Protective effects of 3-n-butylphthalide on the cognitive dysfunction of chronic cerebral ischemic rats and its biochemical mechanisms / 中华老年医学杂志

Objective To investigate the protective effects of 3-n-butylphthalide (dl-NBP) on the cognitive dysfunction of chronic cerebral ischemic rats and its mechanism.Methods Old chronic cerebral ischemic rats (15 months) were modelized with ligating bilateral common carotid arteries for three months.Model rats were divided into four groups:sham,model,NBP 30 and 120 mg · kg-1 groups.The former and the latter two groups were administered vegetable oil and NBP for 45 days,respectively.Then,the cognitive function was measured in rats with Morris water maze.Meanwhile,the activities of superoxide dismutase (SOD),choline acetyltransferase (ChAT),true choline esterase (TChE),and the malondialdehyde (MDA) levels in brain cortex and hippocampus were detected with biochemical methods.Results During the five days of Morris water maze,the change of escape latency was from (57.7±3.8) s to (30.5±17.1) s in low dose of NBP group,and from (58.4±1.8) s to (28.9±11.3) s in high dose of NBP group as compared with no change from 60s to 60s in model group.Significant differences were found in escape latency between NBP's and model groups(P＜0.05 or 0.01).In spatial exploratory test,the time percentages spent in the platformquadrant were increased obviously in low and high doses of NBP [(26.0±6.9) ％ and (27.3±5.3) ％,respectively,P＜0.05],compared with that of model group.The SOD activity was obviously reduced in cortices of high dose of NBP group [(112.3 ± 7.6) U/mg protein] compared with that (134.6 ± 13.9) U/mg protein of model group (P＜0.01).The MDA contents were significantly reduced in cortices of low and high doses of NBP (2.39±0.31) nmol/mg protein and (1.56±0.19) nmol/mg protein,compared with that of model group (P＜0.01).The MDA contents in hippocampi of low and high doses of NBP [(0.71±0.10) nmol/mg protein and (0.83±0.05) nmol/mg protein] were also decreased significantly,compared with that of model group (P＜0.01).The ChAT level in cortex of high dose of NBP was increased significantly [(1615 ± 100) U/g protein,P＜0.05].The ChAT level in hippocampi of two doses of NBP also increased significantly [(1746±204) U/g protein and (1697± 117) U/g protein,P＜0.05].Conclusions NBP may improve cognition damage of chronic cerebral ischemic rats by ameliorating oxidative stress lesion and enhancing the activity of cholinergic nerve in brain tissue.

Effects of echinomycin on endothelin-2 expression and ovulation in immature rats primed with gonadotropins

Echinomycin is a small-molecule inhibitor of hypoxia-inducible factor-1 DNA-binding activity, which plays a crucial role in ovarian ovulation in mammalians. The present study was designed to test the hypothesis that hypoxia-inducible factor (HIF)-1alpha-mediated endothelin (ET)-2 expressions contributed to ovarian ovulation in response to human chorionic gonadotropin (hCG) during gonadotropin-induced superuvulation. By real-time RT-PCR analysis, ET-2 mRNA level was found to significantly decrease in the ovaries after echinomycin treatment, while HIF-1alpha mRNA and protein expression was not obviously changed. Further analysis also showed that these changes of ET-2 mRNA were consistent with HIF-1 activity in the ovaires, which is similar with HIF-1alpha and ET-2 expression in the granulosa cells with gonadotropin and echinomycin treatments. The results of HIF-1alpha and ET-2 expression in the granulosa cells transfected with cis-element oligodeoxynucleotide (dsODN) under gonadotropin treatment further indicated HIF-1alpha directly mediated the transcriptional activation of ET-2 during gonadotropin-induced superuvulation. Taken together, these results demonstrated that HIF-1alpha-mediated ET-2 transcriptional activation is one of the important mechanisms regulating gonadotropin-induced mammalian ovulatory precess in vivo.

Effect of NGF on tau hyperphosphorylation in rat hippocampus during focal cerebral ischemia-reperfusion / 中国药理学通报

Aim To explore the effect of exogenous nerve growth factor(NGF) on tau hyperphosphorylation in rat hippocampus during focal cerebral ischemia/reperfusion(I/R).Methods Focal cerebral ischemi-a/reperfusion model was induced by occlusion of the right middle cerebral artery using the intraluminal suture method.The level of tau hyperphosphorylation at Ser199/202 site and total tau in rat ispolateral hippocampal CA1 regions during focal cerebral ischemia/reperfusion were detected by SABC immunohistochemical method and Western blot,and the positive products were analyzed by image analysis system.Results The level of tau hyperphosphorylation at Ser199/202 site and total tau in rat hippocampal CA1 regions were significantly higher in I/R group than that in sham group(P

Upregulative effect of CGRP on expression of CREB and phospho-CREB protein during focal cerebral ischemia/reperfusion in rat parietal cortex / 中国病理生理杂志

AIM:To investigate the effect of calcitonin gene related peptide(CGRP)on the expression of cyclic AMP response element binding protein(CREB)and phosphorylated-CREB in rat parietal cortex during focal cerebral ischemia/reperfusion(I/R).METHODS:Focal cerebral ischemia/reperfusion model was induced by occlusion of the right middle cerebral artery using the intraluminal suture method.The expressions of CREB and phospho-CREB in the parietal cortex in different groups(sham group,focal cerebral ischemia/reperfusion group and CGRP group)were detected with immunohistochemistry and Western blotting,and the positive products were analyzed by image analysis system.RESULTS:There was definite expression of CREB in right parietal cortex in sham group,while it was lesser in I/R group than that in sham group,but it became more in CGRP group than that in I/R group(P

THE EFFECT OF CGRP ON THE EXPRESSION OF CREB mRNA IN RAT HIPPOCAMPUS AND PARIETAL CORTEX DURING FOCAL CEREBRAL ISCHEMIA AND REPERFUSION / 解剖学报

Objective To investigate the effect of calcitonin gene related peptide(CGRP) on the expression of cyclic AMP response element binding protein(CREB) mRNA in rat hippocampus and parietal cortex during focal cerebral ischemia and reperfusion(I/R). Methods Focal cerebral ischemia/reperfusion model was induced by occluding of the right middle cerebral artery using the intraluminal suture method.Hybridization in situ experiment was used to detect the expression of CREB mRNA in the ipsilateral hippocampal CA1 region and parietal cortex during different reperfusion periods.The positive product of CREB mRNA was analyzed by image analysis system. Results There was a distinct expression of CREB mRNA in right hippocampal CA1 region and parietal cortex in sham group.The absorbency of CREB mRNA positive product reduced in I/R group as compared to sham group,while it increased in CGRP group than I/R group(P

EFFECT OF CGRP AND NGF ON THE PHOSPHORYLATION OF CREB PROTEIN IN RAT HIPPOCAMPUS DURING FOCAL CEREBRAL ISCHEMIA/REPERFUSION / 解剖学报

Objective To investigate the effect of exogenous calcitonin gene related peptide(CGRP) and nerve growth factor(NGF) on the expression of cyclic AMP response element binding protein(CREB) and phosphorylated CREB(p-CREB) in rat hippocampus during focal cerebral ischemia/reperfusion(I/R). Methods Focal cerebral ischemia/reperfusion model was set up by occlusion of the right middle cerebral artery using the intraluminal suture method.The expression of CREB and p-CREB in the right hippocampus were detected with immunohistochemistrical SABC method and Western blotting.The immunoreactive positive products were analyzed by image analysis system. Results The expression of CREB decreased in I/R group as compared with sham group in right hippocampus,but the expression of p-CREB was higher in I/R group than that in sham group(P