RESUMO
Tumor radiotherapy induces hematopoietic organ damage and reduces thrombocyte counts. Thrombocytopenia is a common disease. Some studies have shown that tRNA synthetase plays not only catalytic tRNA aminoacylation roles, but also functions similarly to cytokines. Recombinant human tyrosyl-tRNA synthetase with a mutated Y341A (rhTyrRS (Y341A)) promotes megakaryocyte migrate from bone marrow to peripheral blood. It would promote megakaryocytes in the lungs adhering to vascular endothelial cells and resulting in the platelet production. The purpose of this research was to investigate the efficacy of rhTyrRS (Y341A) as a therapy for thrombocytopenia and to explore its mechanism of action. We found platelet number was effectively increased by rhTyrRS (Y341A) via platelet count and reticulated platelets (RPs) flow cytometry. We also demonstrated radiation-induced thrombocytopenia could be prevented by rhTyrRS (Y341A). The results of immunohistochemistry and H&E staining showed the number of pulmonary mature megakaryocytes was significantly increased in rhTyrRS (Y341A) treated groups. In transgenic zebrafish larvae, confocal microscopy results showed rhTyrRS (Y341A) promoted the migration and adhesion of megakaryocytes. These results suggested that rhTyrRS (Y341A) promote megakaryocytes in bone marrow migrating to lungs through blood circulation. rhTyrRS (Y341A) may be an effective medicine which could be used to treat patients suffering from thrombocytopenia.
Assuntos
Plaquetas/efeitos dos fármacos , Trombocitopenia/tratamento farmacológico , Trombopoese/efeitos dos fármacos , Tirosina-tRNA Ligase/administração & dosagem , Animais , Animais Geneticamente Modificados , Plaquetas/efeitos da radiação , Movimento Celular/efeitos dos fármacos , Modelos Animais de Doenças , Feminino , Células Endoteliais da Veia Umbilical Humana , Humanos , Masculino , Megacariócitos/efeitos dos fármacos , Megacariócitos/efeitos da radiação , Camundongos , Camundongos Endogâmicos C57BL , Mutação , Neoplasias/radioterapia , Contagem de Plaquetas , Radioterapia/efeitos adversos , Ratos , Ratos Sprague-Dawley , Proteínas Recombinantes/administração & dosagem , Proteínas Recombinantes/genética , Trombocitopenia/etiologia , Trombopoese/efeitos da radiação , Resultado do Tratamento , Tirosina-tRNA Ligase/genética , Peixe-ZebraRESUMO
Objective To investigate the distribution characteristics and risk factors of intracranial atherosclerotic stenosis ischemic stroke. Methods We retrospectively collected 342 consecutive patients with first-ever ischemic stroke. Clinical data was collected including demographics, the presence of risk factors,MRI with MRA and other routine admis?sion laboratory tests. Results Intracranial atherosclerotic stenosis (ICAS) was located most frequently in MCA (47.0%), Extracranial internal carotid artery was the most common affected artery (65.0%) among extracranial atherosclerotic steno? sis (ECAS). MetS (OR=1.586,95%CI:1.232~2.268), ApoB/ApoA1 ratio (OR=1.926,95%CI:1.051~4.288), were as?sociated with ICAS (vs ECAS), whereas hypertension (OR=3.603,95%CI:1.675~12.485), MetS (OR=2.268,95%CI:1.274~6.103), HbA1c (OR=2.015,95%CI:1.182~5.613) and ApoB/ ApoA I ratio (OR=1.948,95%CI:1.157~4.285) were related to ICAS (vs NCAS). Hypertension (OR=2.437,95%CI:1.492~3.505,P=0.005), Hcy (OR=2.437,95%CI:1.492~3.505,P=0.005) and HbA1c (OR=1.769,95%CI:1.034~3.121, P=0.005) were the independent risk factors re?lated to posterior circulation strokes (vs anterior circulation strokes ) in ICAS strokes. Conclusions The occurrence of ICAS may be more frequent than that of ECAS in ischemic stroke. Posterior circulation ICAS strokes seems to be close?ly associated with metabolic derangement.
