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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.
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Objective To investigate the regulation of B-lymphocyte stimulator(BLyS) levels in response to IFN-γand IL-6. Methods Flow cytometry, quantitative polymerase chain reaction, ELISA and Western blot were applied to examine the expression level of BLyS in response to IFN-γ and IL-6 . Results IFN-γand IL-6 induced BLyS expression in KM3 cells. After treated with BAY11-7082, an IkB-α phospho- rylation inhibitor, the up regulation of BI,yS induced by IFN-γ was completely inhibited. Inhibiting the nu-clear faetor-kB (NF-kB) and mitogen activated protein kinase(MAPK) activation in KM3 cells reduced BLyS protein and gene expression. Conclusion MAPK and NF-kB pathways are involved in the regulation of BLyS expression, which suggests that MAPK and NF-kB might be used for the treatment of multiple mye- loma.
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Objective To investigate the expression of neuronal extracellular signal-regulated kinase 1/2 (ERK1/2) and its significance after cerebral isehemia reperfusion in diabetic rats. Methods Seventy-two healthy adult SD rats were randomly divided into sham-operation, normal glucose with cerebral ischemia and diabetes with cerebral ischemia groups. Each group was redivided into ischemia 15 minutes and reperfusion 1, 3 and 6 h subgroups according to the different time points of ischemia reperfusion (n = 6 in each subgroup). Streptozocin was used to induce diabetes, and a global cerebral ischemia model of diabetic rat was established by the bilateral vascular occlusion combining with bloodletting, TUNEL and immunohistochemistry were used to observe neuronal apoptosis and the expression of the phosphorylation of ERK1/2 in hippocampal CA4 region. Results The incidences of neuronal apoptosis in hippocampal CA4 region for ischemia 15 minutes and reperfusion 1, 3 and 6 h in the diabetes with cerebral ischemia group were significantly higher than those in the normal glucose with cerebral ischemia group (P < 0. 05); the expressions of the phosphorylation of ERK1/2 at all time points in the diabetes with cerebral ischemia group were higher, and reperfusion 1 and 3 h were significantly higher than those in the normal glucose with cerebral ischemia group (P < 0.01). Conclusions ERK1/2 might involved in the mechanism of neuronal injury after diabetes aggravating cerebral ischemia-reperfusion.
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The effects of benazepril on P42/44MAPK, angiotensin Ⅱ expression in renal tissue and renal pathological change of the experimental diabetic rats were assessed and the possible mechanism of benazepril's renoprotective effect was explored. Adult male Wistar rats, 11-12 weeks age,weighing initially 160 to 200 g were randomly allocated into 2 groups: control group (A, n=6) and experimental group (n= 12). Diabetic rats in experimental group were rendered diabetic by intraperitoneal injection of Streptozotocin (60 mg/kg body weight), and randomly subdivided into B group (diabetic control) and C group (diabetic rats treated with benazepril, 6 mg/kg every day).Studies were performed 8 weeks after induction of diabetes. Twenty-four h urine of every rat was collected to detect urine creatinine. Serum glucose concentration and serum creatinine were determined by collecting blood samples from the inferior vena cava. Body and kidney weight were recorded. Creatinine clearance (Ccr) and ratio of kidney weight to body weight were calculated. Plasma and renal tissue angiotensin Ⅱ concentration was assayed by radioimmunoassay (RIA). The phospo-p44/42MAPK protein expression was detected by Western-blot. The results showed that benazepril had no significant effect on the blood glucose level in diabetic rats in two experimental groups.Ccr and ratio of kidney weight to body weight were increased in group B (P＜0. 01) as coapared with normal rats at the end of the 8th week. At the end of the 8th week, Ccr in group C was lower than that in group B (P＜0.01). The ratio of kidney weight to body weight in group C was lower than that in group B at the 8th week. There were glomeruli hypertrophy and slight or moderate mesangium proliferation in diabetic rats, while there was fragmentally proliferative mesangium in group C at the end of the 8th week. Renal tissue angiotensin Ⅱ concentration was significantly increased in group B, while benazepril could significantly decrease the concentration of angiotensin Ⅱ in renal tissue. The expression of the phospo-p44/42MAPK protein in group B was increased as compared with group A, while it was decreased in group C as compared with group B. P42/44MAPK pathway participated in the pathogenesis of diabetic nephropathy. Benazepril can eliminate high filtration of glomeruli, decrease proteinuria, and eliminate renal hypertrophy as well as renal destruction. Renoprotective effect of benazepril in diabetic rats may be partly related to the inhibition of angiotensin Ⅱ -P42/44MAPK pathway.