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Objective To explore the effects and mechanism of Baishile Capsules regulating SHH/Gli1 signaling pathway on hippocampal neurogenesis of depression model rats.Methods Totally 32 SD rats were randomly divided into control group,model group,fluoxetine(5.4 mg/kg)group and Baishile Capsules(2.88 g/kg)group,with 8 rats in each group.A depression rat model was established using chronic unpredictable mild stress and single cage feeding method.The model was established and administered simultaneously for 21 consecutive days.Depression-like behavior in rats were evaluated by sucrose preference experiment and open field experiment,ELISA was used to detect brain derived neurotrophic factor(BDNF)contents in rat serum and hippocampal tissue,the number of BrdU,BrdU/DCX,BrdU/NeuN positive cells in dentate gyrus of the hippocampus was observed by immunofluorescence,immunofluorescence and Western blot were used to detect the fluorescence intensity and protein expression of SHH,Gli1,Smo,Ptch in hippocampal tissue.Results Compared with the control group,the degree of sucrose preference significantly decreased in the model group(P<0.01),the number of horizontal and vertical movements significantly decreased(P<0.01),the contents of BDNF in serum and hippocampal tissue significantly decreased(P<0.05),the number of BrdU,BrdU/DCX,BrdU/NeuN positive cells in dentate gyrus of the hippocampus significantly decreased(P<0.01),and the fluorescence intensity and protein expression of SHH,Gli1,Smo,Ptch in hippocampal tissue significantly decreased(P<0.01,P<0.05).Compared with the model group,the degree of sucrose preference and the number of horizontal and vertical movements in fluoxetine group and Baishile Capsule group increased significantly(P<0.05,P<0.01),the contents of BDNF in serum and hippocampal tissue significantly increased(P<0.05,P<0.01),and the number of BrdU,BrdU/DCX,BrdU/NeuN positive cells in dentate gyrus of the hippocampus significantly increased(P<0.01,P<0.05),the fluorescence intensity and protein expressions of SHH,Gli1,Smo,Ptch in hippocampal tissue significantly increased(P<0.01,P<0.05).Conclusion Baishile Capsule can promote the hippocampus neurogenesis in depression model rats by regulating SHH/Gli1 signaling pathway,and play an antidepressant role.
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Background Pesticide poisoning is not only a common acute poisoning, but also an indispensable public health problem. It is important to describe and analyze the epidemic characteristics and trends of pesticide poisoning for its prevention and control. Objective To understand the epidemiological characteristics and trends of pesticide poisoning in Jiaxing from 2008 to 2020, and provide a basis for making effective intervention measures. Methods The relevant information of pesticide poisoning cases in Jiaxing from 2008 to 2020 was collected through the Occupational Disease and Occupational Health Information Monitoring System of the China Disease Prevention and Control Information System, and the demographic information was obtained from the statistical yearbook of Jiaxing. Joinpoint regression models were used to analyze trends in overall, gender, age, season, type of poisoning, and type of pesticide among poisoned individuals. Results A total of 3109 cases of pesticide poisoning were reported in Jiaxing City from 2008 to 2020. The overall pesticide poisoning incidence trended downward from 2008 to 2014, with an annual percent change (APC) of −9.0% (95%CI: −16.6%-−0.7%). The female pesticide poisoning incidence trended downward from 2008 to 2015, with an APC of −8.6% (95%CI: −13.9%-−2.9%). The 18-34 age group showed a decreasing trend of pesticide poisoning incidence from 2008 to 2015, with an APC of −11.0% (95%Cl: −17.4%-4.3%), and an increasing trend from 2015 to 2020, with an APC of 18.5% (95%Cl: 4.7%-34.0%). The >60 age group showed a decreasing trend of pesticide poisoning incidence from 2008 to 2014, with an APC of -12.9% (95%Cl: −20.4%-−4.7%). The second quarter showed an increasing trend of pesticide poisoning incidence from 2010 to 2020, with an APC of 4.4% (95%CI: 0.3%-8.5%); the third quarter showed a decreasing trend, with an APC of −4.9% (95%CI: −8.6%-−1.1%); the fourth quarter showed an increasing trend from 2015 to 2020, with an APC of 17.8% (95%CI: 4.4%-33.0%). Productive poisoning showed a decreasing trend, with an APC of −11.1% (95%CI: −16.2%-−5.7%); self-poisoning showed a decreasing trend from 2008 to 2014, with an APC of -9.5% (95%CI: −17.4%-−0.7%), and an increasing trend from 2014 to 2020, with an APC of 10.2% (95%CI: 0.5%-20.8%). The incidences of poisoning by herbicides, fungicides, and mixed formulations all showed an increasing trend from 2008 through 2020, with an APC of 8.6% (95%CI: 5.8%-11.5%), 9.1% (95%CI: 0.3%-18.7%), and 193.3% (95%CI: 11.6%-671.0%), respectively; the incidence of poisoning by other types of pesticides showed a decreasing trend from 2008 to 2020, with an APC of −14.1% (95%CI: −23.7%-−3.2%). Conclusion The overall reported pesticide poisoning incidents in Jiaxing City present a decline then a rise in 2008 to 2020. Relevant departments should take timely measures to prevent and reduce the occurrence of pesticide poisoning according to the changing characteristics and occurrence trends of local pesticide poisonings.
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[Abstract] Objective To explore the potential pathophysiological mechanism of depression by screening the expression profiles and competing endogenous RNA (ceRNA) regulatory network microRNA(miRNA), long non-coding RNA(lncRNA) and circular RNA (circRNA) in the hippocampus of chronic stress depression rat model. Methods Twelve SD rats were divided into blank group and model group. Chronic mild unpredictability stress (CUMS) was used to construct the rat model of depression. The whole transcriptome analysis was performed on the hippocampus of the rats, and the possible regulatory networks among lncRNA-miRNA-mRNA and circRNA-miRNA-mRNA were explored by bioinformatics method. Results According to the | fold change | ≥1. 5 and P≤0. 05, 29 differentially expressed miRNAs (21 up-regulated and 8 down-regulated), 686 differentially expressed lncRNAs (163 up-regulated and 523 down-regulated) and 8 differentially expressed circRNAs (3 up-regulated and 5 down-regulated) were identified. Gene Ontology (GO) and Kytot Encyclopedia of Genes and Genomes(KEGG) pathway analysis showed that the target genes of miRNAs were mainly enriched in the Golgi apparatus and calcium ion binding process in the cell membrane, the functions of lncRNAs target genes involved nucleic acid binding regulation, cytokine and protein ubiquitination, etc, and the functions of host genes of circRNAs were associated with cellular stimulation response, metabolic process, catalytic activity and other processes. The ceRNA network of lncRNAs and circRNAs showed complex interactions between non-coding RNA (ncRNA) and mRNA related to synaptic plasticity, such as protein Wnt-sa(WNT5a) and collagentype III alpha1(COL8a1) related to axon orientation and laminin A2(LAMA2) related to neurodevelopment. Conclusion The ceRNA network of lncRNA and circRNA shows that the complex interaction betweens ncRNA and mRNA is highly associated with the neuroplasticity, which support the neuroplasticity hypothesis of depression.
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OBJECTIVE@#To investigate the effect of Zuogui Jiangtang Jieyu Decoction (ZJJ) on Shh signaling and self-renewal of neural stem cells in the hippocampal dentate gyrus of diabetic rats with depression.@*METHODS@#Diabetic rat models with depression were randomly divided into model group, positive drug (metformin + fluoxetine) group, and low-, medium-, and high-dose ZJJ groups (n=16), with normal SD rats as the control group. The positive drugs and ZJJ were administered by gavage, and the rats in the control and model groups were given distilled water. After the treatment, blood glucose level was detected using test strips, and behavioral changes of the rats were assessed by forced swimming test and water maze test. ELISA was used to examine the serum level of leptin; The expressions of nestin and Brdu proteins in the dentate gyrus of the rats were detected using immunofluorescence assay, and the expressions of self-renewal marker proteins and Shh signaling proteins were detected using Western blotting.@*RESULTS@#The diabetic rats with depression showed significantly increased levels of blood glucose and leptin (P < 0.01) and prolonged immobility time in forced swimming test (P < 0.01) and increased stage climbing time with reduced stage seeking time and stage crossings in water maze test (P < 0.01). The expressions of nestin and Brdu in the dentate gyrus, the expressions of cyclin D1, SOX2, Shh, Ptch1, Smo in the hippocampus and the nuclear expression of Gli-1 were decreased (P < 0.01) while hippocampal Gli-3 expression was increased significantly (P < 0.01) in the rat models. Treatment of rat models with high-dose ZJJ significantly reduced the blood glucose (P < 0.01) and leptin level (P < 0.05) and improved their performance in behavioral tests (P < 0.01). The treatment also obviously increased the expressions of nestin, Brdu, cyclin D1, SOX2, Shh, Ptch1, and Smo and the nuclear expression of Gli-1 in the dentate gyrus (P < 0.01) and reduced hippocampal expression of Gli-3 (P < 0.05) in the rat models.@*CONCLUSION@#ZJJ can significantly improve the self-renewal ability of neural stem cells and activate Shh signaling in dentate gyrus of diabetic rats with depression.
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Animais , Ratos , Glicemia , Bromodesoxiuridina , Autorrenovação Celular , Ciclina D1 , Giro Denteado , Depressão , Diabetes Mellitus Experimental , Hipocampo , Leptina , Nestina , Ratos Sprague-DawleyRESUMO
Excitotoxicity mainly refers to the toxic effect of the excitatory neurotransmitter glutamate.Long-term activation of glutamate receptors will cause a series of neurotoxicity, eventually leading to the loss of neuronal function and cell death.Triggering excitotoxicity may involve changes in glutamate and calcium metabolism, dysfunction of glutamate transporter, N-methyl-D-aspartate receptor(NMDAR)and mitochondria, and production of ROS.Therefore, we here review the occurrence of these mechanisms and introduce the pathological mechanism of glutamate excitotoxicity in Alzheimer's disease(AD), Parkinson's disease(PD), depression and epilepsy.Finally, this review briefly describes the regulatory effects of broad-spectrum glutamic satellite modulators, marine compounds and Chinese herbal medicines on the glutamatergic system.
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Objective:To investigate the anti-anxious depression mechanism of Baihe Dihuangtang from the NOD-like receptor thermal protein domain 3 (NLRP3) inflammasome. Method:Fifty SD rats were randomly divided into normal group, model group, venlafaxine group (13.5 mg·kg<sup>-1</sup>), Baihe Dihuangtang high and low dose group (16,4 g·kg<sup>-1</sup>), with 10 rats in each group. Chronic restraint stress for 28 days (6 h) combined with subcutaneous injection of corticosterone (30 mg·kg<sup>-1</sup>) was used to establish induce an anxious depression model. From the 8th day of modeling, the rats in the normal group and the model group received distilled water, and those in groups with drug intervention were treated with corresponding drugs by gavage for 21 days. Elevated plus maze and open field test were used to evaluate the behavioral changes of rats. Enzyme- linked immunosorbent assay (ELISA) was used to detect serum and hippocampal interleukin-1<italic>β</italic> (IL-1<italic>β</italic>), interleukin-6 (IL-6) and interleukin-18 (IL-18) levels. Western blot were used to detect the relative expression of hippocampal NLRP3, apoptosis-associated speck-like protein containing a CARD (ASC), and Caspase-1. The pathological changes of the hippocampus were observed by hematoxylin-eosin(HE) staining, the average fluorescence intensity of NLRP3, ASC, and Caspase-1 was detected by immunofluorescence. The ultrastructure of neurons was observed under electron microscopy. Result:Compared with the normal group, the model group showed reduced total entries (TE), the ratio of open-arm entries (OE%), the ratio of open-arm times (OT%), and the autonomous activity score (<italic>P</italic><0.01), significant anxiety and depression-like behaviors, increased levels of IL-1<italic>β</italic>, IL-6, and IL-18 in the serum and hippocampus (<italic>P</italic><0.01), elevated protein expression of NLRP3, ASC, and Caspase-1 (<italic>P</italic><0.01), activated NLRP3 inflammasomes, and injured hippocampal neurons. Compared with the model group, the high-dose Baihe Dihuangtang group showed improved anxiety and depression-like behaviors (<italic>P</italic><0.01), and decreased levels of IL-1<italic>β</italic>, IL-6, and IL-18 in the serum and hippocampus (<italic>P</italic><0.05,<italic>P</italic><0.01), reduced protein expression of NLRP3, ASC, and Caspase-1 (<italic>P</italic><0.01), and alleviated hippocampal neuron damage. Conclusion:Baihe Dihuangtang can improve neuronal damage in anxious depression by inhibiting the excessive activation of NLRP3 inflammasomes.
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To explore the effect of Baihe Dihuang Decoction on the synaptic plasticity of hippocampal neurons in rats with anxious depression. Fifty SD rats were randomly divided into normal group, model group, venlafaxine group(6.75 mg·kg~(-1)), high-dose Baihe Dihuang Decoction group(8.64 g·kg~(-1)) and low-dose Baihe Dihuang Decoction group(4.32 g·kg~(-1)). Chronic restraint stress(6 h) combined with corticosterone(ih, 30 mg·kg~(-1)) was used to establish an anxious depression model, and 7 days after modeling, the administration started and continued for 21 days. The anxiety and depression-like behaviors of the rats were evaluated. Golgi-Cox staining and electron microscopy were used to observe the morphology and ultrastructural changes of synaptic dendrites. Immunofluorescence was used to detect the expression of hippocampal synaptic plasticity protein synapsin-1 and postsynaptic density protein 95(PSD-95). Western blot method was used to detect the expression of functional protein synaptophysin(SYP) and synaptic Ras GTPase activating protein(SynGap). The results showed that the rats in the model group had obvious anxiety and depression-like behaviors, the hip-pocampal dendritic spine density and branch length were reduced, the number of synapses was cut, and the internal structure was da-maged. The average fluorescence intensity of synapsin-1 and PSD-95 was significantly reduced and the expression of SYP and SynGap also decreased. High-dose Baihe Dihuang Decoction could significantly improve the anxiety and depression-like behaviors of model rats, relieve synaptic damage, and increase the expression of synapsin-1, PSD-95, SYP, and SynGap proteins. Therefore, we believe that Baihe Dihuang Decoction can improve anxiety and depression behaviors by regulating the synaptic plasticity of hippocampal neurons.
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Animais , Ratos , Depressão/tratamento farmacológico , Hipocampo , Plasticidade Neuronal , Ratos Sprague-Dawley , SinapsesRESUMO
Objective: The aim of this study was to review the published literature and investigate whether sex determining region Y-box 2 (SOX2) is a prognostic factor in head and neck squamous cell carcinoma (HNSCC) by conduct a meta-analysis. Materials and Methods: Trials were identified from the major electronic databases (MEDLINE, EMBASE, and Cochrane Library) using the key words “HNSCC” and “SOX2.” The overall survival (OS), disease-specific survival (DPS), and disease-free survival (DFS) were the primary outcome measures. Results: We identified 371 articles, 9 articles 11 studies with a total number of 1334 cases were eligible for inclusion of this meta-analysis. The results showed that OS (DPS) in low-expression group was higher than that in high-expression group. However, the difference between the two groups was not significant (hazard ratio [HR] = 1.30, 95% confidence interval [95% CI] = [0.88, 1.91]; P = 0.18), and there was great statistical heterogeneity (I2 = 66%, P = 0.002). After subgroup analysis, the HR for OS of the patients with reduced expression of SOX2 was 1.34 (95% CI = [1.04, 1.74], P = 0.03), and the heterogeneity became acceptable (I2 = 32%, P = 0.16). The HR for DFS of the patients with reduced expression of SOX2 was 1.39 (95% CI = [1.00, 1.93]; P = 0.05). Conclusion: The findings of this meta-analysis are indicative of that high SOX2 expression is a negative prognostic factor of HNSCC and exhibit both worse OS and DFS. However, the small sample size available for this systematic review limited the power of this quantitative meta-analysis. It may therefore be too early to place complete confidence in these results
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OBJECTIVE@#To study the effects of Zuogui Jiangtang Jieyu Formula (ZGJTJYF, the Chinese Medicine) on hippocampal neuron apoptosis in diabetes mellitus complicated with depression (DD).@*METHODS@#The primary cultured hippocampal neurons were treated with high glucose (150 mmol/L) and corticosterone (200 micromol/L) to establish the cell model of DD in vitro. The cultured hippocampal neurons were randomly divided into five groups: blank serum group, normal group, Zuogui Jiangtang Jieyu recipe drug-containing serum group, positive drug (metformin + fluoxetine) drug-containing serum group and model group (three compound holes in each group). The model group and the normal group were given the same amount of culture medium, and the other groups were given the corresponding serum with 10% volume fraction for 18 hours. Hoechst staining, high content cell imaging and RT-PCR were used to detect the apoptosis of hippocampal neurons and the expressions of apoptosis-related ETS-like 1 transcription factor(ELK-1), C-Jun N-terminal kinase(JNK) and c-Fos proteins and genes.@*RESULTS@#Compared with the blank group, the apoptotic number of hippocampal neurons in the model group was increased significantly, and the expression levels of ELK-1, JNK and c-Fos were increased significantly (P<0.05). Compared with the model group, the local bright spots of hippocampal neurons in the Zuogui Jiangtang Jieyu recipe-containing serum group and the positive drug-containing serum group were decreased significantly, and the number of apoptotic cells was decreased significantly. The expressions of JNK, c-fos protein and mRNA were down-regulated significantly (P< 0.05), and the neural network and dendritic junction were improved significantly.@*CONCLUSION@#Zuo Gui Jiang Tang Jie Yu Formula can reverse the expressions of ELK-1, JNK and c-Fos signals in hippocampal neurons under DD environment and play an anti-apoptotic effect.
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Animais , Ratos , Apoptose , Depressão , Tratamento Farmacológico , Complicações do Diabetes , Tratamento Farmacológico , Diabetes Mellitus , Medicamentos de Ervas Chinesas , Farmacologia , Hipocampo , MAP Quinase Quinase 4 , Neurônios , Proteínas Proto-Oncogênicas c-fos , Distribuição Aleatória , Proteínas Elk-1 do Domínio etsRESUMO
Objective To investigate the effects of Xiaoyao Kang'ai Jieyu Formula on mice with breast cancer related depression; To explore its mechanism. Methods BALB/c female mice were set as study objects. Subaxillary injection of inflammatory 4T1 cells and intraperitoneal injection of corticosterone were used to establish a model of breast cancer related depression. According to the consumption of sugar water, mice were randomly divided into blank group, model group, paclitaxel group, Xiaoyao Kang'ai Jieyu Formula group, chemotherapy+fluoxetine group, and chemotherapy + Xiaoyao Kang'ai Jieyu Formula group. After 21 days, sucrose preference test, open-field test, and novelty feeding test were performed to detect changes in the behavior of mice in each group. ELISA were used to detected the contents of corticotrophin releasing hormone (CRH), adrenocorticotropic hormone (ACTH), and corticosterone (CORT) in plasma, and the contents of 5-hydroxytryptamine (5-HT), dopamine (DA), norepinephrine (NE), tumor markers carbohydrate antigen CA153, CA125 and carcinoembryonic antigen (CEA) in serum. Results Compared with the blank group, the consumption of sugar, horizontal and vertical movements of mice in the model group significantly decreased (P<0.01, P<0.05); the latency of ingestion significantly increased (P<0.01, P<0.05); the levels of tumor markers CA153, CA125, CEA and some indexes of HPA axis significantly increased (P<0.01); the expressions of monoamine neurotransmitter NE, DA and 5-HT significantly decreased (P<0.01). Compared with the model group, sugar consumption and autonomic activity significantly increased in the chemotherapy + Xiaoyao Kang'ai Jieyu Formula group, and behavioral despair condition was improved (P<0.01, P<0.05); the content of tumor markers and some indexes related to HPA axis significantly decreased (P<0.01, P<0.05); the contents of 5-HT, DA and NE significantly increased (P<0.01, P<0.05). Conclusion The combination of Xiaoyao Kang'ai Jieyu Formula and paclitaxel can effectively relieve the depressive symptoms of breast cancer related depression.
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Aim To investigate the effects of chronic corticos-terone injection on anxiety and depression-like behavior of tree shrews, evaluate the predictability of drug and establish a novel animal model of anxious depression .Methods Twelve Chinese and Burma tree shrews were randomly divided into normal group, model group and venlafaxine group .The anxious depres-sion model of tree shrew was established by chronic corticoster-one injection ( ih, 27 mg· kg-1 , 21 d) .The venlafaxine group received intragastric administration (6 mg· kg-1).Autonomous activity score, sugar water preference test and Morris water maze test were used to evaluate the anxiety and depression-like behav-ior of tree shrews .The expressions of CRH , ACTH and COR in the tree shrew plasma were determined by Elisa kit .The con-tents of monoamine neurotransmitters of tree shrews in the hippo-campus , amygdala and prefrontal cortex were detected by HPLC-ECD.Results Compared with the normal group , the autono-mous activity score , sugar water partial eclipse degree and the learning and memory ability significantly decreased (P<0.01), while the contents of CRH , ACTH and COR significantly in-creased ( P<0.05) , and the contents of 5-HT, NE and DA in the hippocampus , amygdala and prefrontal cortex declined in the model group(P<0.05).In the venlafaxine group, the learning and memory abilities of the tree shrews were improved , the lev-els of CRH and COR in plasma were significantly decreased ( P<0.05), and the contents of 5-HT, NE and DA were increased (P<0.05).Conclusions The tree shrews of anxious depres-sion have obvious HPA axis hyperactivity and monoamine neuro-transmitter disorder , and venlafaxine can reverse this phenome-non, indicating that the tree shrews model of anxious depression has drug predictability , which is a kind of novel animal model of anxious depression closer to human in clinic .
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Objective To observe the effects of Zuogui Jiangtang Jieyu Prescription (ZGJTJYP) on pathological morphology of hippocampal neurons in rats of diabetes mellitus with depression (DD); To discuss its protective mechanism of action. Methods DD rat model was established by tail vein injection of STZ combined with chronic stress. Totally seventy-two SPF rats were randomly divided into normal group, model group, positive medicine group, ZGJTJYP low-, medium-, and high-dose groups, with 12 cases in each group, and were given corresponding medicine. After the last administration, blood glucose and behavioral changes were measured in each group. HE staining, Nissl staining, and Golgi staining were used to observe the changes of pathological morphology in rat hippocampus. The expression of Caspase-3 in hippocampus was detected by immunohistochemistry. Results Compared with the normal group, blood glucose level was significantly increased in the model group; the number of neurons in the hippocampus decreased in the model group; the apoptosis increased in the model group; the neuronal soma showed deformation and reduced dendritic spines and other pathological damages in the model group. After intervention of ZGJTJYP, hyperglycemia and depression-like status of the model rats were relieved; the number of hippocampal neurons increased significantly; neuronal morphology basically returned to normal. The expression of Caspase-3 in ZGJTJYP high-and medium-dose groups was significantly lower than that in model group. Conclusion ZGJTJYP can significantly improved blood glucose and learning and memory abilities in DD rats, which may be related to slowing hippocampal injury and apoptosis, and restoring neuronal quantity and morphology.
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Objective To screen the optimized Buyang Huanwu Decoction (BYHWD);To verify it. Methods H2O2 was used to induce PC12 cell oxidative stress models. MTT method was used to determine the prevention effects of BYHWD at different concentrations (0.1, 0.2, 0.5, 1.0, 2.0, 3.5 mg/mL) on in vitro oxidative stress cell models to define the optimized concentration. Orthogonal design was used to divide BYHWD single medicine into decomposed BYHWD groups, control group (only with DMEM), normal group (without H2O2 and medicine processing), and model group, to investigate the protective effects on PC12 cells. Optimized BYHWD was screened to decide the compatibility ratio of each medicine. MTT was used to detect the cell survival rate in each group. Middle cerebral artery occlusion was used to replicate MACO rat models. SD rats were randomly divided into sham-operation group, model group, BYHWD group and optimized BYHWD high-, medium-and low-dose groups. Each medication group was given relevant medicine for gavage. The screened results were verified. Results Compared with other decomposed BYHWD groups, the protective effects of the compatibility of Astragali Radix+Chuanxiong Rhizoma+Pheretima on PC12 cells was the best (P<0.05), which was nearly equaled to BYHWD. Compared with the model group, BYHWD and the optimized one could evidently reduce cerebral cortex infarction area and improve the impaired brain edema (P<0.05), and the medium-dose group was the best. Conclusion The optimized BYHWD ratio is:Astragali Radix:Chuanxiong Rhizoma:Pheretima=10:3:1.
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Objective To compare the biological characteristics of several different anxiety rat models established by different methods of stress at different time points and provide experimental basis for the most appropriate modeling methods .Methods 60 rats were randomly divided into normal , empty bottle stress , chronic emotional stress ( CES ) group, restraint stress for 3h, 6h, and modeling respectively .In the experimental 7 d, 14 d, 21 d, elevated plus maze and fear condition system was used to test anxiety-like behavior in rats , open field test to study anxiety or depression-like behavior , forced swimming test was used to detect depression-like behavior in rats , and using the Elisa test kit to detect the contents of 5-HT, DA in the hippocampus in rats .Results Anxiety-like behavioral test results showed that rats in empty bottle stress, CES, 6 h restraint stress group started to have anxiety-like behavior since 14 d, then anxiety-like behavior was becoming increasingly apparent .Forced swimming test results showed that immobility time in 6 h restraint rats was significantly increased in the first 7 d(P <0.05).Meanwhile, compared with control group, hippocampal 5-HT, DA contents in empty bottle stress and CES rats increased significantly since 14 d.Conclusions Among several stress methods established anxiety model , anxiety-like behavior in 3 h restraint stress was not obvious; 6 h restraint stress exhibited a depression-like behavior in the forced swimming test might be due to prolonged stress .Empty bottle stress and CES can successfully establish the anxiety rat model , and the anxiety behavior of the rats have some differences . Corresponding model methods can be selected according to different experimental purposes .
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Objective To study the content of monoamine neurotransmitters and neurotrophic factor in the hippocampus, amygdala and prefrontal cortex in anxious depression rats, and explore the possible pathogenesis.Methods 60 SD rats were randomly divided into normal group, vehicle group, anxiety group, depression group, and anxious depression group, 12 rats in each group.Chronic restraint stress combined with corticosterone injection was used to establish anxiety and depression model, the modeling time was 21 d.After modeling, elevated plus maze test, open field test, and forced swimming test were used to evaluate the anxiety and depression-like behavior, HPLC-ECD was used to detect the content of 5-HT, NE, and DA in the hippocampus, amygdala, and prefrontal cortex of rats.Western-blotting was used to detect the expression of BDNF and NT-3 in rats.Results Rats in anxious depression model group were comparable to the anxiety group in time and frequency entering open arm time, and number of locomotor activity in open field, and it had a significant difference when compared with the control and depression groups (P<0.01 or P<0.05).Immobile time in anxious depression model rats was increased significantly when compared with the control and anxiety groups (P<0.01).Meanwhile, compared with the control group, 5-HT in hippocampus and 5-HT, NE in amygdala or prefrontal cortex were significantly decreased in the depressive rats with anxiety (P<0.01 or P<0.05).Moreover, the content of BDNF and NT-3 was significantly decreased in each brain regions compared with the control group (P<0.01 or P<0.05), and BDNF levels were obviously decreased compared with the anxiety group (P<0.05).Conclusions Rats of anxious depression have significant anxiety and depression-like behaviors.Its mechanism may be associated with the down-regulation of monoamine neurotransmitters and neurotrophic factors BDNF and NT-3 in hippocampus, amygdala, and prefrontal cortex region.
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Objective To investigate the effects of dizocilpine(MK801) on depressive-like behaviors and damaged hippocampus in rats with diabetes-related depression.MethodsThe animal models of diabetes-related depression were established and they were randomly divided into two groups based on random number table: model group and MK801 group,while 6 rats were included in each group.And another six health rats were regarded as control group.The Open-field test was used to detect the activities.The damage of hippocampus was valued by HE staining,Nissl staining,and Tunel staining.The protein expressions of Bax,Bcl-2 in hippocampus were detected by Western blot.ResultsThe number of activities was significant decreased in Open-field test in model group when compared with control.Hippocampal neurons vacuoles,Nissl bodies were decreased and apoptotic cells were increased in hippocampus in model group as well.Furthermore,the expression of Bax was significant up-regulated(94.57±7.97,P<0.01),while the Bcl-2 was declined(24.65±5.26,P<0.01).Compared with the model group,the animals in MK801 group exhibited increased activities(12.50±4.42,P<0.01),which accompany with an increased Nissl body(133.55±16.74,P<0.01) and a decreased apoptosis(22.50±6.35,P<0.01).Moreover,the expression of Bax was decreased and the Bcl-2 was increased in MK801 group when they were contrasted to model(33.00±4.57,P<0.01).Conclusion MK801 is a significant element to regulate the expression of apoptosis protein including Bax,Bcl-2,and to protecte the hippocampal neuron in rats with diabetes-related depression effectively.
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Objective To observe the effects of Baishile Capsules on the hippocampal PI3K signaling pathway in chronic mild unpredictable stress (CUMS) rats; To discuss its mechanism of action for anti-depression. Methods SD rats were randomly divided into 6 groups, control group, model group, fluoxetine group, Baishile Capsules high-, medium- and low-dose groups, with 10 rats in each group. The cums depression model was established, and gavage for medication was conducted at the same time for 21 days in a row. The behavioral changes of rats in each group were detected by the novel feeding experiment and Open-field experiment; monoamine neurotransmitter in serum were detected by ELISA; the expressions of PI3K, AKT and SGK1 in rat hippocampus were detected by immunofluorescence and Western blot test. Results Compared with the control group, feeding latency of rats in model group was significantly prolonged (P<0.01), horizontal and vertical activities were significantly reduced (P<0.01); the content of serum monoamine neurotransmitter decreased (P<0.01); the expressions of PI3K and AKT in hippocampus decreased, while the expression of SGK1 increased (P<0.01, P<0.05). Compared with the model group, Baishile Capsule high- and medium-dose groups can significantly shorten the incubation period of feeding rats (P<0.05), and increase the number of horizontal and vertical activities (P<0.01); the 5-HT and NE levels in serum were significantly elevated (P<0.05, P<0.01); the expressions of PI3K, AKT in hippocampal increased; the expression of SGK1 decreased (P<0.05, P<0.01). Conclusion Baishile Capsules can alleviate the depression like behavior in rat models, and regulate key factors of hippocampal PI3K signaling pathway, so as to exert antidepressant effects.
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Objective To investigate the effects of Zuogui Jiangtang Jieyu Prescription on neurotrophic effects of astrocytes in diabetes mellitus rats with depression. Methods The diabetes mellitus with depression rat models were established by composite method, and then were randomly divided into 5 groups: model group, positive group, Zuogui Jiangtang Jieyu Prescription high-, medium-, low-dose groups, with 12 rats in each group. 12 normal rats were set as control group. Each administration group was given relevenat medicine for gavage for continuous 4 weeks. Open-field test was used to evaluate the depression-like behavior. The expression of GFAP in astrocyte and MAP2 in neuron were tested by immunohistochemistry. The expression of protein and mRNA of BDNF, GDNF, and NGF were tested by Western blot and RT-PCR. Results Compared with the control group, the activities of rats in model group were significantly reduced. The expression of GFAP increased, while the expressions of MAP2, BDNF, GDNF and NGF decreased. Compared with the model group, the depression-like behavior of rats in model group were significantly improved. The expression of GFAP decreased, while the expressions of MAP2, BDNF, GDNF and NGF increased, and GFAP decrseaed significantly. Conclusion The secretion function of astrocyte can be improved by Zuogui Jiangtang Jieyu Prescription. Its anti-depression and neuron-protection function might be correlated with the enhancement of neurotrophic effects of astrocytes.
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Objective To study the changes of behavior and depression-like classic indicators after hippocampal microinjection of K252a,and to establish a new animal model of depression.Methods SD rats were randomly divided into five groups,namely the control group,sham group,chronic stress depression model group,hippocampal of K252a microinjection group,and hippocampal microinjection K252a plus chronic stress group.Open field experiments,sucrose consumption test,and Morris water maze behavioral assay were used to assess the behavioral changes in the rats.ELISA was used to detect the plasma monoamine neurotransmitter,radioimmunoassay was used to determine the plasma CRH,ACTH,CORT contents,and western-blotting was performed to observe the protein expression of BDNF,CREB,ERK1/2,and BCL-2 in the hippocampus.Results Compared with the control group,the amount of activity,sugar consumption,learning and memory abilities were decreased(P<0.05 or P<0.01),also the serum monoamine neurotransmitters were decreased (P<0.01),HPA axis function was improved (P<0.01),and the expression of BDNF,CREB,ERK1/2,BCL-2 decreased in the CUMS group(P<0.05 or P<0.01),but there was no significant difference in the DMSO group.Compared with the DMSO group,the activity,consumption of sucrose,learning and memory ability were significantly decreased(P<0.05 or P<0.01),while the HPA axis function was increased (P<0.05 or P<0.01),the serum monoamine neurotransmitters decreased(P<0.05 or P<0.01),and the BDNF,CREB,ERK1/2,BCL-2 expressions in the hypocampus were significantly decreased(P<0.05 or P<0.01) in the K252a group and K252a + CUMS group.Compared with the CUMS group,the K252a group and K252a + CUMS group did not show significant changes in these parameters.Compared with the K252a group,these indicators were not significantly changed in the K252a + CUMS group.Conclusions The results of behavior,hematology,and molecular biology analysis show that this model has a great similarity to the classical model of CUMS in surface validity,construct validity,and functional validity.It may provide an alternative investigative technology platform for basic research and antidepressant drug screening.
RESUMO
<p><b>OBJECTIVE</b>To investigate the effect of air pollution on respiratory health in school-aged children in the main urban area of Chongqing, China.</p><p><b>METHODS</b>The main urban area of Chongqing was divided into polluted area and clean area according to the air pollution data shown on the Environmental Protection Agency Website of Chongqing between 2010 and 2015. A cluster sampling method was used to select 695 third- or fourth-grade children from 2 primary schools in the clean or polluted area as study subjects, with 313 children from the clean area and 382 children from the polluted area. Pulmonary function was examined for all children and a standard American epidemiological questionnaire (ATS-DLD-78-C) was used to investigate the prevalence of respiratory diseases and symptoms.</p><p><b>RESULTS</b>Compared with the clean area, the polluted area had significantly higher concentrations of inhalable particles (PM), fine particulate matter (PM), and nitric oxide (NO) (P<0.05). The multivariate logistic regression analysis was performed after adjustment for confounding factors, and the results showed that compared with those in the clean area, the children in the polluted area had significantly higher risks of cough (OR=1.644), cough during cold (OR=1.596), expectoration during cold (OR=2.196), persistent expectoration (OR=1.802), and wheezing (OR=2.415). The boys and girls in the clean area had significantly higher forced vital capacity and forced expiratory volume in one second than those in the polluted area (P<0.05).</p><p><b>CONCLUSIONS</b>Air pollution in the main urban area of Chongqing is associated with the increased prevalence of respiratory symptoms in school-aged children and has certain effect on children's pulmonary function.</p>