Relationship between morphological changes of autophagy and apoptosis in PC12 cells induced by oxygen-glucose deprivation and reoxygenation / 中国病理生理杂志

[ ABSTRACT] AIM:To investigate the relationship between morphological changes of autophagy and apoptosis in the PC12 cells induced by oxygen-glucose deprivation and reoxygenation .METHODS:The PC12 cells were randomly di-vided into normal control group , oxygen-glucose deprivation and reoxygenation group , autophagy inhibitor group and auto-phagy activator group .The cells in oxygen-glucose deprivation and reoxygenation group , autophagy inhibitor group and au-tophagy activator group were exposed to reoxygenation (12 h) after 3 h of oxygen-glucose deprivation, and autophagy inhib-itor 3-methyladenine and autophagy activator rapamycin were added into the cells at the same time .Using transmission elec-tron microscope and monodansylcadaverine fluorescence staining , the morphological changes of autophagosome were ob-served.The apoptosis of the PC12 cells were analyzed by flow cytometry with Annexin V-FITC/PI staining and TUNEL method.RESULTS: Compared with normal control group , the numbers of autophagosomes and the apoptotic rates in-creased in oxygen-glucose deprivation and reoxygenation group (P<0.05).Compared with oxygen-glucose deprivation and reoxygenation group , the numbers of autophagosomes decreased obviously ( P<0.05 ) and the apoptotic rates increased markedly in autophagy inhibitor group (P<0.05).The numbers of autophagosomes increased obviously (P<0.05), the apoptotic rates decreased markedly ( P<0.05 ) , the autophagosomes became bigger in size , and autolysosomes was also found in autophagy activator group .CONCLUSION: Oxygen-glucose deprivation and reoxygenation induce autophagy in PC12 cells, and autophagy inhibits cell apoptosis to play a protective role .

Effects of astragaloside Ⅳ on apoptosis of PC12 cells induced by hypoxia/hypoglycemia and reoxygenation / 中国药理学通报

Aim To investigate the effects of astragalo-side IV on apoptosis of PC12 cells inducedby hypoxia/hypoglycemia and reoxygenation. Metheds PC12 cells were randomly divided into 4 groups: normal control group,hypoxia/hypoglycemia and reoxygenation group, astragaloside Ⅳ group and vehicle group. Hypoxia/hy-poglycemia and reoxygenation group, astragaloside Ⅳgroup and vehiclegroup were exposed to reoxygenation (12 h) after 3 h of oxygen and glucose deprivation, and astragaloside Ⅳ was added into cells at the same time. Inverted microscope was used to observe the morphological changes ofPC12 cells and MTT method to detect the activities of PC12 cells, and Annexin V-FITC/PI assay and TUNEL staining were used to meas-ure the apoptosis of PC12 cells. Results Compared with normal control group, cells became round or swol-len and its cellula processes were retracted or disap-peared in hypoxia/hypoglycemia and reoxygenation group;a large number of apoptotic cells could also be observed,whose nucleus were shrinkaged, fragmented or deep-stained. The activities of hypoxia/hypoglycemia and reoxygenation group were decreased markedly than those in normalcontrol group(P0. 05 ) . Conclusion Astragaloside IV can reduce the damage of PC12 cells induced by hypoxia/hypoglycemia and reoxygenation, increase cell activity and inhibit cell apoptosis.

Feasibility of nasal brain targeted drug delivery through the nose-brain channel in the nasal olfactory region using cimicifugoside H-1 / 中国组织工程研究

BACKGROUND:Recent studies have suggested that intranasal administration is one of the ways to target drugdelivery, and can effectively make the drug that cannot pass through the blood brain barrier by other pathways to bypass the blood brain barrier, resulting in targeted delivery to the brain. It provides a promising route for the treatment of central nervous system diseases. OBJECTIVE: To study the pharmacokinetic and brain-targeted channel-tropism tissue distribution character of cimicifugoside H-1 after nasal and intravenous administration in plasma and tissues in rats, in order to evaluate the feasibility of developing brain-targeted nasal delivery system of cimicifugoside H-1 by the passage between nose and brain in nasal olfactory area. METHODS: After intravenous injection and nasal administration of cimicifugoside H-1, the drug concentrations of plasma and channel-tropism organs (lung, spleen, stomach, large intestine, liver, kidney, brain, brain, cerebelum, cerebrospinal fluid, olfactory bulb and olfactory region) were detected. Drug-time curve was drawn. DAS program was used to select apartment model and pharmacokinetics parameters. RESULTS AND CONCLUSION:(1) The pharmacokinetics characters of cimicifugoside H-1 are rapidly absorbed and extensively distribution. Among major channel-tropism organs, drug concentrations were higher in the lung and brain than in the other organs. (2) Cimicifugoside H-1 could be straightly transported into brain by the intranasal administration. The molecule through olfactory mucosa in nasal cavity entered into olfactory bulb in arachno-hypostegal cavity, and then entered into olfactory region, cerebrospinal fluid, cerebrum and cerebelum gradualy. Olfactory bulb was the only way for drug molecule to go through nasal cavity into brain. (3) Compared with the intravenous injection, cimicifugoside H-1 through the intranasal administration has a significant

Effects of effective fraction of Epimedium,Astragalus,Radix Puerariae on the expression of DMT1 in the cerebral cortex of transgenic mice model of Alzheimer′s disease / 重庆医学

Objective To investigate the effects of Epimedium ,Astragalus ,Radix Puerariae on DMT1 expression in the cere‐bral cortex of APPswe/PS1ΔE9 double transgenic mice model of AD .Methods A total of 60 specific‐pathogen‐free male APPswe/PS1ΔE9 double transgenic mice aged 6 months were equally and randomly assigned to model ,Epimedium ,Astragalus ,Radix puerari‐ae ,compound and DFO groups .An additional 10 6‐month‐old C57BL/6J mice served as negative control group .Using immunohisto‐chemistry and molecular biology methods to investigate the effects of a compound combining the effective components of Epimedi‐um ,Astragalus ,Radix puerariae on DMT1 expression in the cerebral cortex of APPswe/PS1ΔE9 double transgenic mice model of AD . Results Immunohistochemical staining results revealed that DM T 1 positive cell did not show in negative control group .DM T1 ex‐pression was higher in model group compared with the negative control group .DMT1 expression was lower in the compound and deferoxamine groups than in the model group .No significant difference was detected in DM T 1 expression between deferoxamine and compound groups .RT‐PCR ,Western blot and immunohistochemical staining results showed no significant difference .Conclusion These compounds can downregulate DMT1 expression and inhibit iron overload in the cerebral cortex of mice with Alzheimer′s dis‐ease ,reduce iron overload induced impairment of the central nervous system .

Application frequency and therapeutic effect of Astragalus in treating ischemic cerebrovascular disease

In recent years, Traditional Chinese Medicine [TCM] therapy has achieved substantial progress and development, playing an important role in clinical practice. In this paper, to explore the therapeutic effect of Astragalus in treating ischemic cerebrovascular disease, 2687 patients with ischemic cerebrovascular disease who had been treated with Astragalus therapy from Jan 2014-Oct 2015 were selected as the research objects. Through retrospective analysis of their medical records, we analyzed the application frequency of Astragalus using quantitative method of information, and conducted specific analysis on the therapeutic effect of Astragalus after fully surveyed patients' physical conditions after treatment. Results show that in the treatment of ischemic cerebrovascular disease by TCM, Astragalus is of high application frequency and sound therapeutic effect, which is deserved to be applied and promoted in clinical practices

Improved suture occlusion method to prepare focal cerebral ischemia reperfusion models in Sprague-Dawley rats / 中国组织工程研究

BACKGROUND:During the progress of focal cerebral ischemia-reperfusion in rat with transient suture occlusion, bleeding combating and the line being plugged into the cerebral middle artery smoothly are important for successful modeling and research focus. OBJECTIVE:To improve Longa suture occlusion method for focal cerebral ischemia reperfusion model in Sprague-Dawley rats in order to establish a simple surgical procedure with low rate of intraoperative bleeding and high rate of successful models. METHODS:The two ends of the external carotid artery were clipped with electric knife, in addition to ligation of surgery lines intraoperatively;with the help of pincett, a fishing line was plugged into the carotid artery along the anteriomedialis artery wal (the direction of the internal carotid artery from the pterygopalatine arterial bifurcation). Postoperative behavior scores in rats, infarct volume calculation and histopathological evaluation under optical microscope were done. RESULTS AND CONCLUSION:Transverse sections of the external carotid artery were changed from a“O” shape to a“-”shape after being clipped with electric knife. Subsequently, line nodes were not easy to fal off any more, effectively preventing intraoperative bleeding. With the power of pincett, the rate of plugging the fishing line into artery was significantly increased. Rat’s neurological score and infarct volumes were significantly increased, and brain tissue pathological injury worsened. The modified suture occlusion method for focal cerebral ischemia reperfusion models effectively prevented line nodes off, successful y increased the rate of suture occlusion and models in Sprague-Dawley rats were developed successful y.

Effects of effective fraction of Epimedium,Astragalus,Radix Puerariae on behavioral and pathological changes in a transgenic mouse model of Alzheimer’s disease / 中国药理学通报

Aim To observe the effects of effective fraction of Epimedium,Astragalus,Radix Puerariae on behavioral and pathological changes in a transgenic mouse model of Alzheimer’s disease.Methods Six-month-old APPswe /PS1 ΔE9 transgenic mice were ran-domly divided into 2 groups:model group and effective fraction group,1 0 mice each group.The mice in the effective fraction group were treated with the effective fraction of Astragalus,Radix Puerariae,Epimedium compound for 8 weeks.The C57BL/6J mice were used as negative control group.After 8 weeks,the learning and memory function were measured by Morris water maze,the pathological changes in brain tissue were ob-served by Modified Bielschowsky staining and Nissl 's staining.Results During place navigation trial,the escape latency in the APPswe /PS1 ΔE9 double transgenic model mice was longer than those of the mice of C57 (P 0.05 ). The Modified Bielschowsky staining shows that the neuron fibers of the cerebral cortex of APPswe /PS1 ΔE9 double transgenic mice were enlarged,swelling,and dense.There were senile plaques and nerve fiber tangles in the cerebral cortex of APPswe /PS1 ΔE9 double transgenic mice.The neuron fibers of mice in the effective fraction group were relieved;there was a small amount of senile plaque.The Nissl’s staining shows that the neurons of the cerebral cortex of APPswe /PS1 ΔE9 mice were edema, the number of cells were decreased.The mice in the effective fraction group were free of the disease.Con-clusion The double transgenic APPswe /PS1 ΔE9 mice of AD can simulate the specific pathogenesis of AD, which may be the efficient experimental animal model. The effective fraction of epimedium,astragalus and ra-dix puerariae may have a neuroprotective effect against AD via improving the learning and memory ability,and reduce the cerebral cortex nerve fiber tangles,senile plaques and neurons edema changes.

The Effects of Astragalus Injection on the Morphology and Expression of Apaf-1 in Hippocampal Neurons after Cerebral Ischemia Reperfusion in Rats / 天津医药

Objective To investigate the effects of astragalus injection on the morphology and expression of Apaf-1 in hippocampal neurons after cerebral ischemia reperfusion in rats. Methods The male SD rats were randomly divided into 3 groups, sham-operated group, cerebral ischemia-reperfusion group (reperfusion group) and astragalus injection interven-tion group (experiment group). The global cerebral ischemia-reperfusion rat model was established by Pulsinelli four-vessel occlusion method. The astragalus injection group was intraperitoneally injected with astragalus 6 mL/kg, 30 mins before sur-gery and repeated every 24 h. Rat brains were removed 24 h after reperfusion in each group. HE staining was used to observe the pathological changes of the hippocampal neurons under the light microscope. The ultrastructural changes of hippocam-pal neurons were observed by transmission electron microscopy. Immunohistochemistry and Western blot methods were used to measure the expression of apoptotic protease activating factor-1(Apaf-1) protein. Results Compared with sham-operat-ed group, nuclear and mitochondrial damage was found in reperfusion group, and the expression of Apaf-1 protein increased obviously in hippocampus(Immunohistochemistry result:0.024 ± 0.001 vs 0.109 ± 0.011;Western blot result:0.270 ± 0.018 vs 0.894±0.072, P<0.01). Compared with reperfusion group, the damage in nuclear and mitochondria was relieved obviously in experiment group, and the expression of Apaf-1 protein in hippocampus was significantly decreased (Immunohistochemistry result:0.048±0.005;Western blot result:0.392±0.046, P<0.01). Conclusion Astragalus injection can reduce pathological damage of hippocampal neurons after cerebral ischemia and reperfusion in rats, and the mechanism is related with inhibiting of Apaf-1 protein.

β-amyloid protein up-regulates the expression of the receptor for advanced glycation end products by increasing ROS production / 南方医科大学学报

<p><b>OBJECTIVE</b>To investigate the mechanism of β-amyloid protein (Aβ) in regulating the expression of the receptor for advanced glycation end products (RAGE).</p><p><b>METHODS</b>Aβ1-40 was injected into the bilateral hippocampus of rats, and 3 weeks later, the levels of reactive oxygen species (ROS) production were detected by flow cytometry. The expressions of RAGE, reduced nicotinamide adenine dinucleotide phosphate (NADPH) oxidases (gp9l(phox) and p47(phox)), nuclear factor-κB (NF-κB), and inhibitor of κB (IκB) were measured by Western blotting.</p><p><b>RESULTS</b>Injection of Aβ1-40 caused a significant increase in the expressions of RAGE, gp9l(phox), p47(phox), phospho-p47(phox), phospho-IκBα, NF-κB and phospho-NF-κB in rat hippocampus but decreased the level of IκBα. Aβ1-40 injection also resulted in a significantly increased content of ROS in the hippocampus of the rats.</p><p><b>CONCLUSION</b>Aβ up-regulates the expression of RAGE in rat hippocampus via NADPH/ ROS/NF-κB signaling pathway.</p>

Effects of angiotensin II and its receptor blockers on migration and endothelin-1 expression of rat vascular adventitial fibroblast subpopulations / 药学学报

The study is to investigate the effect of angiotensin II (Ang II) and its receptor blockers on migration and endothelin-1 (ET-1) expression of rat vascular adventitial fibroblast subpopulations. Vascular adventitial fibroblasts were individually expanded by using cloning rings, and the effects of Ang II on the migration of adventitial fibroblast subpopulations were evaluated by Transwell. Fluorescence quantitative-PCR detected the expression of preproET-1 mRNA induced by Ang II, and its receptor antagonists losartan and PD-123319. The concentration of ET-1 was determined by ELISA. It showed that spindle shaped and epithelioid shaped cells were isolated by using cloning rings, named as spindle cells and round cells. RT-PCR showed that fibroblast subpopulations did not have leukocytes, endothelial cells and smooth muscle cells, namely pure cell lines. Compared with respective control cells, two subpopulations had transferring ability. Ang II significantly improved round cells migration in a concentration-dependent manner, and had no obvious influence on spindle cells migration. Ang II (1 x 10(-8) - 1 x 10(-6) mol x L(-1)) significantly increased the expression of preproET-1 mRNA in round cells (P < 0.01), and had no significant effect on the expression of preproET-1 mRNA in spindle cells. Losartan blocked the expression of preproET-1 mRNA induced by Ang II in round cells, and had no significant effect on the expression of preproET-1 mRNA in spindle cells. The effects of Ang II and ET-1 receptor inhibitors on the release of ET-1 were similar to the expression of preproET-1 mRNA. The results indicate that there are two cell subpopulations: round cells and spindle cells in rat vascular adventitial fibroblasts. Ang II significantly improved cells migration, and increased the expression of ET-1 in round cell subpopulation. It suggested that there may be different migratory mechanisms in two cell subpopulations, and the two subpopulations may play a different role in vascular remodeling and reparative process.

Effect of pathophysiology case-based learning(CBL)method on scores of pediatrics / 中华医学教育探索杂志

Objective To investigate the effect of pathophysiology case-based learning(CBL)method on scores of pediatrics.Methods Undergraduates from 2005 grade at Chengde medical college were divided into two groups:experimental group(n=138,CBL method)and control group(n=136,conventional teaching method).The scores of pediatrics between the two groups were compared.The pediatrics test paper was divided into two types:type B,which was tightly connected with the pathophysiology knowledge and type F,which had less connection with pathophysiology knowledge.The accuracy rates of both groups were compared.Correlation analysis on scores between pathophysiology and internal medicine,surgery,pediatrics,obstetircs and gynaecology was made.Results No significant difference in total scores of pediatrics was observed between the two groups(P＞0.05);total accuracy rate of experimental group was higher than that of control group(P＞0.05);similar total accuracy rates of type F test paper were observed in both groups(P＞0.05);positive correlations in scores between pathophysiology and internal medicine,surgery,pediatrics,obstetircs and gynaecology were found.Conclusions Satisfactory long-term effect are received by applying pathophysiological CBL model since it can promote the application of pathophysiological knowledge in pediatrics,however,no apparent effect on students'clinical ability can be obtained from the mere application of CBL in pathophysiology course.

Effect of nimodipine on DNA-binding activity of cAMP response element binding protein and CCAAT enhancer binding protein in hippocampus in vascular dementia rats / 中华行为医学与脑科学杂志

ObjectiveTo observe the effect of nimodipine on hippocampal DNA-binding activity change of cAMP response element binding protein ( CREB )and CCAAT enhancer binding protein (C/EBP) in a rat model of vascular dementia(VD),and to explore the treatment mechanism of nimodipine.Methods66 healthy adult male SD rats were assigned to the following three groups of 22 each:VD model group,Sham-operated group,Nimodipine group.VD rat model was prepared by four-vessel occlusion.Physiological saline solution( 8 ml · kg-1 · d-1 )and Nimodipine (20 mg· kg-1 · d-1 )were administered by gavage respectively.The Morris maze was adopted to detect the changes of spatial learning and memorizing capacity,while HE straining was adopted to observe the changes of pathological characteristics in hippocampal CA1 area,and electrophoretic mobility shift assay(EMSA) were adopted to observe DNA-binding activity changes of CREB and C/EBP in hippocampus tissue.ResultsThe Morris maze showed:the learning and memory ability of nimodipine group rats ( escape latency period ( 26.63 ± 1.31 )s,the times of cross-platform(7.25 ±0.92) times) was higher than that of VD model group(escape latency period (41.25 ± 1.83 ) s,the times of cross-platform ( 5.33 ± 0.64 ) times ),with difference of statistical significance (P ＜0.05).HE results:in VD model group,neurons in CA1 were scaltered and boundaries were unclear,nuclei region was stained,coagulation necrosis appeared,obviously cells lost.The CA1 neurons of nimodipine group returned to be normal,nuclear membrane's profile and nudeolus were clear,regularly arranged; the number of hippocampal normal neurons in nimodipine group (43.19 ± 2.87 ) was more than that of VD model group( 16.33 ± 1.09 ),with difference of statistical significance(P＜0.05 ).EMSA:both CREB and C/EBP DNA-binding activity in rat hippocampus of nimodipine group ( ( 369.75 ± 13.22 ),( 428.25 ± 17.69 ) respectively ) were higher than those of VD model group ( ( 142.25 ± 27.86 ),(97.00 ± 5.88 ),respectively),with difference of statistical significance (P ＜0.01 )).ConclusionNimodipine can improve VD rats hippocampal neuronal injuries and their learning and memory impairment may be involved in the upregulating CREB and C/EBP DNA-binding activity.

Astragalus injection inhibits the expression of JNK3 after hypoxia/hypoglycemia and reoxygenation in hippocampal neurons of rats / 中国药理学通报

Aim To investigate the effect of astragalus injection on the expression of JNK3(c-jun N terminal kinase)protein and JNK3 mRNA interrelated by apoptosis after hypoxia/hypoglycemia and reoxygenation in hippocampal neurons of rats.Methods The hippocampal neurons cultured for eight days were divided into four groups:normal control group,hypoxia/hypoglycemia and reoxygenation group,astragalus injection group and astragalus solution group.Hypoxia/hypoglycemia and reoxygenation group,astragalus injection group and astragalus solution group were treated with hypoglycemia and reoxygenation after being deprived of oxygen and glucose for 30 minutes.Methods of Western blot,ELISA and RT-PCR were used respectively to measure the expression of JNK3 mRNA after hypoxia/hypoglycemia and reoxygenation 0,0.5,2,6,24,72,120 h.Results Compared with normal control group,the mean optic density(MOD)of expression of JNK3 protein and activation of JNK3 protein in hippocampal neurons of rats every time points increased obviously in hypoxia/hypoglycemia and reoxygenation group except 120 h(P<0.05);compared with hypoxia/ hypoglycemia and reoxygenation group,MOD of expression of JNK3 mRNA and activation of JNK3 protein in hippocampal neurons of rats every time points decreased obviously except 120 h in astragalus injection group (P<0.05);compared with hypoxia/hypoglycemia and reoxygenation group,there was no difference in astragalus solution group.Compared with normal control group,MOD of expression of JNK3 mRNA in hippocampal neurons of rats every time points increased obviously in hypoxia/hypoglycemia and reoxygenation group(P<0.05);compared with hypoxia/ hypoglycemia and reoxygenation group,MOD of expression of JNK3 mRNA in hippocampal neurons of rats every time points decreased obviously in astragalus injection group except 120 h(P<0.05);compared with hypoxia/hypoglycemia and reoxygenation group,there was no difference in astragalus solution group.Conclusion Astragalus injection can inhibit the expression of JNK3 mRNA after hypoxia/hypoglycemia and reoxygenation,moreover,it can inhibit the expression of JNK3 protein and decrease the activation of JNK3 protein,accordingly it inhibits hippocampal neuronal apoptosis.

The effect of buyanghuanwu decoctinn on expression of immunoreactive protein and mRNA of NMDA receptor 2B subunit in rats hippocampal with vascular dementia / 中华行为医学与脑科学杂志

Objective To observe the effect of buyanghuanwu decoction on expression of immunoreactive protein and mRNA of NMDA receptor 2B subunit in rats hippocampal with vascular dementia to investigate the mechanism of buyanghuanwu decoction. Methods One hundred and forty-four rats were randomly divided into 4 groups: sham-operated group, VD model group,nimodipine group and buyanghuanwu decoction treatment group. The rats models of vascular dementia were built up by four vessels occlusion method. VD rats were treated with in-tragastrical buyanghuanwu decoction suspension (50 pharmacognostic g·kg-1·d-1) and nimodipine suspension (20 mg·kg-1·d-1) for 30 days. The learning and memory abilities were evaluated by Morris water maze tests. The change of NR2B protein in hippocampal of each group of rats were measured with immunohistochemistry and Western blot techniques and the expression of NR2B mRNA in hippocampus were observed by real-time fluorescence quantitative PCR techniques. Results Water maze tests,compared with sham-operated group((24. 18 ± 7.90)s,(7.99 ±1.32)/min) ,the escape latency(51. 25 ±18.28)s to explore the extension and the average spatial probe number ((5. 26 ±0. 74)/min) reduced in VD model group (P < 0. 05). Buyanghuanwu decoction ((25.91 ±9.56)s,(7. 52 ± 1. 27)/min) had significantly improved the above-mentioned rat model of learning and memory performance (P<0.05). There was no significant difference among sham-operated group,nimodipine group and buyanghuanwu decoction treatment group (P>0. 05). Similarly,as compared rats with sham-operated group(0.71 ±0.13), (5887 ±501), the expression of NR2B protein (0. 33 ± 0. 06) and its mRNA(593 ±53) were apparently decreased in VD rats (P< 0.05). The expression of NR2B protein(0.66 ±0. 11) and its mRNA (5692 ±482) in neuron of hippocampus were increased by buyanghuanwu decoction compared with the model group (P < 0. 05), and no difference was discovered between sham operation group and nimodipine group (P > 0.05).Conclusions Buyanghuanwu decoction improves the learning and memory abilities in VD rats, the therapeutic mechanism was concerned with lessening the injury of neurons on CA1 field in hippocampus and promoted the expression of NR2B protein and its mRNA.

Effect of cerebral ischemia-reperfusion injury on choline acetyltransferase activity related to study and memory in rat hippocampal tissue / 中国组织工程研究

BACKGROUND: The metabolism of acetylcholine in hippocampus reflects the function of cholinergic nervous system whose function is associated with learning and memory as well as intelligence.OBJECTIVE: To observe the changes of choline acetyltransferase activity in rat hippocampus after ischemia-reperfusion.DESIGN: Randomized controlled trial based on rats.SETTING: A Science and Research Department of Chengde Medical College.MATERIALS:The trial was conducted in the Central Laboratory of Chengde Medical College in 2002 and the subjects were 24 clean grade Wistar rats in equal number of the two sexes(weighting 260-280 g).METHODS:The 24 rats were randomly assigned into 3 groups: ① Model group:In this group the rats were made hyperlipemia and underwent bilateral carotid arteries blocking followed by reperfusion. ② Sham operation group:In this group the rats were made hyperlipemia and underwent only exposure of bilateral carotid arteries without ischemia-reperfusion. ③ Normal control group:In this group the rats received no intervention.The brains after the rats decapitated were harvested on the 1st 7th and 15th day respectively for colorimetric determination of the choline acetyltransferase activity in hippocampus.MAIN OUTCOME MEASURES:Determination of the choline acetyltransferase activity in the groups.RESULTS:None of the 24 rats was lost in the trial. ① The choline acetyltransferase activity in the model group on the 1st and 7th day was acetyltransferase activity in the model group on the 7th day was lower than that on the 1st and 7th day was lower than that in the normal controls[(0.037±0.006) μmol/g ·s, (0.017±0.006) μmol/g·s in model group vs (0.054±0.003) μ mol/g·s,(0.058±0.006) μmol/g·s in normal control group,P ＜ 0.01].② The choline acetyltransferase activity in the model group on the 7th day was lower than that on the 1st day. With repairing of ischemia-reperfusion injury,it recovered partially[(0.039±0.007) μnmol/g.s].③ Choline acetyltrans-ferase activity in sham operation group was not different from that in normal control(P ＞ 0.05).CONCLUSION:Simple exposure of carotid arteries does not change choline acetyltransferase activity.While ischemia-reperfusion can change the choline acetyltransferase activity and cause disorders of cholinergic nervous system function,which may be the reason for rat's intellectual disorders.

Effects of DAG-PKC signaling pathway on cAMP-PKA signaling pathway in anti-inflammatory effects of CCK-8 / 中国药理学通报

0.05).But PMA increased and SC-3088 decreased cAMP content and PKA activity in LPS-stimulated rat PIMs(P

Inhibitory effects of CCK-8 on NF-?B activities stimulated by LPS in rat PIMs / 中国病理生理杂志

AIM: To investigate the inhibitory effects of cholecystokinin octapeptide(CCK-8) on nuclear factor-?B(NF-?B) activities stimulated by lipopolysaccharide(LPS) by using forskolin,the activator of adenylate cyclase,and PKA inhibitor H-89 in rat pulmonary interstitial macrophages(PIMs).METHODS: PIMs were isolated and purified.EMDA was applied to detect NF-?B activities and Western blotting was used to analyze the I?B-? protein level in rat PIMs.RESULTS: The NF-?B activity was not detected in normal control rat PIMs.The NF-?B activity in LPS-treated rat PIMs was obviously higher than that in control group(P0.05).The NF-?B activity in CCK+LPS group and LPS+Fsk group were obviously lower than that in LPS group(P

The effect of buyanghuanwu decoction on expression of AMPA receptor GluR1 subunit in mRNA and protein levels in rat hippocampus with vascular dementia / 中国病理生理杂志

AIM:To observe the effect of buyanghuanwu decoction,a Chinese medicine,on the expression of AMPA receptor GluR1 subunit in mRNA and protein levels in rat hippocampus with vascular dementia (VD). METH-ODS:One hundred and forty -four rats were randomly divided into 4 groups:shamoperation group,VD model group,nimodipine group and buyanghuanwu decoction treatment group. The rat model of VD was built up by the method of 4 vessel occlusion. The VD rats were intragastrically treated with buyanghuanwu decoction suspension (pharmacognostic 50 g. kg -1.d -1) and nimodipine suspension (20 mg?kg -1.d-1) for 30 d. The learning and memory abilities were evaluated by Morris water maze testing. The change of GluR1 protein in hippocampal neurons in each group of rats was measured with immunohistochemistry and Western blotting techniques. The expression of GluR1 mRNA in hippocampus was determined by real -time fluorescence quantitative PCR. RESULTS:Compared to sham -operation group,the average escaping latency period (s) of Water maze tests in VD rats prolonged significantly and crossplatform time (numbers/min) shortened distinctly (P 0. 05). Compared to the rats in shamoperation group,the mRNA and protein levels of GluR1 were apparent-ly decreased in VD rats (P 0. 05). CONCLUSION:Buyanghuanwu decoction improves the learning and memory abilities in VD rats. The therapeutic mechanism is associated with lessening the neuron injury on CA1 field in hippocampus and restoring the mRNA and protein ex-pression of GluR1.

Activation of cAMP-PKA signal pathway by CCK-8 in rat pulmonary interstitial macrophages / 中国药理学通报

0.05); but significantly increased cAMP content and PKA activity at high concentration [(10-9~10-5) mol?L-1] (compared with normal control group:P

Function and relationship between c-Jun N-terminal kinase and caspase in apoptosis / 中国病理生理杂志

Apoptosis is important to the development of diseases. Research recently indicates that c-Jun N-terminal kinase (JNK) and cysteinyl aspartate-specific protease (caspase) play key roles in apoptosis and affect the development of diseases. This article is to introduce the function and relationship between JNK and caspase in apoptosis during the process of diseases.