RESUMO
This study explored the mechanism of the ultrafiltration extract of Angelicae Sinensis Radix and Hedysari Radix in ameliorating renal fibrosis in the rat model of diabetic kidney disease(DKD) based on the expression of hypoxia-inducible factor-1α(HIF-1α)/vascular endothelial growth factor(VEGF) and HIF-1α/platelet-derived growth factor(PDGF)/platelet-derived growth factor receptor(PDGFR) signaling pathways in the DKD rats. After 1 week of adaptive feeding, 50 male SPF-grade Wistar rats were randomized into a blank group(n=7) and a modeling group. After 24 h of fasting, the rats in the modeling group were subjected to intraperitoneal injection of streptozocin and fed with a high-sugar and high-fat diet to establish a DKD model. After modeling, the rats were randomly assigned into model(n=7), low-dose ultrafiltration extract(n=7), medium-dose ultrafiltration extract(n=7), irbesartan(n=8), and high-dose ultrafiltration extract(n=8) groups. After intervention by corresponding drugs for 12 weeks, the general conditions of the rats were observed. The body weights and blood glucose levels of the rats were measured weekly, and the 24 h urinary protein(24hUP) was measured at the 6th and 12th weeks of drug administration. After the last drug administration, the renal function indicators were determined. Masson staining was employed to observe the pathological changes of the renal tissue. The expression of prolyl hydroxylase domain 2(PHD2) and HIF-1α in the renal tissue was detected by immunohistochemistry(IHC). Real-time qPCR was employed to determine the mRNA levels of PHD2, VEGF, PDGF, and PDGFR in the renal tissue. Western blot was employed to determine the protein levels of HIF-1α, VEGF, PDGF, and PDGFR in the renal tissue. The results showed that compared with the model group, drug administration lowered the levels of glycosylated serum protein(GSP), aerum creatinine(Scr), and blood urea nitrogen(BUN) in a dose-dependent manner(P<0.05 or P<0.01) and mitigated the pathological changes in the renal tissue. Furthermore, drug administration up-regulated mRNA level of PHD2(P<0.05 or P<0.01), down-regulated the mRNA levels of VEGF, PDGF, and PDGFR(P<0.05 or P<0.01) and the protein levels of HIF-1α, VEGF, PDGF, and PDGFR(P<0.01) in the renal tissue, and increased the rate of PHD2-positive cells(P<0.01). In conclusion, the ultrafiltration extract of Angelicae Sinensis Radix and Hedysari Radix effectively alleviated the renal fibrosis in DKD rats by inhibiting the expression of key proteins in the HIF-1α signaling pathway mediated by renal hypoxia and reducing extracellular matrix(ECM) deposition.
Assuntos
Nefropatias Diabéticas , Fator A de Crescimento do Endotélio Vascular , Ratos , Masculino , Animais , Ratos Wistar , Fator A de Crescimento do Endotélio Vascular/genética , Fator A de Crescimento do Endotélio Vascular/metabolismo , Ultrafiltração , Subunidade alfa do Fator 1 Induzível por Hipóxia/genética , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , Isquemia , Nefropatias Diabéticas/tratamento farmacológico , Nefropatias Diabéticas/genética , Fibrose , Hipóxia , Transdução de Sinais , RNA Mensageiro/metabolismoRESUMO
INTRODUCTION: Catheter-related infection (CRI) is a difficult clinical problem in renal medicine, with blood stream infections occurring in up to 40% of patients with haemodialysis (HD) catheters, conferring significant rates of morbidity and mortality. Several approaches have been assessed as a means to prevent CRI. Currently, an intervention that is the source of much discussion is the use of antimicrobial lock solutions (ALS). A number of past conventional meta-analyses have compared different ALS with heparin. However, there is no consensus recommendation regarding which type of ALS is best. The purpose of our study is to carry out a network meta-analysis comparing the efficacy of different ALS for prevention of CRI in patients with HD and ranking these ALS for practical consideration. METHODS AND ANALYSIS: We will search six electronic databases, earlier relevant meta-analyses and reference lists of included studies for randomised controlled trials (RCTs) that compared ALS for preventing episodes of CRI in patients with HD either head-to-head or against control interventions using non-ALS. Study selection and data collection will be performed by two reviewers independently. The Cochrane Risk of Bias Tool will be used to assess the quality of included studies. The primary outcome of efficacy will be catheter-related bloodstream infection (CRBSI). We will perform a Bayesian network meta-analysis to compare the relative efficacy of different ALS by WinBUGS (V.1.4.3) and STATA (V.13.0). The quality of evidence will be assessed by GRADE. ETHICS AND DISSEMINATION: Ethical approval is not required given that this study includes no confidential personal data and no data on interventions on patients. The results of this study will be submitted to a peer-review journal for publication. TRIAL REGISTRATION NUMBER: CRD42015027010.
Assuntos
Anti-Infecciosos/uso terapêutico , Infecções Relacionadas a Cateter/prevenção & controle , Diálise Renal , Adolescente , Adulto , Idoso , Cateterismo Venoso Central/efeitos adversos , Protocolos Clínicos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Ensaios Clínicos Controlados Aleatórios como Assunto , Resultado do Tratamento , Adulto JovemRESUMO
OBJECTIVE: To study the anti-asthmatic effects of Volatile oil of Radix Angelicae Sinensis (VOR, Traditional Chinese Medicine) on asthmatic BALB/c mice and its effect on Th17 cell immuno-activity through IL-17A and RORγt. METHODS: After grouping (n=12), the asthmatic BALB/c mice were replicated through injection of ovalbumin (OVA) for sensitization and administration of OVA aerosol for challenge and then, the asthmatic behaviors, respiratory function, lung histopathology as well as levels of IL-17A in serum and retinoid-related orphan receptor gamma t (RORγt) in lung tissue were observed after the action of VOR. RESULTS: VOR could maintain normal growth of body weight in asthmatic mice, improve asthmatic behaviors, respiratory function, lung histopathology and, inhibit over-expression of IL-17A and RORγt (P<0.05, 0.01) at 60, 120, 240 mg/kg doses. The combination of VOR and dexamethasone could bring synergistic effects on growth of body weight and expression of IL-17A and RORγt. CONCLUSIONS: VOR has significant effects of anti-asthma and one of the mechanisms is to inhibit immune activity of Th17 cell through relieving over-expression of IL-17 and RORγt. Besides, the combination of VOR and glucocorticoid could bring synergistic effects.
Assuntos
Antiasmáticos/farmacologia , Asma/tratamento farmacológico , Medicamentos de Ervas Chinesas/farmacologia , Óleos Voláteis/farmacologia , Células Th17/efeitos dos fármacos , Angelica sinensis , Animais , Líquido da Lavagem Broncoalveolar , Interleucina-17/sangue , Pulmão/patologia , Camundongos , Camundongos Endogâmicos BALB C , Membro 3 do Grupo F da Subfamília 1 de Receptores Nucleares/metabolismo , Ovalbumina , Células Th17/imunologiaRESUMO
OBJECTIVE: To study the effects of Volatile Oil of Radix Angelicae Sinensis (VOA) on experimental asthma in rat model based on abnormal immune functions of Treg cells. METHODS: After grouping, the asthmatic rats were developed through injecting OVA and AI(OH)3 for sensitization and then administering OVA aerosol for challenge, and the respiratory functions, asthmatic behaviors, IL-10 levels in bronchoalveolar lavage fluid (BALF) (ELISA) and Foxp3 expression (immunohistochemistry) in lung of asthmatic rats were observed. RESULTS: VOA at the doses of 40-160 mg/kg could improve the respiratory functions and the asthmatic behaviors, and upgrade IL-10 levels in BALF and Foxp3 expression in lung of asthmatic rats. CONCLUSION: VOA has some effects of anti-asthma and one of the mechanisms is to improving the lower immune functions of Treg cells.
Assuntos
Angelica sinensis/química , Asma/tratamento farmacológico , Óleos Voláteis/farmacologia , Óleos de Plantas/farmacologia , Animais , Líquido da Lavagem Broncoalveolar/química , Modelos Animais de Doenças , Fatores de Transcrição Forkhead/metabolismo , Interleucina-10/química , Pulmão/metabolismo , Ratos , Linfócitos T Reguladores/citologiaRESUMO
OBJECTIVE: To establish and evaluate a mouse model of bronchial asthma with Yin deficiency syndrome. METHODS: The mouse model of bronchial asthma with Yin deficiency syndrome was established by the treatment with injecting ovalbumin (OVA) two times to sensitize, inhaling OVA 14 times to stimulate, and using thyroxin through lavage during late stimulation. This model was evaluated through body weight, asthmatic behaviors, respiratory function, autonomous activity, lung pathology, and pulmonary fluid clearance. RESULTS: OVA combined with thyroxin was an appropriate method to induce the mouse model with increased food and water intake, autonomous activity, asthmatic behaviors score, and respiratory rate, decreased body weight, tidal volume, and wet/dry ratio of lung, and changed with pathology of lung tissue. The changes of the above mentioned parameters indicated that the model was the bronchial asthma with Yin deficiency syndrome. CONCLUSION: The OVA combined with thyroxin is a good pattern to establish a mouse model of bronchial asthma with Yin deficiency syndrome successfully, which can highly simulate the clinical symptoms of this disease.