1.Research on network pharmacology of Acori Tatarinowii Rhizoma combined with Curcumae Radix in treating epilepsy.
Qian WANG ; Li-Li YUAN ; Yong-Ling ZHANG ; Wen-Tao FAN
China Journal of Chinese Materia Medica 2019;44(13):2701-2708
The chemical constituents and action targets of Acori Tatarinowii Rhizoma and Curcumae Radix were screened by network pharmacological method,and the mechanism of the combination of Acori Tatarinowii Rhizoma and Curcumae Radix in the treatment of epilepsy was analyzed. All chemical constituents of Acori Tatarinowii Rhizoma and Curcumae Radix were retrieved by TCMSP,and their action targets were screened. Component target PPI network was constructed. Epilepsy-related genes were retrieved from PharmGkb database,and PPI networks of disease targets were drawn by Cytoscape software. Cytoscape software was used to merge the network,screen the core network,and further analyze the gene GO function and KEGG pathway enrichment,which was verified by experimental research. One hundred and five chemical constituents of Acori Tatarinowii Rhizoma and 222 chemical constituents of Curcumae Radix were retrieved. Nineteen compounds were selected as candidate compounds according to OB and DL values. Among them,4 chemical constituents of Acori Tatarinowii Rhizoma and 15 chemical constituents of Curcumae Radix were found. A total of 88 target proteins were retrieved by retrieving TCMSP data,and PPI network was constructed. Through PharmGkb database,29 epilepsy-related genes were retrieved and disease target network was established. Cytoscape software and plug-ins were used for network merging and core network screening,and 69 genes were screened out. Through GO function analysis and KEGG pathway analysis,the mechanism of anti-epilepsy is related to prolactin signaling pathway,HTLV-Ⅰ infection signaling pathway,MAPK signaling pathway and herpes simplex infection signaling pathway. Further experimental verification showed that the serum prolactin level in epileptic rats was significantly increased. The neurons in hippocampal CA1 area degenerated,necrotized and lost 24 hours after epileptic seizure,and some neuron interstitial edema occurred. The possible mechanism of compatibility of Acori Tatarinowii Rhizoma and Curcumae Radix is related to serum prolactin level,MAPK signaling pathway,HTLV-Ⅰ infection and herpes simplex infection. The analysis may be related to viral encephalitis caused by HTLV-Ⅰ virus and herpes simplex infection,which damages nerve cells and causes seizures.
Acorus
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chemistry
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Animals
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CA1 Region, Hippocampal
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drug effects
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pathology
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Curcuma
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chemistry
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Drugs, Chinese Herbal
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pharmacology
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Epilepsy
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drug therapy
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Hippocampus
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Plant Roots
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chemistry
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Rats
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Rhizome
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chemistry
2.Malnutrition increases hippocampal neurogenesis in the immature rat after status epilepticus.
Yan-ling WANG ; Ruo-peng SUN ; Ge-fei LEI ; Bao-min LI ; Ji-wen WANG
Chinese Journal of Pediatrics 2003;41(1):17-20
OBJECTIVENeurogenesis in the dentate gyrus of hippocampus persists in brain of the immature and adult mammalian including human and it can be regulated by physiological and pathological events including nutritional status and seizures. The present study was designed to investigate the potential effects of malnutrition followed by status epileptics on hippocampal neurogenesis in the immature rat.
METHODSRat pups were divided into 4 groups: malnourished (M), nourished (N), malnourished plus seizures (MS) and nourished plus seizures (NS). The rat pups of group M and group MS were maintained on a starvation regimen from postnatal day 2 (P2) to P18. The status epilepticus of the rat pups in group MS and group NS was elicited by unilateral microinfusion of kainic acid (KA) into the amygdula at P15. Rat pups of the 4 groups were given bromodeoxyuridine (BrdU) intraperitoneally twice daily for 2 days beginning at P17. At P19, the rat pups were killed and the brains were processed for BrdU mitotic labeling combined with double-label immunohistochemistry using early neuron- or glia-specific markers TuJ1 (beta III tubulin) or GFAP (glial fibrillary acidic protein).
RESULTSThere were no significant differences in the latent time of seizure between group M and group N [(12.4 +/- 2.6) min vs. (12.1 +/- 2.9) min, P < 0.05]. Histological assessment did not reveal any evidence of hippocampal cell loss after status epilepticus in either group. BrdU-labeled cells were significantly higher in the rats of group MS (374 +/- 18) than group M (303 +/- 20), group NS (312 +/- 24) than group N (269 +/- 18), respectively (P < 0.01). There was also significant difference between group M and group N, group MS and group NS, respectively (P < 0.01). No significant difference was seen between the rats of group NS and group M (P > 0.05). Approximately 60% of BrdU-labeled cells coexpressed TuJ1, and 5% approximately 10% of those co-expressed GFAP.
CONCLUSIONEarly malnutrition do not alter KA seizure susceptibility and the behavioral manifestations of seizures at P15. Although malnutrition and status epilepticus can increase the proliferation of newly developed cells in the immature rat respectively, malnutrition followed by status epilepticus further increases this proliferation. Furthermore, most of newly developed cells differentiate into early neurons.
Animals ; Animals, Newborn ; Body Weight ; Bromodeoxyuridine ; metabolism ; Glial Fibrillary Acidic Protein ; analysis ; Hippocampus ; chemistry ; pathology ; Immunohistochemistry ; Malnutrition ; pathology ; Neurons ; chemistry ; pathology ; Rats ; Rats, Wistar ; Status Epilepticus ; chemically induced ; pathology ; Tubulin ; analysis
3.c-JUN Expression and Apoptotic Cell Death in Kainate-Induced Temporal Lobe Epilepsy.
Min Cheol LEE ; Jin Lee RHO ; Myung Kyu KIM ; Young Jong WOO ; Jae Hyoo KIM ; Sang Chae NAM ; Jung Jin SUH ; Woong Ki CHUNG ; Jai Dong MOON ; Hyung Ihl KIM
Journal of Korean Medical Science 2001;16(5):649-656
Following kainate (KA)-induced epilepsy, rat hippocampal neurons strongly ex-press immediate early gene (IEG) products, i.e., c-FOS and c-JUN, and neural stress protein, HSP72. Prolonged expression of c-JUN and c-FOS 48 hr after cerebral ischemia has been underwent delayed neuronal death. However, it is not yet clear whether IEGs actually assume the essential roles in the cell death process or simply as a by-product due to external stimuli because of the prolonged expression of c-FOS, more than one week, on intact CA2 neurons of the hippocampus in a KA-induced epilepsy model. This study investigated the relationships between prolonged expression of c-JUN and hippocampal neuronal apoptosis in a KA-induced epilepsy model. Epileptic seizure was induced in rats by a single microinjection of KA (1g/l) into the left amygdala. Characteristic seizures and hippocampal neuronal injury were developed. The expression of c-JUN was evaluated by immunohistochemistry, and neuronal apoptosis by in situ end labeling. The seizures were associated with c-JUN expression in the hippocampal neurons, of which the level showed a positive correlation with that of apoptosis. Losses of hippocampal neurons, especially in the CA3 region, were partly caused by apoptotic cell death via a c-JUN-mediated signaling pathway. This is thought to be an important component in the pathogenesis of hippocampal neuronal injury via KA-induced epilepsy.
Animal
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*Apoptosis
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Epilepsy, Temporal Lobe/chemically induced/*metabolism/pathology
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Hippocampus/*chemistry/pathology
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Immunohistochemistry
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Kainic Acid/*toxicity
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Male
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Proto-Oncogene Proteins c-jun/*analysis
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Rats
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Rats, Wistar
4.Effects of early environment on the expression of brain-derived neurotrophic factor and its receptor and brain development.
Chinese Journal of Contemporary Pediatrics 2012;14(9):703-707
OBJECTIVETo study the effect of early environment on the learning-memory ability of rats and the expression of brain-derived neurotrophic factor (BDNF) and its receptor, tyrosine kinase receptor B (TrkB), and to explore the influence of early environment on development of rat brain in developing stage and possible regulation mechanisms.
METHODSForty-five newborn Sprague-Dawley rats were randomly divided into three groups (15 rats in each group): enriched environment group (EE group), isolated environment group (IE group) and normal control group (NC group). The pups were nurtured separately in their groups. The learning-memory abilities of the rats were measured by "Y"-arm maze test 28 to 29 days after birth. The number of neural cells and the expression of BDNF and TrkB in the hippocampal CA3 and frontal lobe were were detected by Nissl's staining and immunohistochemistry respectively.
RESULTSThe results of the "Y"-arm maze test showed that rats in the EE group needed less training times, and retained a higher percentage of memory than the other two groups(P<0.01). Rats in the IE group needed more training times, and retained a lower percentage of memory than the NC group (P<0.01). By Nissl's staining, the numbers of neural cells in the hippocampal CA3 and frontal lobe were highest in the EE group followed by the NC group. They were lowest in the IE group (P<0.01). By immunohistochemistry, the expression of BDNF in the hippocampal CA3 and frontal lobe were highest in the EE group followed by the NC group. It was lowest in the IE group (P<0.01). Results were similar for expression of TrkB.
CONCLUSIONSEarly environment can affect the long-term brain development and brain function of rats by influencing the expression of BDNF and its receptor TrkB in the hippocampus and frontal lobe.
Animals ; Body Weight ; Brain ; growth & development ; Brain-Derived Neurotrophic Factor ; analysis ; Female ; Hippocampus ; chemistry ; pathology ; Male ; Maze Learning ; Rats ; Rats, Sprague-Dawley ; Receptor, trkB ; analysis ; Social Isolation
5.Effect of tacrolimus on growth-associated protein-43 expression in the hippocampus of neonatal rats with hypoxic-ischemic brain damage.
Yan ZHOU ; Ying XIONG ; San-Ying YUAN
Chinese Journal of Contemporary Pediatrics 2009;11(1):65-68
OBJECTIVEImmunosuppressant tacrolimus (FK506) has shown neuroprotective effects on hypoxic-ischemic brain damage (HIBD) in the adult animal model. This study investigated whether FK506 has a protection against HIBD in neonatal rats by examining growthjassociated protein-43 (GAP-43) expression in the hippocampus.
METHODSNinety-six seven-day-old Sprague-Dawley rats were randomly divided into three groups: sham-operation, HIBD and FK506 intervention group. HIBD was induced in the later two groups. The FK506 intervention group was intraperitoneally injected with FK506 immediately after HIBD, at a dosage of 1 mg/kg daily, for three days. The HIBD group was injected with normal saline. Immunohistochemical technical was applied to examine GAP-43 expression in the hippocampus 24 and 72 hrs and 7 and 14 days after HIBD.
RESULTSCompared with the HIBD group, hematoxylin-eosin staining showed attenuated neuronal necrosis in the FK506 intervention group. In the HIBD group, the expression of GAP-43 increased significantly 72 hrs, and 7 and 14 days after HIBD compared with that in the sham-operation group. The GAP-43 expression in the FK506 intervention group was significantly higher than that in the HIBD group 72 hrs and 7 days after HIBD.
CONCLUSIONSFK506 might have neuroprotective effects against HIBD in neonatal rats.
Animals ; Animals, Newborn ; GAP-43 Protein ; analysis ; Hippocampus ; chemistry ; drug effects ; Hypoxia-Ischemia, Brain ; drug therapy ; metabolism ; pathology ; Immunosuppressive Agents ; pharmacology ; Rats ; Rats, Sprague-Dawley ; Tacrolimus ; pharmacology
6.Influence of chronic lead exposure in rats during the developmental stage on expression of leptin in plasma, cerebrospinal fluid, and hippocampus.
Xue-Mei SHI ; Ya-Wen FU ; Lai-Rong HUANG ; Hui YANG
Chinese Journal of Contemporary Pediatrics 2016;18(8):762-769
OBJECTIVETo investigate the influence of lead exposure in rats during the developmental stage on the expression of leptin in plasma, cerebrospinal fluid, and hippocampus, as well as investigating whether leptin is associated with the mechanism of cognitive impairment induced by lead exposure.
METHODSThe rat model of cognitive impairment after chronic lead exposure was established by adding lead acetate into drinking water. According to the concentration of lead acetate in drinking water, the rats were divided into control (0 ppm), low-lead (50 ppm), medium-lead (200 ppm), and high-lead groups (1 000 ppm), with 16 rats in each group. Atomic absorption spectrometry was used to measure the content of lead in the plasma, cerebrospinal fluid and hippocampus. ELISA was used to measure the level of leptin in the plasma and cerebrospinal fluid. Immunohistochemistry was used to observe the distribution of leptin protein in the hippocampus. Western blot was used for relative quantification of leptin proteins in the hippocampus.
RESULTSCompared with the control group, the lead exposure groups showed significant increases in the content of lead in blood, cerebrospinal fluid, and hippocampus (P<0.01), as well as significant reductions in the levels of leptin in plasma and cerebrospinal fluid (P<0.05). The results of immunohistochemical staining showed that leptin was mainly distributed in the cytoplasm of pyramidal neurons in the hippocampal CA region. The results of Western blot showed that compared with the control group, the three lead exposure groups showed a slight increase in the protein expression of leptin in the hippocampus (P>0.05).
CONCLUSIONSLead exposure can reduce the levels of leptin in plasma and cerebrospinal fluid in rats, which may be associated with the mechanism of cognitive impairment induced by lead exposure.
Animals ; Apoptosis ; drug effects ; Cognition ; drug effects ; Female ; Hippocampus ; chemistry ; drug effects ; pathology ; Lead ; blood ; toxicity ; Leptin ; analysis ; blood ; cerebrospinal fluid ; Male ; Rats ; Rats, Sprague-Dawley
7.Effect of Angelica on hippocampal neurons and gliocytes of neonatal rats after intrauterine hypoxia.
Jing MA ; Cheng-Shi DING ; Hong YU
Chinese Journal of Applied Physiology 2012;28(4):362-364
Angelica
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chemistry
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Animals
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Animals, Newborn
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Cell Count
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Female
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Fetal Hypoxia
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pathology
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Hippocampus
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cytology
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drug effects
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Male
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Neuroglia
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cytology
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Neurons
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cytology
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Pregnancy
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Rats
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Rats, Sprague-Dawley
8.Overexpression of PDZ1 domain of PSD-95 protein rescues hippocampal neurons from apoptosis induced by oxygen-glucose deprivation.
Shu-Qun HU ; Yan-Yan ZONG ; Guang-Yi ZHANG
Acta Physiologica Sinica 2008;60(6):730-736
To detect the effect of PDZ1, domain of postsynaptic density 95 (PSD-95), on apoptosis of hippocampal neurons induced by oxygen-glucose deprivation (OGD), Sprague-Dawley rat hippocampal neurons were infected with PDZ1-viruses after 21 days of plating. Twenty-four hours after infection, cells were treated with OGD for 1.5 h, then were incubated with DAPI and apoptosis-like cells were characterized, or were collected for co-immunoprecipitation and Western blot analyses. The results showed that: (1) PDZ1 overexpression was observed in hippocampal neurons; (2) Apoptosis induced by OGD was obviously decreased in neurons overexpressing PDZ1 (P<0.05); (3) Overexpression of PDZ1 prevented the binding of GluR6 to PSD-95; (4) Overexpression of PDZ1 inhibited MLK3 and JNK1/2 activation induced by OGD. These results indicate that overexpression of PDZ1 may prevent hippocampal neurons from apoptosis induced by OGD.
Animals
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Apoptosis
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Cells, Cultured
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Culture Media
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chemistry
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Disks Large Homolog 4 Protein
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Glucose
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chemistry
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Hippocampus
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cytology
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Intracellular Signaling Peptides and Proteins
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metabolism
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Membrane Proteins
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metabolism
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Neurons
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cytology
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pathology
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Oxygen
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chemistry
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PDZ Domains
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Rats
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Rats, Sprague-Dawley
9.Effect of salvianolic acid B on neural cells damage and neurogenesis after brain ischemia-reperfusion in rats.
Jing ZHONG ; Min-ke TANG ; Yan ZHANG ; Qiu-ping XU ; Jun-tian ZHANG
Acta Pharmaceutica Sinica 2007;42(7):716-721
This study is to observe the effect of salvianolic acid B (Sal B) on neural cells damage and neurogenesis in sub-granular zone (SGZ) and sub-ventricular zone (SVZ) after brain ischemia-reperfusion (I/R) in rats. A modified middle cerebral artery occlusion (MCAO) model of focal cerebral ischemia-reperfusion was used. The rats were divided into four groups: sham control group, ischemia-reperfusion group, Sal B 1 and 10 mg x kg(-1) groups. Sal B was consecutively administrated once a day by ip injection after MCAO. The neurogenesis in SGZ and SVZ was investigated by BrdU method 7 days after MCAO. The Nissl staining for neurons in the hippocampal CA1 and cerebral cortex was performed 14 days after MCAO. A beam-walking test was used to monitor the motor function recovery. We found that brain ischemia resulted in an increase of BrdU positive cells both in ipsilateral SGZ and SVZ at 7th day after MCAO. Sal B (10 mg x kg(-1)) significantly increased further the number of BrdU positive cells both in SGZ and SVZ (P < 0.01). Ipsilateral hippocampal neuron damage occurred and CA1 almost lost 14 days after MCAO. Sal B (10 mg x kg(-1)) obviously attenuated the neuron damage and increased the number of neuron both in ipsilateral CA1 and cerebral cortex (P < 0.01). We also observed an obvious improvement of motor function recovery when Sal B (10 mg x kg(-1)) administrated. From the results above we concluded that Sal B stimulated neurogenesis process both in SGZ and SVZ after brain ischemia, and also alleviated neural cells loss and improved motor function recovery after brain ischemia in rats.
Animals
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Benzofurans
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isolation & purification
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pharmacology
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Cell Count
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Cerebral Cortex
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pathology
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Cerebral Ventricles
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pathology
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Dentate Gyrus
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pathology
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Hippocampus
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pathology
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Infarction, Middle Cerebral Artery
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complications
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Male
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Motor Activity
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drug effects
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Neurogenesis
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drug effects
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Neurons
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drug effects
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pathology
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Plants, Medicinal
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chemistry
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Random Allocation
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Rats
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Rats, Sprague-Dawley
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Reperfusion Injury
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etiology
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pathology
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physiopathology
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Salvia miltiorrhiza
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chemistry
10.Study on the anti-apopotosis induced by hypoxia/hypoglycemia and reoxygenation of panax notoginseng saponins in cultured rat hippocampal neurons.
Ling-Qun ZHU ; Ji-ping FAN ; Qi-fu HUANG ; Su-lun SUN ; Ying GAO ; Yi-huai ZOU ; Zhuang ZHANG ; Li-yun HE ; Hong ZHENG
China Journal of Chinese Materia Medica 2003;28(1):52-55
OBJECTIVETo study the inhibitory effects of Panax Notoginseng Saponins(PNS) on apoptosis induced by hypoxia/hypoglycemia and reoxygenation in cultured rat hippocampal neurons.
METHODApoptosis were measured by flow cytometry, intracellular free calcium concentration([Ca2+]i) was measured with confocal laser scanning microscopy, morphological changes and neuronal necrosis were observed with fluorescence microscope, and meanwhile the leakage of lactic dehydrogenase(LDH) was measured.
RESULTHypoxia/hypoglycemia cultures for 5 hours and reoxygenation induced neuronal apoptosis and necrosis, and significantly increased neuronal [Ca2+]i and the leakage of LDH. The effects were increased with the extending time of reoxygenation. PNS has could significantly decrease the percentage of neuronal apoptosis and necrosis, and reduce neuronal [Ca2+]i and the leakage of LDH.
CONCLUSIONPNS has inhibitory effect on neuronal apoptosis. This effect might be related to its effect of decreasing intracellular free calcium concentration.
Animals ; Apoptosis ; drug effects ; Calcium ; metabolism ; Cell Hypoxia ; Cells, Cultured ; Fetus ; Ginsenosides ; isolation & purification ; pharmacology ; Hippocampus ; cytology ; Hypoglycemia ; pathology ; L-Lactate Dehydrogenase ; metabolism ; Neurons ; cytology ; Panax ; chemistry ; Plants, Medicinal ; chemistry ; Rats ; Rats, Wistar