos Wistar , Estreptozocina
2.
Kidney Int ; 99(2): 301-303, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-33509348

RESUMO

Risks of kidney failure and heart failure are markedly reduced by inhibition of the sodium glucose cotransporter 2 (SGLT2) in patients with diabetic kidney disease. In a post hoc analysis of the Study of Diabetic Nephropathy with Atrasentan (SONAR) trial, drop-in SGLT2 inhibitor usage during the atrasentan enrichment period led to greater reduction in albuminuria compared with atrasentan alone. These data support the hypothesis of greater longer-term kidney protection by combination SGLT2 inhibition and endothelin A receptor antagonism that could be tested in future clinical trials.


Assuntos
Diabetes Mellitus Tipo 2 , Nefropatias Diabéticas , Insuficiência Cardíaca , Inibidores do Transportador 2 de Sódio-Glicose , Albuminúria/tratamento farmacológico , Nefropatias Diabéticas/tratamento farmacológico , Nefropatias Diabéticas/etiologia , Antagonistas dos Receptores de Endotelina , Taxa de Filtração Glomerular , Glucose , Humanos , Sódio , Inibidores do Transportador 2 de Sódio-Glicose/efeitos adversos
3.
Medicine (Baltimore) ; 100(1): e23702, 2021 Jan 08.
Artigo em Inglês | MEDLINE | ID: mdl-33429738

RESUMO

BACKGROUND: Diabetic peripheral neuropathy is a common complication of diabetes and the main cause of disability. At present, there is no specific therapeutic regimen. Mecobalamin is often used as a neurotrophic drug, and its long-term effects are not satisfactory when used alone. Clinical practice indicates that traditional Chinese medicine injection with mecobalamin has a therapeutic advantage in treating diabetic peripheral neuropathy while it lacks evidence-based medicine. In this scheme, the efficacy and safety of traditional Chinese medicine injection with mecobalamin in treating diabetic peripheral neuropathy has been studied. METHODS: Computers were used to search the English database (PubMed, the Cochrane Library, Embase, Web of Science), and Chinese database (CNKI, Wanfang, CBMDISC, VIP). Besides, manual searching was conducted to search for Baidu Scholar, CHICTR, Google Scholar. During the establishment of the database to November 2020, a randomized controlled trial on traditional Chinese medicine injection with mecobalamin in treating diabetic peripheral neuropathy was conducted. There were 2 researchers independently conducting data extraction and quality evaluation of literature on the included studies, RevMan5.3 was performed for meta-analysis on the included literature. RESULTS: In this study, the efficacy and safety of traditional Chinese medicine injection with mecobalamin in treating diabetic peripheral neuropathy was evaluated by the total effective rate, motor nerve conduction velocity, sensory nerve conduction velocity, adverse reactions, and glucose metabolism level. CONCLUSION: This study can provide an evidence-based basis on the clinical applications of traditional Chinese medicine injection with mecobalamin in the treatment of diabetic peripheral neuropathy. ETHICS AND DISSEMINATION: The study does not involve patient privacy or rights and does not require approval from an ethics committee. The results may be published in peer-reviewed journals or disseminated at relevant conferences. OSF REGISTRATION NUMBER: DOI 10.17605/OSF.IO/KPW5E.


Assuntos
Protocolos Clínicos , Nefropatias Diabéticas/tratamento farmacológico , Medicina Tradicional Chinesa/normas , Vitamina B 12/análogos & derivados , Humanos , Medicina Tradicional Chinesa/métodos , Metanálise como Assunto , Revisões Sistemáticas como Assunto , Vitamina B 12/farmacologia , Vitamina B 12/normas , Vitamina B 12/uso terapêutico
5.
Artigo em Inglês | MEDLINE | ID: mdl-33461698

RESUMO

Irbesartan, (2-butyl-3-({4-[2-(2H-1,2,3,4-tetrazol-5-yl)phenyl]phenyl}methyl)-1,3-diazaspiro[4.4]non-1-en-4-one), is a member of non-peptide angiotensin II receptor antagonists used worldwide in the treatment of hypertension and diabetic nephropathy in hypertensive patients with type 2 diabetes, elevated serum creatinine, and proteinuria. Irbesartan can be used alone or in combination with other antihypertensive agents (e.g., hydrochlorothiazide). These combination products are indicated for hypertension in patients with uncontrolled hypertension with monotherapy or first line in patients not expected to be well controlled with monotherapy. Irbesartan is also indicated for the treatment of diabetic nephropathy in patients with type 2 diabetes and hypertension, an elevated serum creatinine, and proteinuria. Irbesartan exerts its action mainly via a selective blockade action on AT1 receptors and the consequent reduced pressor effect of angiotensin II. This article discusses, by a critical comprehensive review of the literature on irbesartan in terms of its description, names, formulae, elemental composition, appearance, and therapeutic uses. The article also discusses the methods for preparation of irbesartan, its physical-chemical properties, analytical methods for its determination, pharmacological-toxicological properties, and dosing information.


Assuntos
Antagonistas de Receptores de Angiotensina/farmacologia , Nefropatias Diabéticas/tratamento farmacológico , Hipertensão , Irbesartana/farmacologia , Antagonistas de Receptores de Angiotensina/uso terapêutico , Anti-Hipertensivos/farmacologia , Anti-Hipertensivos/uso terapêutico , Diabetes Mellitus Tipo 2 , Humanos , Hipertensão/tratamento farmacológico , Irbesartana/uso terapêutico
6.
Lancet Diabetes Endocrinol ; 9(1): 22-31, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-33338413

RESUMO

BACKGROUND: Dapagliflozin reduces the risk of kidney failure and heart failure in patients with chronic kidney disease. We aimed to investigate the effects of dapagliflozin on kidney, cardiovascular, and mortality outcomes according to presence or absence of type 2 diabetes and according to underlying cause of chronic kidney disease, reported as diabetic nephropathy, chronic glomerulonephritides, ischaemic or hypertensive chronic kidney disease, or chronic kidney disease of other or unknown cause. METHODS: DAPA-CKD was a multicentre, double-blind, placebo-controlled, randomised trial done at 386 study sites in 21 countries, in which participants with a urinary albumin-to-creatinine ratio of 200-5000 mg/g and an estimated glomerular filtration rate (eGFR) of 25-75 mL/min per 1·73m2 were randomly assigned (1:1) to dapagliflozin 10 mg once daily or matching placebo, as an adjunct to standard care. The primary outcome was a composite of sustained decline in eGFR of at least 50%, end-stage kidney disease, or kidney-related or cardiovascular death. Secondary efficacy outcomes were a kidney-specific composite (the same as the primary outcome but excluding cardiovascular death), a composite of cardiovascular death or hospital admission for heart failure, and all-cause mortality. In this study, we conducted a prespecified subgroup analysis of the DAPA-CKD primary and secondary endpoints by presence or absence of type 2 diabetes and by aetiology of chronic kidney disease. DAPA-CKD is registered with ClinicalTrials.gov, NCT03036150. FINDINGS: The study took place between Feb 2, 2017, and June 12, 2020. 4304 participants were randomly assigned (2152 to dapagliflozin and 2152 to placebo) and were followed up for a median of 2·4 years (IQR 2·0-2·7). Overall, 2906 (68%) participants had a diagnosis of type 2 diabetes, of whom 396 (14%) had chronic kidney disease ascribed to causes other than diabetic nephropathy. The relative risk reduction for the primary composite outcome with dapagliflozin was consistent in participants with type 2 diabetes (hazard ratio [HR] 0·64, 95% CI 0·52-0·79) and those without diabetes (0·50, 0·35-0·72; pinteraction=0·24). Similar findings were seen for the secondary outcomes: kidney-specific composite outcome (0·57 [0·45-0·73] vs 0·51 [0·34-0·75]; Pinteraction=0·57), cardiovascular death or hospital admission for heart failure (0·70 [0·53-0·92] vs 0·79 [0·40-1·55]; Pinteraction=0·78), and all-cause mortality (0·74 [0·56-0·98] vs 0·52 [0·29-0·93]; Pinteraction=0·25). The effect of dapagliflozin on the primary outcome was also consistent among patients with diabetic nephropathy (n=2510; HR 0·63, 95% CI 0·51-0·78), glomerulonephritides (n=695; 0·43, 0·26-0·71), ischaemic or hypertensive chronic kidney disease (n=687; 0·75, 0·44-1·26), and chronic kidney disease of other or unknown cause (n=412; 0·58, 0·29-1·19; Pinteraction=0·53), with similar consistency seen across the secondary outcomes. The proportions of participants in the dapagliflozin and placebo groups who had serious adverse events or discontinued study drug due to adverse events did not vary between those with and those without type 2 diabetes. INTERPRETATION: Dapagliflozin reduces the risks of major adverse kidney and cardiovascular events and all-cause mortality in patients with diabetic and non-diabetic chronic kidney disease. FUNDING: AstraZeneca.


Assuntos
Compostos Benzidrílicos/uso terapêutico , Diabetes Mellitus Tipo 2/tratamento farmacológico , Glucosídeos/uso terapêutico , Insuficiência Cardíaca/induzido quimicamente , Falência Renal Crônica/induzido quimicamente , Adulto , Idoso , Compostos Benzidrílicos/efeitos adversos , Doenças Cardiovasculares/induzido quimicamente , Doenças Cardiovasculares/epidemiologia , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/epidemiologia , Nefropatias Diabéticas/tratamento farmacológico , Nefropatias Diabéticas/epidemiologia , Método Duplo-Cego , Feminino , Glucosídeos/efeitos adversos , Insuficiência Cardíaca/epidemiologia , Humanos , Rim/efeitos dos fármacos , Rim/patologia , Rim/fisiopatologia , Falência Renal Crônica/epidemiologia , Masculino , Pessoa de Meia-Idade , Insuficiência Renal Crônica/complicações , Insuficiência Renal Crônica/tratamento farmacológico , Insuficiência Renal Crônica/epidemiologia , Resultado do Tratamento
7.
Diab Vasc Dis Res ; 17(6): 1479164120971220, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33371732

RESUMO

INTRODUCTION: Diabetes mellitus is a progressive disease with cardiovascular complications. We evaluated the impact of a glucagon like peptide-1 (GLP-1) receptor agonist and sodium glucose cotransporter 2 (SGLT-2) inhibitors dapagliflozin and empagliflozin on renal and cardiac function in type 2 diabetes patients with renal impairment. MATERIALS AND METHODS: A total of 156 patients referred with suboptimal glycemic control were assigned to Group G (GLP-1): n = 72 or Group S (SGLT-2 inhibitor)-dapagliflozin (n = 52) or empagliflozin (n = 32). Renal function was assessed every 3 months for 36 months. Cardiovascular parameters were evaluated every 12 months for 36 months. RESULTS: Compared with baseline, HbA1c and systolic blood pressure significantly decreased in both groups (p < 0.05). The estimated glomerular filtration rate decreased, but without significance. Albuminuria decreased significantly in both groups and then subsequently increased after 30 months in Group S. Diastolic cardiac function, assessed by E/e' or left atrial volume index, decreased only in Group G at 36 months. CONCLUSIONS: The GLP-1 receptor agonist and SGLT-2 inhibitors were effective for glycemic and blood pressure control and for maintaining renal function. The GLP-1 receptor agonist improved diastolic function at 36 months.


Assuntos
Albuminúria/tratamento farmacológico , Compostos Benzidrílicos/uso terapêutico , Diabetes Mellitus Tipo 2/tratamento farmacológico , Nefropatias Diabéticas/tratamento farmacológico , Receptor do Peptídeo Semelhante ao Glucagon 1/agonistas , Glucosídeos/uso terapêutico , Incretinas/uso terapêutico , Rim/efeitos dos fármacos , Liraglutida/uso terapêutico , Inibidores do Transportador 2 de Sódio-Glicose/uso terapêutico , Idoso , Albuminúria/diagnóstico , Albuminúria/etiologia , Albuminúria/fisiopatologia , Compostos Benzidrílicos/efeitos adversos , Glicemia/efeitos dos fármacos , Glicemia/metabolismo , Pressão Sanguínea/efeitos dos fármacos , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/diagnóstico , Diabetes Mellitus Tipo 2/fisiopatologia , Nefropatias Diabéticas/diagnóstico , Nefropatias Diabéticas/etiologia , Nefropatias Diabéticas/fisiopatologia , Feminino , Taxa de Filtração Glomerular/efeitos dos fármacos , Glucosídeos/efeitos adversos , Humanos , Incretinas/efeitos adversos , Rim/fisiopatologia , Liraglutida/efeitos adversos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Inibidores do Transportador 2 de Sódio-Glicose/efeitos adversos , Fatores de Tempo , Resultado do Tratamento , Rigidez Vascular/efeitos dos fármacos , Função Ventricular Esquerda/efeitos dos fármacos
8.
Medicine (Baltimore) ; 99(43): e22716, 2020 Oct 23.
Artigo em Inglês | MEDLINE | ID: mdl-33120767

RESUMO

BACKGROUND: Diabetic nephropathy (DN) is the one that of the most common complications of diabetes mellitus (DM). Diabetic patients will experience a high mortality rate when DN progress to end-stage. So, it is extremely important to early treat DN. Although several interventions have been used to treat DN, a conclusive finding has not already been achieved. As one of the most common Chinese medicines, danhong injection (DHI) which has been shown to have various functions has also been prescribed to be as the alternative treatment option. However, no systematic review and meta-analysis has been conducted to objectively and comprehensively investigate its effectiveness and safety. Thus, we designed the current systematic review and meta-analysis to answer whether DHI can be preferably used to timely treat DN. METHODS: We will perform a systematic search to capture any potentially eligible studies in several electronic databases including PubMed, Cochrane library, Embase, China National Knowledgement Infrastructure (CNKI), Wanfang database, and Chinese sci-tech periodical full-text database (VIP) from their inception to August 31, 2020. We will assign 2 independent reviewers to select eligible studies, and assess the quality of included studies with Cochrane risk of bias assessment tool. We will perform all statistical analyses using RevMan 5.3 software. ETHICS AND DISSEMINATION: We will submit our findings to be taken into consideration for publication in a peer-reviewed academic journal. Meanwhile, we will also communicate our findings in important conferences. PROTOCOL REGISTRY: The protocol of this systematic review and meta-analysis has been registered at the International Plateform of Registered Systematic Review and Meta-Analysis Protocols (INPLASY) platform (https://inplasy.com/inplasy-2020-9-0005/, registry number: INPLASY202090005) and this protocol was funded through a protocol registry.


Assuntos
Nefropatias Diabéticas/tratamento farmacológico , Medicamentos de Ervas Chinesas/administração & dosagem , Metanálise como Assunto , Projetos de Pesquisa , Revisões Sistemáticas como Assunto , Intervenção Médica Precoce , Humanos , Injeções
9.
Medicine (Baltimore) ; 99(40): e22377, 2020 Oct 02.
Artigo em Inglês | MEDLINE | ID: mdl-33019413

RESUMO

INTRODUCTION: Diabetic nephropathy (DN) is one of the most common and serious microvascular complications in patients with diabetes, which seriously affects their life quality and survival time. large dose herb Fuling or compound prescription contain large dose Fuling for treatment of DN has already been confirmed. However, due to the lack of evidence, there is no specific method or suggestion, so it is necessary to carry out systematic evaluation on Fuling and provide effective evidence for further research. METHODS AND ANALYSIS: The following databases will be searched from their inception to June 2020: Electronic database includes PubMed, Embase, Cochrane Library, Web of Science, Nature, Science online, Chinese Biomedical Database WangFang, VIP medicine information, and China National Knowledge Infrastructure (CNKI). Primary outcomes:24-hurinary-albumin, Urinary albumin-to-creatinine ratio. Additional outcomes: Serum creatinine, Blood urea nitrogen, Glomerular filtration rate, Endogenous creatinine clearance rate. Data will be extracted by 2 researchers independently, risk of bias of the meta-analysis will be evaluated based on the Cochrane Handbook for Systematic Reviews of Interventions. All data analysis will be conducted by data statistics software Review Manager V.5.3. and Stata V.12.0. RESULTS: The results of this study will systematically evaluate the effectiveness and safety of large dose Fuling intervention for people with DN. CONCLUSION: The systematic review of this study will summarize the current published evidence of large dose Fuling for the treatment of DN, which can further guide the promotion and application of it. ETHICS AND DISSEMINATION: This study is a systematic review, the outcomes are based on the published evidence, so examination and agreement by the ethics committee are not required in this study. We intend to publish the study results in a journal or conference presentations. OPEN SCIENCE FRAMEWORK (OSF) REGISTRATION NUMBER: August 24, 2020. osf.io/ym2c6. (https://osf.io/ym2c6).


Assuntos
Nefropatias Diabéticas/tratamento farmacológico , Wolfiporia , Albuminúria/metabolismo , Creatinina/sangue , Creatinina/urina , Relação Dose-Resposta a Droga , Taxa de Filtração Glomerular , Humanos , Ensaios Clínicos Controlados Aleatórios como Assunto , Projetos de Pesquisa
11.
Am J Physiol Renal Physiol ; 319(4): F697-F711, 2020 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-32865013

RESUMO

Praliciguat, a clinical-stage soluble guanylate cyclase (sGC) stimulator, increases cGMP via the nitric oxide-sGC pathway. Praliciguat has been shown to be renoprotective in rodent models of hypertensive nephropathy and renal fibrosis. In the present study, praliciguat alone and in combination with enalapril attenuated proteinuria in the obese ZSF1 rat model of diabetic nephropathy. Praliciguat monotherapy did not affect hemodynamics. In contrast, enalapril monotherapy lowered blood pressure but did not attenuate proteinuria. Renal expression of genes in pathways involved in inflammation, fibrosis, oxidative stress, and kidney injury was lower in praliciguat-treated obese ZSF1 rats than in obese control rats; fasting glucose and cholesterol were also lower with praliciguat treatment. To gain insight into how tubular mechanisms might contribute to its pharmacological effects on the kidneys, we studied the effects of praliciguat on pathological processes and signaling pathways in cultured human primary renal proximal tubular epithelial cells (RPTCs). Praliciguat inhibited the expression of proinflammatory cytokines and secretion of monocyte chemoattractant protein-1 in tumor necrosis factor-α-challenged RPTCs. Praliciguat treatment also attenuated transforming growth factor-ß-mediated apoptosis, changes to a mesenchyme-like cellular phenotype, and phosphorylation of SMAD3 in RPTCs. In conclusion, praliciguat improved proteinuria in the ZSF1 rat model of diabetic nephropathy, and its actions in human RPTCs suggest that tubular effects may contribute to its renal benefits, building upon strong evidence for the role of cGMP signaling in renal health.


Assuntos
Apoptose/efeitos dos fármacos , Nefropatias Diabéticas/tratamento farmacológico , Agonistas da Guanilil Ciclase C/farmacologia , Túbulos Renais Proximais/efeitos dos fármacos , Nefrite/tratamento farmacológico , Pirazóis/farmacologia , Pirimidinas/farmacologia , Inibidores da Enzima Conversora de Angiotensina/farmacologia , Animais , Linhagem Celular , Citocinas/metabolismo , Nefropatias Diabéticas/metabolismo , Nefropatias Diabéticas/patologia , Modelos Animais de Doenças , Progressão da Doença , Enalapril/farmacologia , Humanos , Mediadores da Inflamação/metabolismo , Túbulos Renais Proximais/metabolismo , Túbulos Renais Proximais/patologia , Masculino , Nefrite/metabolismo , Nefrite/patologia , Fosforilação , Ratos Zucker , Transdução de Sinais , Proteína Smad3/metabolismo
12.
Medicine (Baltimore) ; 99(35): e21959, 2020 Aug 28.
Artigo em Inglês | MEDLINE | ID: mdl-32871945

RESUMO

BACKGROUND: Diabetic nephropathy (DN) is not only an important microvascular complication of diabetes but also the main cause of end-stage renal disease. Ginkgo biloba has a variety of biological activities and has been widely used in China to treat kidney diseases such as DN. This article aimed to evaluate the efficacy and safety of G biloba in patients affected with DN in the early stage. METHODS: This protocol follows the preferred reporting items for systematic review and meta-analysis protocols and the recommendations of the Cochrane Collaboration Handbook. Seven electronic databases will be searched from inception to July 31, 2020. Two investigators will independently identify relevant randomized controlled trials, fetch data, and assess the risk of bias with tools provided by Cochrane. A comprehensive meta-analysis will be conducted with the Cochrane Collaboration software (Review Manager 5.3) for eligible and appropriate studies. Further, the evidence will be assessed with the Grading of Recommendations Assessment, Development, and Evaluation approach. RESULTS: The results will be published in academic peer-reviewed journals, and the evidence gathered by this project will be dedicated to assessing the efficacy and safety of G biloba for DN patients in the early stage. CONCLUSION: This systematic review and meta-analysis will synthesize the available evidence to demonstrate the efficacy of G biloba in delaying the progression of patients with early DN. TRIAL REGISTRATION NUMBER: PROSPERO CRD42020166805.


Assuntos
Nefropatias Diabéticas/tratamento farmacológico , Ginkgo biloba , Fitoterapia , Extratos Vegetais/uso terapêutico , Humanos , Metanálise como Assunto , Revisões Sistemáticas como Assunto
13.
Zhongguo Ying Yong Sheng Li Xue Za Zhi ; 36(3): 207-210, 2020 May.
Artigo em Chinês | MEDLINE | ID: mdl-32981273

RESUMO

Objective: To observe the protective effects of exogenous spermine on renal fibrosis induced by diabetic nephropathy (DN) and to explore its mechanism.Methods: Twenty-four male C57 mice were randomly divided into control group, type 1 diabetes group (TID) and spermine pretreatment group (TID+Sp, n=8 in each group). TID mice were induced by STZ (60 mg/kg), and TID+Sp mice were pretreated with spermine (5 mg/(kg·d)) for 2 weeks before STZ injection. The mice were killed at the 12th week. The renal function was determined by serum creatinine and urea nitrogen. HE, PAS and Masson staining were used to evaluate renal tissue injury and fibrosis. The expressions of matrix metalloproteinase (MMP-2, MMP-9) and collagen IV (Coll-IV) in the kidney of mice were detected by Western blot. Results: Compared with the control group, the blood glucose (5.67±0.22 vs 28.40±0.57 mmol/L), creatinine (14.33±1.22 vs 30.67±4.73 µmol/L) and urea nitrogen (6.93±4.94 vs 22.00±1.04 mmol/L) in the T1D group were increased significantly (P<0.05), the glomerular basement membrane was thickened, the collagen was significantly increased, the expressions of MMP-2, MMP-9 and Coll-IV protein were increased (0.57±0.07 vs 1.06±0.20, 47.00±0.04 vs 1.29±0.09 and 0.42±0.16 vs 0.95±0.18,P<0.05). Exogenous spermine significantly alleviates the above-mentioned changes. Conclusion: Exogenous spermine pretreatment could significantly alleviate renal fibrosis in diabetic mice by regulating the balance between MMPs and collagen.


Assuntos
Diabetes Mellitus Experimental , Nefropatias Diabéticas , Espermina , Animais , Diabetes Mellitus Experimental/complicações , Diabetes Mellitus Experimental/tratamento farmacológico , Diabetes Mellitus Experimental/patologia , Nefropatias Diabéticas/complicações , Nefropatias Diabéticas/tratamento farmacológico , Nefropatias Diabéticas/patologia , Nefropatias Diabéticas/prevenção & controle , Fibrose/tratamento farmacológico , Regulação da Expressão Gênica/efeitos dos fármacos , Rim/patologia , Masculino , Camundongos , Distribuição Aleatória , Espermina/farmacologia , Espermina/uso terapêutico
14.
N Engl J Med ; 383(15): 1436-1446, 2020 10 08.
Artigo em Inglês | MEDLINE | ID: mdl-32970396

RESUMO

BACKGROUND: Patients with chronic kidney disease have a high risk of adverse kidney and cardiovascular outcomes. The effect of dapagliflozin in patients with chronic kidney disease, with or without type 2 diabetes, is not known. METHODS: We randomly assigned 4304 participants with an estimated glomerular filtration rate (GFR) of 25 to 75 ml per minute per 1.73 m2 of body-surface area and a urinary albumin-to-creatinine ratio (with albumin measured in milligrams and creatinine measured in grams) of 200 to 5000 to receive dapagliflozin (10 mg once daily) or placebo. The primary outcome was a composite of a sustained decline in the estimated GFR of at least 50%, end-stage kidney disease, or death from renal or cardiovascular causes. RESULTS: The independent data monitoring committee recommended stopping the trial because of efficacy. Over a median of 2.4 years, a primary outcome event occurred in 197 of 2152 participants (9.2%) in the dapagliflozin group and 312 of 2152 participants (14.5%) in the placebo group (hazard ratio, 0.61; 95% confidence interval [CI], 0.51 to 0.72; P<0.001; number needed to treat to prevent one primary outcome event, 19 [95% CI, 15 to 27]). The hazard ratio for the composite of a sustained decline in the estimated GFR of at least 50%, end-stage kidney disease, or death from renal causes was 0.56 (95% CI, 0.45 to 0.68; P<0.001), and the hazard ratio for the composite of death from cardiovascular causes or hospitalization for heart failure was 0.71 (95% CI, 0.55 to 0.92; P = 0.009). Death occurred in 101 participants (4.7%) in the dapagliflozin group and 146 participants (6.8%) in the placebo group (hazard ratio, 0.69; 95% CI, 0.53 to 0.88; P = 0.004). The effects of dapagliflozin were similar in participants with type 2 diabetes and in those without type 2 diabetes. The known safety profile of dapagliflozin was confirmed. CONCLUSIONS: Among patients with chronic kidney disease, regardless of the presence or absence of diabetes, the risk of a composite of a sustained decline in the estimated GFR of at least 50%, end-stage kidney disease, or death from renal or cardiovascular causes was significantly lower with dapagliflozin than with placebo. (Funded by AstraZeneca; DAPA-CKD ClinicalTrials.gov number, NCT03036150.).


Assuntos
Compostos Benzidrílicos/uso terapêutico , Taxa de Filtração Glomerular/efeitos dos fármacos , Glucosídeos/uso terapêutico , Insuficiência Renal Crônica/tratamento farmacológico , Inibidores do Transportador 2 de Sódio-Glicose/uso terapêutico , Idoso , Compostos Benzidrílicos/efeitos adversos , Compostos Benzidrílicos/farmacologia , Doenças Cardiovasculares/etiologia , Doenças Cardiovasculares/mortalidade , Doenças Cardiovasculares/prevenção & controle , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/tratamento farmacológico , Nefropatias Diabéticas/tratamento farmacológico , Feminino , Glucosídeos/efeitos adversos , Glucosídeos/farmacologia , Humanos , Estimativa de Kaplan-Meier , Falência Renal Crônica/mortalidade , Masculino , Pessoa de Meia-Idade , Análise de Regressão , Insuficiência Renal Crônica/complicações , Inibidores do Transportador 2 de Sódio-Glicose/efeitos adversos , Inibidores do Transportador 2 de Sódio-Glicose/farmacologia
16.
Nan Fang Yi Ke Da Xue Xue Bao ; 40(9): 1280-1287, 2020 Sep 30.
Artigo em Chinês | MEDLINE | ID: mdl-32990240

RESUMO

OBJECTIVE: To screen potential traditional Chinese medicine and their active monomer ingredients for treatment of diabetic nephropathy (DN) through the mechanism of caspase-1-mediated pyroptosis. METHODS: Using the Chinese Medicine System Pharmacology Analysis Platform (TCMSP), we screened traditional Chinese drugs and their active monomer components targeting caspase-1, and searched for the potential gene targets of the monomer components using GeneCards database. Cytoscape was used to construct the monomer compound-gene target network. Gene ontology (GO) functional enrichment analysis and Kyoto Gene and Gene Encyclopedia (KEGG) pathway enrichment analysis were used to predict the molecular mechanism of the screened traditional Chinese medicine and monomers. In SD rat models of diabetic mellitus (DM), we tested the therapeutic effect of ginsenoside Rh2 (daily dose of 20 mg/kg for 12 weeks) by examining renal pathology with HE staining and detecting the expressions of pyroptosis marker proteins caspase-1, GSDMD, IL-1ß and IL-18 in the renal tissues using Western blotting, the serum levels of IL-1ß and IL-18 and activities of cathepsin B and cathepsin L. RESULTS: Ginsenoside Rh2 could effectively dock with caspase-1 molecule. Fourteen targets were identified in ginsenoside Rh2 target network. GO function enrichment analysis revealed 27 GO terms associated with molecular function (4 terms), cell component (10 terms) and biological process (13 terms). KEGG pathyway enrichment analysis identified 4 signaling pathways involving lysosomes, glycosaminoglycan degradation, galactose metabolism, and sphingolipid metabolism pathways. In the animal experiment, treatment with ginsenoside Rh2 significantly alleviated renal pathologies and down-regulated the expressions of pyroptosis marker proteins (cleaved caspase-1, GSDMD-N, IL-1ß and IL-18) (P < 0.05 or 0.01), lowered serum levels of IL-1ß and IL-18 (P < 0.01), and enhanced the activities of cathepsin B and cathepsin L in the serum of the diabetic rats. CONCLUSIONS: Ginsenoside Rh2 may inhibit caspase-1-mediated pyroptosis through the lysosome pathway to improve kidney damages in rat models of DN.


Assuntos
Diabetes Mellitus Experimental , Nefropatias Diabéticas , Materia Medica , Animais , Caspase 1 , Diabetes Mellitus Experimental/tratamento farmacológico , Nefropatias Diabéticas/tratamento farmacológico , Proteínas de Neoplasias , Piroptose , Ratos , Ratos Sprague-Dawley
17.
Life Sci ; 261: 118455, 2020 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-32956662

RESUMO

Diabetic nephropathy (DN) is a chronic complication of diabetes mellitus (DM) with approximately 30-40% of patients with DM developing nephropathy, and it is the leading cause of end-stage renal diseases and diabetic morbidity. The pathogenesis of DN is primarily associated with irregularities in the metabolism of glucose and lipid leading to hyperglycemia-induced oxidative stress, which has been a major target together with blood pressure regulation in the control of DN progression. However, the regulation of 5' adenosine monophosphate-activated protein kinase (AMPK), a highly conserved protein kinase for maintaining energy balance and cellular growth and repair has been implicated in the development of DM and its complications. Therefore, targeting AMPK pathway has been explored as a therapeutic strategy for the treatment of diabetes and its complication, although most of the mechanisms have not been fully elucidated. In this review, we discuss the structure of AMPK relevant to understanding its allosteric regulation and its role in the pathogenesis and progression of DN. We also identify therapeutic agents that modulate AMPK and its downstream targets with their specific mechanisms of action in the treatment of DN.


Assuntos
Proteínas Quinases Ativadas por AMP/metabolismo , Regulação Alostérica/efeitos dos fármacos , Nefropatias Diabéticas/tratamento farmacológico , Descoberta de Drogas , Transdução de Sinais/efeitos dos fármacos , Animais , Nefropatias Diabéticas/metabolismo , Nefropatias Diabéticas/patologia , Humanos , Terapia de Alvo Molecular
18.
Phytomedicine ; 78: 153314, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32882582

RESUMO

BACKGROUND: Sarsasapogenin (Sar) shows good effects on diabetic nephropathy (DN) through inhibition of the NLRP3 inflammasome, yet the potential mechanism is not well known. PURPOSE: This study was designed to explore the regulation of thrombin and/or its receptor protease-activated receptor 1 (PAR-1) on the NLRP3 inflammasome and NF-κB signaling in DN condition, and further expounded the molecular mechanism of Sar on DN. METHODS: Streptozotocin-induced diabetic rats were treated by gavage with Sar (0, 20 and 60 mg/kg) for consecutive 10 weeks. Then urine and serum were collected for protein excretion, creatinine, urea nitrogen, and uric acid assay reflecting renal functions, renal tissue sections for periodic acid-Schiff staining and ki67 expression reflecting cell proliferation, and renal cortex for the NLRP3 inflammasome and NF-κB signaling as well as thrombin/PAR-1 signaling. High glucose-cultured human mesangial cells (HMCs) were used to further investigate the effects and mechanisms of Sar. RESULTS: Sar markedly ameliorated the renal functions and mesangial cell proliferation in diabetic rats, and suppressed activation of the NLRP3 inflammasome and NF-κB in renal cortex. Moreover, Sar remarkably down-regulated PAR-1 in protein and mRNA levels but didn't affect thrombin activity in kidney, although thrombin activity was significantly decreased in the renal cortex of diabetic rats. Meanwhile, high glucose induced activation of the NLRP3 inflammasome and NF-κB, and increased PAR-1 expression while didn't change thrombin activity in HMCs; however, Sar co-treatment ameliorated all the above indices. Further studies demonstrated that PAR-1 knockdown attenuated activation of the NLRP3 inflammasome and NF-κB, and Sar addition strengthened these effects in high glucose-cultured HMCs. CONCLUSION: Sar relieved DN in rat through inhibition of the NLRP3 inflammasome and NF-κB by down-regulating PAR-1 in kidney.


Assuntos
Nefropatias Diabéticas/tratamento farmacológico , Células Mesangiais/efeitos dos fármacos , Receptor PAR-1/metabolismo , Espirostanos/farmacologia , Animais , Glicemia/metabolismo , Células Cultivadas , Diabetes Mellitus Experimental/metabolismo , Nefropatias Diabéticas/metabolismo , Regulação para Baixo/efeitos dos fármacos , Humanos , Inflamassomos/efeitos dos fármacos , Rim/efeitos dos fármacos , Rim/metabolismo , Masculino , Células Mesangiais/metabolismo , NF-kappa B/metabolismo , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Nefrite/tratamento farmacológico , Nefrite/metabolismo , Ratos Sprague-Dawley , Receptor PAR-1/genética , Trombina/metabolismo
19.
Medicine (Baltimore) ; 99(31): e21137, 2020 Jul 31.
Artigo em Inglês | MEDLINE | ID: mdl-32756091

RESUMO

INTRODUCTION: A large number of patients with diabetic kidney disease (DKD) approach traditional Chinese medicine (TCM) owing to discontent with standard treatments. Based on TCM theory and clinical experience, the syndrome of kidney yin deficiency is a common type of DKD. Liuwei Dihuang pills (LDPs) is a common prescription of a Chinese herbal formula for patients presenting this syndrome of DKD. However, well-established data supporting the efficacy and safety of LDP in DKD treatment are lacking. METHODS: We have designed a double-blind, placebo-controlled, randomized trial. After a 2-week run-in period, 124 eligible participants with DKD will be assigned to either the experimental or the control group in a 1:1 ratio. Patients in the experimental group will receive LDP, while patients in the control group will receive a matched placebo. As the basic treatment in the 2 groups, metformin hydrochloride sustained-release tablets, for blood glucose control, and irbesartan tablets, for blood pressure regulation, will be provided. All participants will undergo 4 weeks of treatment and 12 weeks of follow-up. The primary outcome is the change in 24 hours urinary protein levels, measured from the baseline to the end of the treatment phase (week 24). The secondary outcomes to be assessed include the change in serum creatinine and estimated glomerular filtration rate, urinary albumin excretion rate, improvement of TCM syndromes and symptoms, fasting blood glucose and postprandial 2-hour blood glucose, blood lipids (total cholesterol, triglyceride, high-density lipoprotein cholesterol, and low-density lipoprotein cholesterol, from baseline to weeks 12 and 24. DISCUSSION: The results of this study will provide high-quality evidence of the effects of LDP in DKD treatment, which will provide an alternative treatment strategy in patients with DKD.


Assuntos
Diabetes Mellitus Tipo 2 , Nefropatias Diabéticas/tratamento farmacológico , Medicamentos de Ervas Chinesas/uso terapêutico , Falência Renal Crônica/tratamento farmacológico , Medicina Tradicional Chinesa , Adjuvantes Farmacêuticos , Adulto , Idoso , Creatinina/sangue , Nefropatias Diabéticas/sangue , Método Duplo-Cego , Feminino , Taxa de Filtração Glomerular , Humanos , Falência Renal Crônica/sangue , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Resultado do Tratamento
20.
Medicine (Baltimore) ; 99(34): e21923, 2020 Aug 21.
Artigo em Inglês | MEDLINE | ID: mdl-32846860

RESUMO

BACKGROUNDS: Diabetic kidney disease (DKD) is 1 of the common microvascular complications of diabetes, and the therapeutic effect of modern medicine on DKD is limited. At present, patented Chinese medicine Qizhijiangtang (QZJT) capsule has been widely used in the treatment of DKD. We aim to systematically assess the efficacy and safety of QZJT capsule for the treatment of diabetic kidney disease (DKD). METHODS: Randomized controlled trials of QZJT capsule for DKD treatment will be searched until July 1, 2020, in 7 electronic databases: PubMed, Embase, Cochrane Library, CNKI, Wanfang, VIP, and Chinese Biomedical Literature. Furthermore, additional relevant publications will be manually searched according to reference lists from the resulting publications. The Cochrane risk test from the Cochrane Handbook will be used as a bias tool to evaluate the methodological quality. The clinical efficacy will be the primary outcome, which is based on the changes in symptoms and levels of proteinuria. Review Manager 5.3 will be used to analyze the results. RESULTS AND CONCLUSIONS: Our meta-analysis will provide evidence to the clinical application of QZJT capsule in the treatment of DKD from the 4 aspects including the clinical efficacy, changes in proteinuria, the renal function and level of blood glucose. Meanwhile, the results can also reflect the role of traditional Chinese medicine in the treatment of DKD. PROSPERO REGISTRATION NUMBER: CRD42020153949.


Assuntos
Nefropatias Diabéticas/tratamento farmacológico , Medicamentos de Ervas Chinesas/uso terapêutico , Medicina Tradicional Chinesa/métodos , Glicemia/efeitos dos fármacos , Feminino , Humanos , Masculino , Proteinúria/tratamento farmacológico , Ensaios Clínicos Controlados Aleatórios como Assunto , Segurança , Resultado do Tratamento
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA