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1.
Biochem Biophys Res Commun ; 715: 150006, 2024 Jun 30.
Artigo em Inglês | MEDLINE | ID: mdl-38678786

RESUMO

Vascular endothelial cells play a critical role in maintaining the health of blood vessels, but dysfunction can lead to cardiovascular diseases. The impact of arsenite exposure on cardiovascular health is a significant concern due to its potential adverse effects. This study aims to explore how NBR1-mediated autophagy in vascular endothelial cells can protect against oxidative stress and apoptosis induced by arsenite. Initially, our observations revealed that arsenite exposure increased oxidative stress and triggered apoptotic cell death in human umbilical vein endothelial cells (HUVECs). However, treatment with the apoptosis inhibitor Z-VAD-FMK notably reduced arsenite-induced apoptosis. Additionally, arsenite activated the autophagy pathway and enhanced autophagic flux in HUVECs. Interestingly, inhibition of autophagy exacerbated arsenite-induced apoptotic cell death. Our findings also demonstrated the importance of autophagy receptor NBR1 in arsenite-induced cytotoxicity, as it facilitated the recruitment of caspase 8 to autophagosomes for degradation. The protective effect of NBR1 against arsenite-induced apoptosis was compromised when autophagy was inhibited using pharmacological inhibitors or through genetic knockdown of essential autophagy genes. Conversely, overexpression of NBR1 facilitated caspase 8 degradation and reduced apoptotic cell death in arsenite-treated HUVECs. In conclusion, our study highlights the vital role of NBR1-mediated autophagic degradation of caspase 8 in safeguarding vascular endothelial cells from arsenite-induced oxidative stress and apoptotic cell death. Targeting this pathway could offer a promising therapeutic approach to mitigate cardiovascular diseases associated with arsenite exposure.


Assuntos
Apoptose , Arsenitos , Autofagia , Caspase 8 , Células Endoteliais da Veia Umbilical Humana , Estresse Oxidativo , Humanos , Arsenitos/toxicidade , Células Endoteliais da Veia Umbilical Humana/efeitos dos fármacos , Células Endoteliais da Veia Umbilical Humana/metabolismo , Apoptose/efeitos dos fármacos , Autofagia/efeitos dos fármacos , Caspase 8/metabolismo , Caspase 8/genética , Estresse Oxidativo/efeitos dos fármacos , Peptídeos e Proteínas de Sinalização Intracelular/metabolismo , Peptídeos e Proteínas de Sinalização Intracelular/genética , Proteólise/efeitos dos fármacos , Células Cultivadas
2.
Microbiome ; 12(1): 56, 2024 Mar 18.
Artigo em Inglês | MEDLINE | ID: mdl-38494479

RESUMO

BACKGROUND: Accumulating clinical evidence suggests that lung microbiome is closely linked to the progression of pulmonary diseases; however, it is still controversial which specimen type is preferred for the evaluation of lung microbiome. METHODS AND RESULTS: To address this issue, we established a classical acute lung injury (ALI) mice model by intratracheal instillation of lipopolysaccharides (LPS). We found that the bacterial DNA obtained from the bronchoalveolar lavage fluid (BALF), intact lung tissue [Lung(i)], lung tissue after perfused [Lung(p)], and feces of one mouse were enough for 16S rRNA sequencing, except the BALF of mice treated with phosphate buffer saline (PBS), which might be due to the biomass of lung microbiome in the BALF were upregulated in the mice treated with LPS. Although the alpha diversity among the three specimens from lungs had minimal differences, Lung(p) had higher sample-to-sample variation compared with BALF and Lung(i). Consistently, PCoA analysis at phylum level indicated that BALF was similar to Lung(i), but not Lung(p), in the lungs of mice treated with LPS, suggesting that BALF and Lung(i) were suitable for the evaluation of lung microbiome in ALI. Importantly, Actinobacteria and Firmicutes were identified as the mostly changed phyla in the lungs and might be important factors involved in the gut-lung axis in ALI mice. Moreover, Actinobacteria and Proteobacteria might play indicative roles in the severity of lung injury. CONCLUSION: This study shows both Lung(i) and BALF are suitable for the evaluation of murine lung microbiome in ALI, and several bacterial phyla, such as Actinobacteria, may serve as potential biomarkers for the severity of ALI. Video Abstract.


Assuntos
Lesão Pulmonar Aguda , Microbiota , Animais , Camundongos , Líquido da Lavagem Broncoalveolar/microbiologia , Lipopolissacarídeos , RNA Ribossômico 16S/genética , Pulmão/microbiologia , Lesão Pulmonar Aguda/induzido quimicamente , Lesão Pulmonar Aguda/tratamento farmacológico , Bactérias/genética
3.
Cell Death Dis ; 13(8): 733, 2022 08 25.
Artigo em Inglês | MEDLINE | ID: mdl-36008391

RESUMO

Ammonium tetrathiomolybdate (TTM) is a copper chelator in clinical trials for treatment of Wilson's disease, tumors and other diseases. In the current study, we innovatively discovered that TTM is a novel NRF2 activator and illustrated that autophagy contributed to TTM-induced NRF2 activation. We showed that TTM treatment promoted NRF2 nuclear translocation and upregulated transcription level of NRF2 target genes including HMOX1, GCLM, and SLC7A11 in vascular endothelial cells (HUVECs). Moreover, NRF2 deficiency directly hindered TTM-mediated antioxidative effects. Followingly, we revealed that overexpression of KEAP1, a negative regulator of NRF2, significantly repressed NRF2 activation induced by TTM. Further mutation analysis revealed that KEAP1 Cys151 is a major sensor responsible for TTM-initiated NRF2 signaling, suggesting that KEAP1 is involved in TTM-mediated NRF2 activation. Notably, we found that TTM can trigger autophagy as evidenced by accumulation of autophagosomes, elevation of LC3BI-II/I, increase of LC3 puncta and activation of AMPK/mTOR/ULK1 pathway. Autophagic flux assay indicated that TTM significantly enhanced autophagic flux in HUVECs. Inhibition of autophagy with knockout of autophagy key gene ATG5 resulted in suppression of TTM-induced NRF2 activation. TTM also induced phosphorylation of autophagy receptor SQSTM1 at Ser349, while SQSTM1-deficiency inhibited KEAP1 degradation and blocked NRF2 signaling pathway, suggesting that TTM-induced NRF2 activation is autophagy dependent. As the novel NRF2 activator, TTM protected against sodium arsenite (NaAsO2)-induced oxidative stress and cell death, while NRF2 deficiency weakened TTM antioxidative effects. Finally, we showed that autophagy-dependent NRF2 activation contributed to the protective effects of TTM against NaAsO2-induced oxidative injury, because of ATG5 or SQSTM1 knockout aggravated NaAsO2-induced elevation of HMOX1, cleaved PARP and γH2AX. Taken together, our findings highlight copper chelator TTM is a novel autophagy-dependent NRF2 activator and shed a new light on the cure for oxidative damage-related diseases.


Assuntos
Células Endoteliais , Fator 2 Relacionado a NF-E2 , Antioxidantes/metabolismo , Autofagia , Quelantes/farmacologia , Cobre/metabolismo , Cobre/farmacologia , Células Endoteliais/metabolismo , Proteína 1 Associada a ECH Semelhante a Kelch/genética , Proteína 1 Associada a ECH Semelhante a Kelch/metabolismo , Molibdênio , Fator 2 Relacionado a NF-E2/genética , Fator 2 Relacionado a NF-E2/metabolismo , Estresse Oxidativo , Proteína Sequestossoma-1/metabolismo
4.
J Nanobiotechnology ; 20(1): 149, 2022 Mar 19.
Artigo em Inglês | MEDLINE | ID: mdl-35305662

RESUMO

Copper oxide nanoparticles (CuONPs) are widely used metal oxide NPs owing to their excellent physical-chemical properties. Circulation translocation of CuONPs after inhalation leads to vascular endothelial injury. Mitochondria, an important regulatory hub for maintaining cell functions, are signaling organelles in responses to NPs-induced injury. However, how mitochondrial dynamics (fission and fusion) and mitophagy (an autophagy process to degrade damaged mitochondria) are elaborately orchestrated to maintain mitochondrial homeostasis in CuONPs-induced vascular endothelial injury is still unclear. In this study, we demonstrated that CuONPs exposure disturbed mitochondrial dynamics through oxidative stress-dependent manner in vascular endothelial cells, as evidenced by the increase of mitochondrial fission and the accumulation of fragmented mitochondria. Inhibition of mitochondrial fission with Mdivi-1 aggravated CuONPs-induced mtROS production and cell death. Furthermore, we found that mitochondrial fission led to the activation of PINK1-mediated mitophagy, and pharmacological inhibition with wortmannin, chloroquine or genetical inhibition with siRNA-mediated knockdown of PINK1 profoundly repressed mitophagy, suggesting that the protective role of mitochondrial fission and PINK1-mediated mitophagy in CuONPs-induced toxicity. Intriguingly, we identified that TAX1BP1 was the primary receptor to link the ubiquitinated mitochondria with autophagosomes, since TAX1BP1 knockdown elevated mtROS production, decreased mitochondrial clearance and aggravated CuONPs-induced cells death. More importantly, we verified that urolithin A, a mitophagy activator, promoted mtROS clearance and the removal of damaged mitochondria induced by CuONPs exposure both in vitro and in vivo. Overall, our findings indicated that modulating mitophagy may be a therapeutic strategy for pathological vascular endothelial injury caused by NPs exposure.


Assuntos
Mitofagia , Nanopartículas , Cobre/farmacologia , Células Endoteliais/metabolismo , Óxidos , Proteínas Quinases/genética , Proteínas Quinases/metabolismo
5.
Sensors (Basel) ; 21(19)2021 Oct 05.
Artigo em Inglês | MEDLINE | ID: mdl-34640938

RESUMO

This paper introduces a new device for gait rehabilitation, the gait propulsion trainer (GPT). It consists of two main components (a stationary device and a wearable system) that work together to apply periodic stance-phase resistance as the user walks overground. The stationary device provides the resistance forces via a cable that tethers the user's pelvis to a magnetic-particle brake. The wearable system detects gait events via foot switches to control the timing of the resistance forces. A hardware verification test confirmed that the GPT functions as intended. We conducted a pilot study in which one healthy adult and one stroke survivor walked with the GPT with increasing resistance levels. As hypothesized, the periodic stance-phase resistance caused the healthy participant to walk asymmetrically, with greatly reduced propulsion impulse symmetry; as GPT resistance increased, the walking speed also decreased, and the propulsion impulse appeared to increase for both legs. In contrast, the stroke participant responded to GPT resistance by walking faster and more symmetrically in terms of both propulsion impulse and step length. Thus, this paper shows promising results of short-term training with the GPT, and more studies will follow to explore its long-term effects on hemiparetic gait.


Assuntos
Transtornos Neurológicos da Marcha , Reabilitação do Acidente Vascular Cerebral , Adulto , Marcha , Humanos , Projetos Piloto , Caminhada
7.
Nucleic Acids Res ; 49(D1): D1268-D1275, 2021 01 08.
Artigo em Inglês | MEDLINE | ID: mdl-33270889

RESUMO

DNA methylation is an important epigenetic regulator in gene expression and has several roles in cancer and disease progression. MethHC version 2.0 (MethHC 2.0) is an integrated and web-based resource focusing on the aberrant methylomes of human diseases, specifically cancer. This paper presents an updated implementation of MethHC 2.0 by incorporating additional DNA methylomes and transcriptomes from several public repositories, including 33 human cancers, over 50 118 microarray and RNA sequencing data from TCGA and GEO, and accumulating up to 3586 manually curated data from >7000 collected published literature with experimental evidence. MethHC 2.0 has also been equipped with enhanced data annotation functionality and a user-friendly web interface for data presentation, search, and visualization. Provided features include clinical-pathological data, mutation and copy number variation, multiplicity of information (gene regions, enhancer regions, and CGI regions), and circulating tumor DNA methylation profiles, available for research such as biomarker panel design, cancer comparison, diagnosis, prognosis, therapy study and identifying potential epigenetic biomarkers. MethHC 2.0 is now available at http://awi.cuhk.edu.cn/∼MethHC.


Assuntos
Biomarcadores Tumorais/genética , Metilação de DNA , Bases de Dados Genéticas , Epigênese Genética , Regulação Neoplásica da Expressão Gênica , Neoplasias/genética , Biomarcadores Tumorais/metabolismo , DNA Tumoral Circulante/sangue , DNA Tumoral Circulante/genética , Variações do Número de Cópias de DNA , Progressão da Doença , Elementos Facilitadores Genéticos , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Internet , Análise em Microsséries , Anotação de Sequência Molecular , Mutação , Neoplasias/classificação , Neoplasias/diagnóstico , Neoplasias/metabolismo , Software , Transcriptoma
8.
J Ethnopharmacol ; 261: 113020, 2020 Oct 28.
Artigo em Inglês | MEDLINE | ID: mdl-32592886

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Danggui-Shaoyao-San (DSS), a well-known classic Traditional Chinese medicine (TCM) formula for enhancing Qi (vital energy and spirit), invigorating blood circulation and promoting diuresis, has been widely used in the treatment of nephrotic syndrome (NS). Previously, we have reported some protective effects of DSS against NS, but the in-depth mechanisms remain unclear. AIM OF THE STUDY: In this study, an ultra performance liquid chromatography coupled with quadrupole-time-of-flight mass spectrometry (UPLC-Q/TOF-MS)-based urinary metabonomics coupled with bioinformatics method was employed to evaluate the mechanisms of DSS in treating NS from the perspective of metabolism. MATERIALS AND METHODS: The rat models of NS were established using adriamycin injection. The regulative effects of DSS on NS in rats were first assessed by non-targeted metabonomics, which was based on UPLC-Q/TOF-MS. A series of target prediction models were used to predict the target of components identified in DSS and potential metabolites in NS, combined with the experimental results of metabonomics, to construct the biological network. RESULTS: A total of 16 potential metabolites were screened in NS, of which 13 were significantly regulated by DSS. Metabolic pathway analysis showed that the therapeutic effect of DSS on NS was mainly involved in regulating the amino acid metabolism and energy metabolism. The component-target-metabolites-pathway network revealed 29 targets associated with metabolites that were linked to 27 components of DSS. Bioinformatics analysis showed that the potential targets have various molecular functions (especially serine-type endopeptidase inhibitor activity) and biological process (such as positive regulation of peptidyl-tyrosine phosphorylation or autophosphorylation). CONCLUSIONS: The regulation of disrupted metabolic pathways and the relative targets may be the mechanism for DSS in the treatment of NS. Notably, metabonomics coupled with bioinformatics would be useful to explore the mechanism of DSS against NS and provide better insights on DSS for clinical use.


Assuntos
Medicamentos de Ervas Chinesas/farmacologia , Metabolismo Energético/efeitos dos fármacos , Rim/efeitos dos fármacos , Metaboloma/efeitos dos fármacos , Metabolômica , Síndrome Nefrótica/tratamento farmacológico , Animais , Biomarcadores/urina , Cromatografia Líquida de Alta Pressão , Biologia Computacional , Modelos Animais de Doenças , Doxorrubicina , Metabolismo Energético/genética , Redes Reguladoras de Genes , Rim/metabolismo , Masculino , Metaboloma/genética , Síndrome Nefrótica/induzido quimicamente , Síndrome Nefrótica/genética , Síndrome Nefrótica/urina , Mapas de Interação de Proteínas , Ratos Sprague-Dawley , Transdução de Sinais , Espectrometria de Massas por Ionização por Electrospray , Espectrometria de Massas em Tandem , Urinálise
9.
Appl Bionics Biomech ; 2019: 9765383, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31885690

RESUMO

Learning from demonstration (LfD) enables a robot to emulate natural human movement instead of merely executing preprogrammed behaviors. This article presents a hierarchical LfD structure of task-parameterized models for object movement tasks, which are ubiquitous in everyday life and could benefit from robotic support. Our approach uses the task-parameterized Gaussian mixture model (TP-GMM) algorithm to encode sets of demonstrations in separate models that each correspond to a different task situation. The robot then maximizes its expected performance in a new situation by either selecting a good existing model or requesting new demonstrations. Compared to a standard implementation that encodes all demonstrations together for all test situations, the proposed approach offers four advantages. First, a simply defined distance function can be used to estimate test performance by calculating the similarity between a test situation and the existing models. Second, the proposed approach can improve generalization, e.g., better satisfying the demonstrated task constraints and speeding up task execution. Third, because the hierarchical structure encodes each demonstrated situation individually, a wider range of task situations can be modeled in the same framework without deteriorating performance. Last, adding or removing demonstrations incurs low computational load, and thus, the robot's skill library can be built incrementally. We first instantiate the proposed approach in a simulated task to validate these advantages. We then show that the advantages transfer to real hardware for a task where naive participants collaborated with a Willow Garage PR2 robot to move a handheld object. For most tested scenarios, our hierarchical method achieved significantly better task performance and subjective ratings than both a passive model with only gravity compensation and a single TP-GMM encoding all demonstrations.

10.
Bol. latinoam. Caribe plantas med. aromát ; 18(3): 277-288, mayo 2019. ilus
Artigo em Inglês | LILACS | ID: biblio-1007989

RESUMO

Neurolaena lobata (L.) R.Br. ex Cass. (Asteraceae)Is a popular folk remedy for in Central America. The plant is of commercial value in Guatemala but so far there is not any monograph to guide regional laboratories on ensuring identity and chemical tests for this species. As identity test we here run macro and micro morphoanatomical studies of the characters of the vegetative organs. We also developed standard chemical tests for quality by both TLC and HPLC for infusions and tinctures of varying alcoholic strength. Their radical scavenging activities in DPPH and NO were also measured. Macro and micro morphoanatomical characters of the vegetative organs present a set of characteristics to facilitate the identification of dry powdered samples of this species. We developed optimal conditions for the TLC and HPLC phytochemical fingerprints of the 4 most common pharmacopoeial liquid herbal preparations from this herbal drug, namely infusion, 70%, 45% and 20% hydroalcoholic tinctures. Our work provides the Latin-American industry with a set of analyses to establish the identity and chemistry of N. lobata samples for quality control purposes.


Neurolaena lobata (L.) R.Br. ex cass. (Asteraceae) es un remedio popular popular en América Central. La planta tiene un valor comercial en Guatemala, pero hasta el momento no existe una monografía que guíe a los laboratorios regionales para garantizar la identidad y las pruebas químicas para esta especie. Como prueba de identidad proponemos estudios macro y micro morfoanatómicos de los caracteres de los órganos vegetativos. También desarrollamos pruebas químicas de calidad mediante CCF y CLAR para infusiones y tinturas de grado alcohólico variable. También se midieron sus actividades de captación de radicales en DPPH y NO. Los caracteres macro y micro morfoanatómicos de los órganos vegetativos presentan un conjunto de características para facilitar la identificación de muestras de polvo seco de esta especie. Desarrollamos condiciones óptimas para las huellas dactilares fitoquímicas de CCF y CLAR de las 4 preparaciones herbales líquidas farmacopéicas más comunes de esta droga herbal, a saber, infusión, 70%, 45% y 20% tinturas hidroalcohólicas. Nuestro trabajo proporciona a la industria latinoamericana un conjunto de análisis base para establecer la identidad y la química de las muestras de N. lobata con fines de control de calidad.


Assuntos
Asteraceae/anatomia & histologia , Asteraceae/química , Compostos Fitoquímicos/análise , Controle de Qualidade , Espectrofotometria Ultravioleta , Sequestradores de Radicais Livres , Cromatografia Líquida de Alta Pressão , Cromatografia em Camada Fina , Asteraceae/ultraestrutura , Guatemala , Microscopia
11.
Front Pharmacol ; 10: 232, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30949047

RESUMO

Schisandra chinensis is a commonly used traditional Chinese medicine, which has been widely used in the treatment of acute myocardial infarction in China. However, it has been difficult to systematically clarify the major pharmacological effect of Schisandra, due to its multi-component complex mechanism. In order to solve this problem, a comprehensive network analysis method was established based-on "component-gene ontology-effect" interactions. Through the network analysis, reduction of cardiac preload and myocardial contractility was shown to be the major effect of Schisandra components, which was further experimentally validated. In addition, the expression of NCOR2 and NFAT in myocyte were experimentally confirmed to be associated with Schisandra in the treatment of AMI, which may be responsible for the preservation effect of myocardial contractility. In conclusion, the three-mode gene ontology network can be an effective network analysis workflow to evaluate the pharmacological effects of a multi-drug complex system.

12.
Int J Mol Sci ; 18(9)2017 Aug 25.
Artigo em Inglês | MEDLINE | ID: mdl-28841143

RESUMO

Sheng-Mai-San (SMS) is a well-known traditional Chinese medicine (TCM) complex prescription used to treat heart failure (HF) and angina in clinic. However, its potential therapeutic mechanisms remain unclear. The present study evaluated the cardioprotection of extract of SMS (ESMS) on myocardial ischemia (MI)-induced HF, and explored the underlying molecular mechanisms. The results demonstrated that ESMS (728.0 mg/kg) significantly attenuated MI injury-induced HF by improving cardiac function and pathological changes, decreasing lactate dehydrogenase (LDH), creatine kinase (CK) activities, and brain natriuretic peptide (BNP) levels; increasing ATPase activity; and reducing intracellular Ca2+ levels in MI-induced HF mice model. It also significantly decreased the apoptotic index. In vitro, ESMS (400 µg/mL) inhibited mitochondrial-dependent myocardial apoptosis by modulating the expression of caspase-3 and the Bcl-2/Bax ratio, and improved mitochondrial function through increasing mitochondrial membrane potential and cellular ATP content. ESMS restored intracellular Ca2+ and downregulated the expression of Calcineurin A (CnA), thus inhibiting phosphorylation of dynamin-related protein 1 (Drp1) at Ser616 and increasing phosphorylation of Drp1 at Ser637 to prevent cardiomyocyte mitochondrial fission. Above-mentioned results demonstrated ESMS suppressed mitochondrial-mediated apoptosis in oxygen glucose deprivation (OGD) injured H9c2 cardiomyocytes. These findings suggested that ESMS attenuated MI-induced HF by regulating Ca2+ homeostasis and suppressing mitochondrial mediated apoptosis through the modulation of Ca2+-calcineurin-mediated Drp1 signaling pathways. Our results provide insight into the mechanism and clinical applications of SMS and suggest a potential therapeutic strategy for HF.


Assuntos
Calcineurina/metabolismo , Cálcio/metabolismo , Medicamentos de Ervas Chinesas/farmacologia , Dinaminas/metabolismo , Insuficiência Cardíaca/etiologia , Insuficiência Cardíaca/metabolismo , Isquemia Miocárdica/complicações , Isquemia Miocárdica/metabolismo , Transdução de Sinais/efeitos dos fármacos , Adenosina Trifosfatases/metabolismo , Animais , Apoptose/efeitos dos fármacos , Calcineurina/genética , Linhagem Celular , Modelos Animais de Doenças , Combinação de Medicamentos , Ecocardiografia , Expressão Gênica , Glucose/metabolismo , Insuficiência Cardíaca/diagnóstico , Insuficiência Cardíaca/tratamento farmacológico , Testes de Função Cardíaca , Masculino , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Camundongos , Mitocôndrias/metabolismo , Dinâmica Mitocondrial/efeitos dos fármacos , Miocárdio/metabolismo , Miocárdio/patologia , Oxigênio/metabolismo , Fosforilação , Transporte Proteico
13.
Theranostics ; 7(5): 1245-1256, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28435462

RESUMO

To achieve the best therapeutic efficacy and good prognosis, the drugs necessitate tailored profiles of excellent spatiotemporal control and therapeutic monitoring. Here we introduce a programmed theranostic nanoparticle with self-adapting properties for tumor-specific systemic treatment, including stealthy surface to prolong circulation time in blood, surface charge-reversion for tumor targeting, receptor-mediated internalization to increase intracellular accumulation, "proton sponge effect" for controllable drug release and escape from endo/lysosome. Encouragingly, in the process of drug-induced apoptosis, the therapeutic efficacy can be reported by fluorescence imaging in vivo, in situ and in real time. Therefore, this work provides a new paradigm for design of programmed theranositc nanomedicine and offers promising prospects for precise tumor treatment.


Assuntos
Antineoplásicos/administração & dosagem , Monitoramento de Medicamentos/métodos , Nanopartículas/administração & dosagem , Neoplasias/diagnóstico , Neoplasias/tratamento farmacológico , Nanomedicina Teranóstica/métodos , Antineoplásicos/farmacocinética , Microscopia Intravital/métodos , Imagem Óptica/métodos
14.
Zhongguo Zhong Yao Za Zhi ; 38(6): 871-4, 2013 Mar.
Artigo em Chinês | MEDLINE | ID: mdl-23717970

RESUMO

OBJECTIVE: To investigate the intervention effect of Danggui Shaoyao San on rats with cirrhotic ascites, and discuss the effect of arginine vasopressin (AVP) on cirrhotic ascites. METHOD: Male SD rats were randomly divided into the control group, the model group, Danggui Shaoyao San low, middle and high dose groups. The cirrhotic ascites rat model was established by CCl4 combined with phenobarbital. Their urines were collected at 24 h to observe urine excretion of each group. Filter papers were used to determine the amount of ascites. The levels of serum alanine aminotransferasa (ALT) , aspartate aminotransferase (AST) were detected by the automatic biochemistry analyzer. Plasma prothrombin time (PT) was evaluated by the blood coagulation analyzer. The concentration of AVP in plasma was detected by enzyme-linked immunosorbent assay (ELISA). Pathological changes in livers were observed by HE staining. RESULT: Compared with the model group, the Danggui Shaoyao San group showed significant improvement in live indexes, with notable decrease in serum ALT and AST and the time of PT, improvement in liver pathological changes. Simultaneously, the amount of ascites decreased to varying degrees, with notable increase in urine in 24 h and decrease in AVP concentration in plasma. CONCLUSION: Danggui Shaoyao San can notably improve liver functions of rats with cirrhotic ascites, reduce the generation of ascites and delay the progress of liver pathological changes. Its mechanism may be related to AVP.


Assuntos
Ascite/complicações , Ascite/tratamento farmacológico , Medicamentos de Ervas Chinesas/farmacologia , Cirrose Hepática/complicações , Animais , Arginina Vasopressina/sangue , Ascite/sangue , Ascite/fisiopatologia , Medicamentos de Ervas Chinesas/uso terapêutico , Fígado/efeitos dos fármacos , Fígado/enzimologia , Fígado/metabolismo , Fígado/fisiopatologia , Masculino , Ratos , Ratos Sprague-Dawley
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