RESUMEN
Oxidative stress is a pivotal stimulating factor in neurocyte apoptosis and has been involved in the pathogenesis of Parkinson's disease (PD). In this study, we have demonstrated that the improvement in the motor disorder of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)/Pro-induced mice caused by b-Ecdysterone (b-Ecd) treatment is due to its antioxidant properties. Using open field, rotarod, and pole climbing tests, we have found that b-Ecd alleviates motor disorder in MPTP/Pro-induced mice and ultimately reduces the impairment of tyrosine hydroxylase (TH)-positive dopaminergic neurons in the substantia nigra (SN). Notably, these effects of b-Ecd were not observed in Nrf2-KO mice. In addition, b-Ecd significantly reduced the formation of ROS and the level of MDA, blocked the increase of LPO, and partially reversed the GSH/GSSG ratio in MPTP/Pro-induced WT mice; however, these results were also not observed in MPTP/Pro-induced Nrf2-KO mice. Mechanistically, b-Ecd enhanced the expression levels of heme oxygenase 1 (HO-1) and GCLc, but not NQO1 (NAD(P)H quinone dehydrogenase 1) and GCLm expression. Interestingly, b-Ecd failed to increase the protein and mRNA levels of HO-1 and GCLc in Nrf2-KO mice, suggesting that b-Ecd attenuates oxidative stress through an Nrf2-dependent mechanism. Furthermore, b-Ecd promoted the expressions of PI3K/Akt phosphorylation (activity) and GSK-3b phosphorylation (inactivity). Conversely, administration of b-Ecd markedly decreased Fyn phosphorylation levels. Collectively, our findings suggest that b-Ecd focuses on Nrf2 in reducing MPTP/Pro-induced oxidative stress and subsequent motor deficits by inhibiting its nuclear export through PI3K/Akt/GSK-3b/Fyn pathway regulation. These further indicate that b-Ecd may be an absorbing therapeutic agent for PD.
Asunto(s)
Ecdisterona , Factor 2 Relacionado con NF-E2 , Estrés Oxidativo , Trastornos Parkinsonianos , Animales , Ratones , Modelos Animales de Enfermedad , Neuronas Dopaminérgicas/efectos de los fármacos , Neuronas Dopaminérgicas/metabolismo , Ratones Endogámicos C57BL , Ratones Noqueados , Factor 2 Relacionado con NF-E2/metabolismo , Estrés Oxidativo/efectos de los fármacos , Trastornos Parkinsonianos/inducido químicamente , Trastornos Parkinsonianos/tratamiento farmacológico , Trastornos Parkinsonianos/metabolismo , Ecdisterona/farmacología , 1-Metil-4-fenil-1,2,3,6-Tetrahidropiridina/farmacologíaRESUMEN
Uniaxial compression experiments of limestone-coal specimens at different inclination angles (0, 15, 30, 45, and 60°) were conducted using acoustic emission and three-dimensional, extension test digital image correlation, and full-field strain measurement systems to examine how dip angles affect deformation failure. The findings indicate that: (1) specimen groups demonstrate plastic yield characteristics in the pre-peak stage. However, slight variations exist due to inclination angles. (2) The localization zone for deformation evolution closely correlates to primary crack initiation and propagation within coal specimens and to slipping at the rock's and coal's interface. Failure in the coal specimen triggers rebound deformation in limestone when the rock coal inclination angle is set at 15°. Both the rebound deformation amount and its rate exhibit upward trends as a function of the inclination angle. (3) The percentage of pre-peak elastic property density in the combined specimen is augmented from 98.56 to 88.08% as the inclination angle augments and reduces to 75.80%. External energy's conversion into missile performance shows an initial increase followed by a decrease. (4) The energy rate of the acoustic emission (AE) signal exhibits distinct temporal characteristics in the combined specimen that can be associated with quiet, active, and sudden increases.
