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Article in Chinese | WPRIM | ID: wpr-744253


AIM:To investigate the effects of Jiawei-Naotai formula (JWNTF) on ATF4/CHOP/Puma pathway in hippocampal neurons of ovariectomized female rats with cerebral ischemia.METHODS:The female rats were randomly divided into sham group, model group, JWNTF group and positive control group.The rats, expect in the sham group, were ovariectomized.The rats in each group were intragastric administration 11 days after ovariectomy.The rats in sham group and model group were given a gavage of 0.9%Na Cl, while the rats in other groups were administrated by corresponding therapy intragastrically for 3 d.The regional cerebral ischemia model was established by middle cerebral artery occlusion (MCAO) suture method 14 days after ovariectomy.The behaviors of the rats were evaluated 24 h after cerebral ischemia.The mRNA levels of Bax, Bcl-2 and caspase-3 were detected by RT-qPCR, and the protein expression of Bax, Bcl-2, caspase-3, ATF4, CHOP and Puma was determined by Western blot.RESULTS:Compared with sham group, the neurobehavioral scores significantly increased in other groups (P<0.05).Compared with model group, the neurobehavioral scores were significantly decreased in positive control group and JWNTF group (P<0.05).The protein expression of Bax, caspase-3, ATF4, CHOP and Puma, and the mRNA expression of Bax and caspase-3 in the hippocampus were much higher, and Bcl-2 was lower in model group than those in sham group (P<0.05).JWNTF significantly reduced the protein expression of Bax, caspase-3, ATF4 and CHOP, and the mRNA expression of Puma, Bax and caspase-3, and markedly increased the expression of Bcl-2 at mRNA and protein levels compared with model group.CONCLUSION:The JWNTF protects against brain damage induced by cerebral ischemia, which may be related to inhibitiing the expression of ATF4/CHOP/Puma pathway-related molecules at mRNA and protein levels.

Journal of Medical Postgraduates ; (12): 937-941, 2019.
Article in Chinese | WPRIM | ID: wpr-818351


Objective The occurrence of perimenopausal hot flashes involves many theories, among which the study of neurotransmitter mechanism has attracted much attention. This study aims to investigate the changes of α1 and α2 adrenoreceptors in the preoptic area of the hypothalamus(POAH) in ovariectomized rats after 4 weeks treatment with estradiol valerate, and explore the potential neurotransmitter mechanism of perimenopausal hot flashes. Methods 30 female Sprague-Dawley rats, weighing 230±10 g and aged 6-8WK, were divided into three groups: ovariectomy (OVX)group , sham group, and ovariectomy plus estradiol valerate (OVX+E2) group, each 10. Rats in sham-operated group opened pelvic cavity to find ovaries, but did not remove them. The other rats underwent bilateral ovariectomy under sterile conditions. Rats in OVX group and (OVX+E2) group received bilateral ovariectomy, rats in OVX group received isotonic saline gavage (10 mg/kg), and rats in (OVX+E2) group received estradiol valerate gavage (0.8 mg /kg). Anesthesia, cardiac perfusion and paraffin section were made after taking the brain. The expression of α1 and α2 adrenoreceptors in POAH of the rats was detected by immunohistochemistry. Results After 4 weeks’ treatment, the number of α1[(54.0±3.9)/100μm2] and α2[(89.0±2.4)/100μm2] adrenoreceptor positive cells in POAH of OVX group significantly decreased compared with that in sham group[(66.3±4.0)、(71.0±2.2)/100μm2](P<0.01),while the number of α1 and α2 [(63.7±4.5)、(73.1±3.5)/100μm2)] adrenoreceptor positive cells in POAH of(OVX+E2 )group significantly increased compared with that in OVX group(P<0.01). The difference was statistically significant. Conclusion The expression of two adrenergic receptors in the POAH of ovariectomized rats changed. The central noradrenergic system may be involved in the mechanism of perimenopausal hot flashes,which need further studying.

Article in Chinese | WPRIM | ID: wpr-702482


Objective To investigate the effect of Jiawei Naotaifang on neuronal apoptosis and the mechanism in ovariectomized rats with cerebral ischemia. Methods Female Sprague-Dawley rats(n=40)were randomly divided into sham group(n=10),model group(n=10),es-trogen group(n=10)and Jiawei Naotaifang group(n=10).The model group,estrogen group and Jiawei Naotai-fang group were ovariectomized.Eleven days after ovariectomy,the estrogen group and Jiawei Naotaifang group were given estrogen and Jiawei Naotaifang respectively intragastrically for three days.14 days after ovariecto-my,the model group,estrogen group and Jiawei Naotaifang group were modeled cerebral ischemia with Langa's method.24 hours after modeling,the apoptosis rate of neurons was detected with TUNEL,and the activation of extracellular signal-regulated kinase 1/2(ERK1/2)and c-Jun N-terminal kinase(p-JNK)in hippocampus were de-tected with Western blotting. Results Compared with the model group, the apoptosis rates decreased in Jiawei Naotaifang group and the estrogen group(P<0.001),with more activation of ERK1/2(P<0.01)and less activation of JNK(P<0.01). Conclusion Jiawei Naotaifang can protect neuron from apoptosis by promoting the activation of ERK1/2 and inhibiting the activation of p-JNK.

Chinese Pharmacological Bulletin ; (12): 428-432, 2018.
Article in Chinese | WPRIM | ID: wpr-705059


Aim To investigate the effects of Jiawei Naotaifang on cerebral infarction area, pathological changes of brain tissue and estrogen level of focal cere-bral Iischemia in female ovariectomized rats, and cor-relation between estrogen levels and cerebral infarction area. Methods SD rats were randomly divided into sham operation group, ovariectomized group, cerebral ischemia group,model group,and drug groups(estro-gen group, Jiawei Naotaifang high dose group, Jiawei Naotaifang middle dose group, Jiawei Naotaifang low dose group). The rats in the ovariectomized group, model group, drug groups were ovariectomized, elev-enth days after the ovariectomy. The rats in the drug groups were given intragastric administration for three days. The rats in the model group, cerebral ischemia group and drug groups were prepared for cerebral is-chemia models. Neurological function scores were scored 24 hours after the success of the model, serum levels of estrogen were detected, and the brain was stained with 2, 3, 5-triphenyltetrazolium chloride (TTC) and hematoxylin-eosin staining(HE), TTC staining was used to measure the area of cerebral in-farction, and HE staining was used to observe the pathological changes of brain tissues. Results Com-pared with cerebral ischemia group,cerebral infarction area of rats in the model group increased significantly, the estrogen level was lower and the necrosis and py-knosis of cortical and hippocampus cells of rats in the model group were more obvious. Compared with model group,the cerebral infarction area of rats in the drug groups was reduced,the estrogen levels were elevated, especially in Jiawei Naotaifang high dose group and es-trogen group. The cell morphology of rats,in the estro-gen group,Jiawei Naotaifang high dose group and mid-dle dose group, was improved obviously. Cerebral in-farction area was negatively correlated with the level of estrogen. Conclusions The cerebral infarction area of cerebral ischemia in female ovariectomized rat is signif-icantly correlated with the level of estrogen. Jiawei Naotaifang can reduce the damage and alleviate brain injury of cerebral ischemia in female ovariectomized rats,which may be related to the improvement of estro-gen level.

Article in English | WPRIM | ID: wpr-820513


OBJECTIVE@#To explore the significance of osteopontin and nuclear factor κB (NF-κB) expression in patients with knee osteoarthritis.@*METHODS@#RT-PCR and enzyme-linked immunosorbent assay were used to measure the Osteopontin (OPN) and NF-κB concentration of knee joint synovial fluid of patients with knee osteoarthritis and trauma fractures, and analyze the relationship between the expressiones of them.@*RESULTS@#OPN and NF-κB expression at the mRNA and protein levels of patients with knee osteoarthritis were significantly higher than the control group. the result showed statistical significance (P<0.05). There was a positive correlation between the OPN levels in synovial fluid of patients with knee osteoarthritis and NF-κB expression levels (P<0.05).@*CONCLUSIONS@#The high expression of OPN and NF-κB are closely related to occurrence and development of knee osteoarthritis.

Adult , Aged , Blotting, Western , Case-Control Studies , Female , Humans , Male , Middle Aged , NF-kappa B , Genetics , Metabolism , Osteoarthritis, Knee , Metabolism , Osteopontin , Genetics , Metabolism , Polymerase Chain Reaction , RNA, Messenger , Genetics , Metabolism , Statistics, Nonparametric , Synovial Fluid , Metabolism
Chinese Medical Journal ; (24): 414-419, 2008.
Article in English | WPRIM | ID: wpr-287722


<p><b>BACKGROUND</b>The mechanism of cerebral vasospasm following subarachnoid haemorrhage (SAH) is not understood. Here, we hypothesized that apoptosis of endothelial cells induced by p53 and its target gene em dash p53 upregulated modulator of apoptosis (PUMA) played an important role in development of cerebral vasospasm. We also observed the effects of a p53 inhibitor, pifithrin-alpha (PFT-alpha), on reducing the expression of p53 and PUMA, consequently decreasing the apoptosis of endothelial cells and alleviating cerebral vasospasm.</p><p><b>METHODS</b>Male Sprague-Dawley rats weighing 300-350 g were randomly divided into five groups: a control group (sham surgery), a SAH group, a SAH+dimethyl sulfoxide (DMSO) group, a SAH + PFT-alpha (0.2 mg/kg) group and a SAH + PFT-alpha (2.0 mg/kg) group. PFT-alpha was injected intraperitoneally immediately after SAH. Rats were sacrificed 24 hours after SAH. Western blot and immunohistochemical staining were used to detect the levels of p53, PUMA and caspase-3 protein. In addition, mortality and neurological scores were assessed for each group. Statistical significance was assured by analysis of variance performed in one way ANOVA followed by the Tukey test. The neurological and mortality scores were analyzed by Dunn's method and Fisher exact test, respectively.</p><p><b>RESULTS</b>After SAH, Western blot and immunohistochemical staining showed the levels of p53, PUMA and caspase-3 in the endothelial cells and the numbers of TdT mediated dUTP nick end labelling (TUNEL) positive endothelial cells were all significantly increased in the basilar arteries (P<0.05), but significantly reduced by PFT-alpha (P<0.05). These changes were accompanied by increasing diameters and declining wall thickness of basilar arteries (P<0.05), as well as reduced mortality and neurological deficits of the rats (P<0.05).</p><p><b>CONCLUSIONS</b>PFT-alpha could protect cerebral vessels from development of vasospasm and improve neurological outcome as well as reduce the mortality via suppressing apoptosis induced by p53 in the endothelial cells of cerebral vessels.</p>

Animals , Apoptosis , Benzothiazoles , Pharmacology , Therapeutic Uses , Blotting, Western , Disease Models, Animal , Endothelial Cells , Pathology , Male , Rats , Rats, Sprague-Dawley , Subarachnoid Hemorrhage , Drug Therapy , Pathology , Toluene , Pharmacology , Therapeutic Uses , Tumor Suppressor Protein p53 , Physiology , Vasospasm, Intracranial