RESUMO
Glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) receptor agonists have been shown to be neuroprotective in previous studies in animal models of Alzheimer's or Parkinson's disease. Recently, novel dual-GLP-1/GIP receptor agonists that activate both receptors (DA) were developed to treat diabetes. We tested the protective effects of a novel potent DA against middle cerebral artery occlusion injury in rats and compared it with a potent GLP-1 analog, Val(8)-GLP-1(glu-PAL). Animals were evaluated for neurologic deficit score, infarct volume, and immunohistochemical analyses of the brain at several time points after ischemia. The Val(8)-GLP-1(glu-PAL)-treated and DA-treated groups showed significantly reduced scores of neurological dysfunction, cerebral infarction size, and percentage of TUNEL-positive apoptotic neurons. Furthermore, the expression of the apoptosis marker Bax, the inflammation marker iNOS, and the survival marker Bcl-2 was significantly increased. The DA-treated group was better protected against neurodegeneration than the Val(8)-GLP-1(glu-PAL) group, and the scores of neurological dysfunction, cerebral infarction size, and expression of Bcl-2 were higher, whereas the percentage of TUNEL-positive neurons and the levels of Bax and iNOS were lower in the DA group. DA treatment reduced the infarct volume and improved the functional deficit. It also suppressed the inflammatory response and cell apoptosis after reperfusion. In conclusion, the novel GIP and GLP-1 dual-receptor agonist is more neuroprotective than a GLP-1 receptor agonist in key biomarkers of neuronal degeneration.
Assuntos
Encéfalo/efeitos dos fármacos , Peptídeo 1 Semelhante ao Glucagon/análogos & derivados , Receptor do Peptídeo Semelhante ao Glucagon 1/agonistas , Ataque Isquêmico Transitório/tratamento farmacológico , Lipopeptídeos/farmacologia , Receptores dos Hormônios Gastrointestinais/agonistas , Animais , Apoptose/efeitos dos fármacos , Apoptose/fisiologia , Encéfalo/metabolismo , Encéfalo/patologia , Modelos Animais de Doenças , Avaliação Pré-Clínica de Medicamentos , Peptídeo 1 Semelhante ao Glucagon/farmacologia , Receptor do Peptídeo Semelhante ao Glucagon 1/metabolismo , Infarto da Artéria Cerebral Média , Ataque Isquêmico Transitório/complicações , Ataque Isquêmico Transitório/metabolismo , Ataque Isquêmico Transitório/patologia , Masculino , Atividade Motora/efeitos dos fármacos , Degeneração Neural/tratamento farmacológico , Degeneração Neural/etiologia , Degeneração Neural/metabolismo , Degeneração Neural/patologia , Neurônios/efeitos dos fármacos , Neurônios/metabolismo , Neurônios/patologia , Fármacos Neuroprotetores/farmacologia , Óxido Nítrico Sintase Tipo II/metabolismo , Distribuição Aleatória , Ratos Sprague-Dawley , Receptores dos Hormônios Gastrointestinais/metabolismo , Proteína X Associada a bcl-2/metabolismoRESUMO
OBJECTIVE: To explore the influence of the storage conditions on the seed development of Corydalis yanhusuo. METHODS: The embryo formation process of the wild Corydalis yanhusuo was observed,and the germination rate of wild Corydalis yanhusuo seeds stored under different conditions was measured. RESULTS: The seed development of the wild Corydalis yanhusuo depended on the storage conditions. The seeds subjected to stratification had the highest germination percentage. Those stored in dry conditions would lose the vitality completely. The seeds in isothermal storage had very low germination rates. As revealed by slices, only the seeds after stratification treatment had the ability to form a complete embryo. CONCLUSION: The Corydalis yanhusuo seed is a kind of seed without fully developed embryo, and needs further after-ripening for its development. Its vitality has a great seasonal and annual dependence.