RESUMO
Objective To investigate the effects of Edaravone on cognitive dysfunction and on protein expression of the mitogen-activated protein kinase/extracellular signal-regulated protein kinase (MAPK/ERK)signaling pathway in elderly patients with acute ischemic stroke. Methods A total of 100 elderly patients with acute ischemic cerebral stroke admitted to our hospital from January 2011 to December 2015 were enrolled in this study.During the corresponding period ,100 healthy individuals receiving regular check-ups were selected as the control group. The effects of Edaravone on cognitive function in elderly patients with acute ischemic cerebral stroke were assessed.Serum proteins related to the MAPK/ERK signaling pathway were assayed. Results Elderly patients with acute ischemic stroke showed obvious cognitive dysfunction ,and scores on memory ,orientation ,attention ,calculation language and recall significantly decreased(P＜0.01)but returned to normal after Edaravone treatment (P＜0.01).Compared with the control group ,serum protein expression of rat sarcoma (Ras) ,rapidly accelerated fibrosarcoma(Raf) ,hypoxia inducible factor-1α(HIF-1α) ,connective tissue growth factor (CTGF),extracellular signal-regulated protein kinase(ERK1),ERK2 ,MAPK/ERK kinase(MEK), interleukin-1(IL-1) ,tumor necrosis factor-α(TNF-α) ,vascular endothelial growth factor (VEGF) , tissue inhibitor of metalloproteinase (TIMP) ,nerve growth factor (NGF)and its receptors was significantly downregulated(P＜0.01) ,while expression of leptin and its receptors was upregulated in elderly patients with acute ischemic cerebral stroke ( P ＜ 0.01 ). Expression levels of the above downregulated proteins clearly recovered after Edaravone treatment ( P ＜ 0.01 ). Conclusions Edaravone has favorable effects on cognition dysfunction in elderly patients with acute ischemic cerebral stroke ,which may be related to the regulation of the MAPK/ERK signaling pathway.
RESUMO
ObjectiveTo study the effects of 6-hydroxydopamine (6-OHDA),and inhibitors for vesicular monoamine transporter (VMAT) on 5-hydroxytryptamine (5-HT),norepinephrine (NE) and dopamine (DA) and the expressions of tryptophan hydroxylase (TpH) mRNA,dopamine-beta-hydroxylase (DβH) mRNA and tyrosine hydroxylase (TH) mRNA in PC12 cells.Methods The cell viability was determined using MTT assay, the density of 5-HT, NE and DA was detected using enzyme-linked immunosorbent assay,and the expressions of TpHmRNA,DβHmRNA and THmRNA were detected using RT-PCR in PC12 cells at different time points (0,12,24,36,48 h )after exposure to different concentrations of 6-OHDA(25,50,100,200 μmol/L),and VMAT inhibitors,reserpine (50,100,400,1600 nmol/L),which combined with 6-OHDA( 100 μmol/L).Results (1)The cell viability declined with the increasing concentration of 6-OHDA which showed time dependence.The cell viability in PC12 cell which treated with reserpine decreased significantly in the responding group.The density of 5-HT in PC12 cell did not decrease with the increasing concentration of 6-OHDA,but the change had the time dependence,and the density of 5-HT was lowest at 36 h.The density of NE decreased with the increasing concentration of 6-OHDA which showed time dependence. The density of DA in PC12 cell decreased with the increasing concentration of 6-OHDA,but the change did not have the time dependence.The density of 5-HT,NE and DA in PC12 cell which treated with reserpine decreased significantly in the responding group. (2) The expressions of TpHmRNA, DβHmRNA and THmRNA in PC12 cell decreased with the increasing concentration of 6-OHDA which showed time dependence.The expressions of TpHmRNA(0.006 ± 0.001,0.003 ± 0.000,0.003 ± 0.000,0.002 ± 0.000) ; DβHmRNA (0.005 ± 0.002,0.003 ± 0.001,0.002 ±0.001,0.001 ± 0.000) and THm RNA (0.005 ± 0.002,0.003 ± 0.001,0.002 ± 0.001,0.001 ± 0.000) in PC12 cell which treated with reserpine decreased significantly in the responding group(F =13.336,9.000,9.393,all P =0.000).Conclusions6-OHDA can decrease the cell viability in PC12 cell,reduce the density of 5-HT,NE and DA and decrease the expressions of TpHmRNA,DβHmRNA and THmRNA,and the effects have dose and time dependence.Reserpine can aggravate this damage.