RESUMO
To explore the protective mechanism of simvastatin in acute lung injury (ALI), the lipopolysaccharide (LPS) induced (5â¯mg/kg) ALI rat model was used to examine the effects of simvastatin. Following simvastatin treatment, the histopathological evaluation of lung tissues was made using hematoxylin and eosin (H&E) staining. Also, myeloperoxidase (MPO) activity and the levels of tumor necrosis factor-alpha (TNF-α), interleukin-1 beta (IL-1ß), and IL-10 were determined by ELISA. Blood gas analyses of arterial blood samples were performed to assess the pulmonary gas exchange. Moreover, the neutrophil count and total protein content were determined in the bronchoalveolar lavage (BAL) fluid. The ratio of wet lung to dry lung (W/D) and the alveolar fluid clearance (AFC) were calculated to estimate the severity of edema. Lastly, the levels of A2BAR, CFTR, claudin4, and claudin18 were also measured by qRT-PCR and Western blotting. Simvastatin treatment, in a dose-related manner, markedly improved the lung histological injury and decreased the levels of TNF-α, IL-1ß, and increased IL-10 in LPS induced ALI. Also, pulmonary neutrophil count was alleviated. Besides, a decreased ratio of W/D lung also confirmed the simvastatin intervention. Notably, simvastatin reduced the levels of A2BAR, CFTR, and claudin18 but upregulated claudin4 in lung tissues. Additionally, treatment with PSB1115, an antagonist of A2BAR, countered the protective effect of simvastatin in ALI. Our study demonstrates that simvastatin has a protective effect against LPS-induced ALI by activating A2BAR and should be exploited as a novel therapeutic target for the treatment of ALI.
Assuntos
Lesão Pulmonar Aguda/prevenção & controle , Agonistas do Receptor A2 de Adenosina/farmacologia , Pulmão/efeitos dos fármacos , Receptor A2B de Adenosina/efeitos dos fármacos , Sinvastatina/farmacologia , Lesão Pulmonar Aguda/induzido quimicamente , Lesão Pulmonar Aguda/metabolismo , Lesão Pulmonar Aguda/patologia , Animais , Claudina-4/metabolismo , Claudinas/metabolismo , Regulador de Condutância Transmembrana em Fibrose Cística/metabolismo , Citocinas/metabolismo , Modelos Animais de Doenças , Mediadores da Inflamação/metabolismo , Lipopolissacarídeos , Pulmão/metabolismo , Pulmão/patologia , Masculino , Infiltração de Neutrófilos/efeitos dos fármacos , Edema Pulmonar/induzido quimicamente , Edema Pulmonar/metabolismo , Edema Pulmonar/patologia , Edema Pulmonar/prevenção & controle , Ratos Sprague-Dawley , Receptor A2B de Adenosina/metabolismo , Transdução de SinaisRESUMO
OBJECTIVE: To clone Aralia elata squalene synthase gene (designated as AeSS) and construct plant expression vector for transgenic research. METHODS: Isolated squalene synthase from Aralia elata with specific primers by RT-PCR and inserted AeSS gene into the plant expression vector pBI121. RESULTS: The full-length cDNA of AeSS (Genebank accession Number: GU354313) was 1 261 bp and contained a 1 245 bp open reading frame (ORF) encoding a polypeptide of 414 amino acids. The plant expression vector pAeSS was constructed by inserted AeSS gene into the downstream of 35 S promoter of plant expression vector pBI121. CONCLUSION: AeSS gene was cloned and plant expression vector was constructed for future research.
Assuntos
Aralia/genética , Farnesil-Difosfato Farnesiltransferase/genética , Vetores Genéticos/genética , Proteínas de Plantas/genética , Sequência de Aminoácidos , Aralia/enzimologia , Sequência de Bases , Clonagem Molecular , Primers do DNA , DNA Complementar/genética , Escherichia coli/genética , Expressão Gênica , Genes de Plantas , Dados de Sequência Molecular , Plasmídeos , Reação em Cadeia da Polimerase/métodos , Regiões Promotoras GenéticasRESUMO
OBJECTIVE: To study the rehabilitation effects ergometry on COPD patients. METHODS: Thirty COPD out-patients in our Hospital were randomly divided into 2 groups. Rehabilitation group, 15 patients, performed leg ergometry exercise of 80% peak Watt x 30min/d x 3d/w x 12w. Another 15 patients were control group without exercise. All patients received conventional therapy. Pulmonary function testing (PFT), cardiopulmonary exercise testing (CPET), arterial blood gas analysis (ABG), Borg and CAT sores were done at both baseline and 12 w. RESULTS: There was no statistically difference in lung function testing, blood gas analysis and cardiopulmonary exercise test when pre- exercises between 2 sub-groups. The IC, peak VO2 and peak, W of rehabilitation group significantly increased (P < 0.05); and Borg and CAT.scores significantly decreased (P < 0.05) from baseline; and other PFT and ABG did not change (P > 0.05). While there was no difference in control group (P > 0.05). CONCLUSION: Leg submaximal ergometry rehabilitation improves health condition and ameliorate dyspnea symptoms in COPD patients.