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A novel dual serotonin transporter and M-channel inhibitor D01 for antidepression and cognitive improvement

Acta Pharmaceutica Sinica B 2024年第3期14卷 1457-1466页

作者： yaqin wei Xiangqing Xu Qiang Guo Song Zhao Yinli Qiu Dongli Wang Wenwen Yu Yani Liu Kewei Wang School of Pharmacy Xuzhou Medical UniversityXuzhou 221004China Institute of Pharmaceutical Research Jiangsu Nhwa Pharmaceutical Co.Ltd.&Jiangsu Key Laboratory of Central Nervous System Drug Research and DevelopmentXuzhou 221116China Department of Pharmacology School of PharmacyQingdao University Medical CollegeQingdao 266073China Institute of Innovative Drug Qingdao UniversityQingdao 266021China Center for Brain Science and Brain-Inspired Intelligence Guangdong-Hong Kong-Macao Greater Bay AreaGuangzhou 510515China

Cognitive dysfunction is a core symptom common in psychiatric disorders including depression that is primarily managed by antidepressants lacking efficacy in improving *** this study,we report a novel dual serotonin transporter and voltage-gated potassium Kv7/KCNQ/M-channel inhibitor D01(a 2-methyl-3-aryloxy-3-heteroarylpropylamines derivative)that exhibits both anti-depression effects and improvements in cognition.D01 inhibits serotonin transporters(K_(i)=30.1±6.9 nmol/L)and M channels(IC_(50)=10.1±2.4μmol/L).D01 also reduces the immobility duration in the mouse FST and TST assays in a dose-dependent manner without a stimulatory effect on *** administrations of D01(20 and 40 mg/kg)can significantly shorten the immobility time in a mouse model of chronic restraint stress(CRS)-induced depression-like ***,D01 dose-dependently improves the cognitive deficit induced by CRS in Morris water maze test and increases the exploration time with novel objects in normal or scopolamine-induced cognitive deficits in mice,but not ***,D01 reverses the long-term potentiation(LTP)inhibition induced by *** together,our findings demonstrate that D01,a dual-target serotonin reuptake and M channel inhibitor,is highly effective in the treatment-resistant depression and cognitive deficits,thus holding potential for development as therapy of depression with cognitive deficits.

关键词： SERT 5-HT Kv7/KCNQ/M current D01 Depression Cognition

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Neural stem cell-derived exosomes regulate cell proliferation,migration,and cell death of brain microvascular endothelial cells via the miR-9/Hes1 axis under hypoxia

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Animal Models and Experimental Medicine 2024年第1期7卷 24-35页

作者： Xiaojun Deng Xiaoyi Hu Shang Wang Hui Zhao yaqin wei Jiaqi Fu Wenhui Wu Jinming Liu Caicai Zhang Lili Wang Ping Yuan Department of Critical Care Medicine Shanghai Sixth People's HospitalShanghai Jiao Tong UniversityShanghaiChina Department of Cardio-Pulmonary Circulation Shanghai Pulmonary HospitalSchool of MedicineTongji UniversityShanghaiChina Institute of Bismuth Science University of Shanghai for Science and TechnologyShanghaiChina Department of Physiology Hainan Medical University HaikouHainanChina Department of Clinical Medical Laboratory Center Hangzhou Red Cross HospitalZhejiangChina

Background:Our previous study found that mouse embryonic neural stem cell(NSC)-derived exosomes(EXOs)regulated NSC differentiation via the miR-9/Hes1 ***,the effects of EXOs on brain microvascular endothelial cell(BMEC)dysfunction via the miR-9/Hes1 axis remain ***,the current study aimed to determine the effects of EXOs on BMEC proliferation,migration,and death via the miR-9/Hes1 ***:Immunofluorescence,quantitative real-time polymerase chain reaction,cell counting kit-8 assay,wound healing assay,calcein-acetoxymethyl/propidium iodide staining,and hematoxylin and eosin staining were used to determine the role and mechanism of EXOs on ***:EXOs promoted BMEC proliferation and migration and reduced cell death under hypoxic *** overexpression of miR-9 promoted BMEC prolifera-tion and migration and reduced cell death under hypoxic ***,miR-9 downregulation inhibited BMEC proliferation and migration and also promoted cell ***1 silencing ameliorated the effect of amtagomiR-9 on BMEC proliferation and migration and cell *** structures were observed in the regions of the hippocampus and cortex in hypoxia-induced ***,EXO treatment improved cerebrovascular ***:NSC-derived EXOs can promote BMEC proliferation and migra-tion and reduce cell death via the miR-9/Hes1 axis under hypoxic ***,EXO therapeutic strategies could be considered for hypoxia-induced vascular injury.

关键词： brain microvascular endothelial cells exosomes Hes1 miR-9 neural stem cells

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CircPMS1 promotes proliferation of pulmonary artery smooth muscle cells,pulmonary microvascular endothelial cells,and pericytes under hypoxia

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Animal Models and Experimental Medicine 2024年第3期7卷 310-323页

作者： Xiaoyi Hu Shang Wang Hui Zhao yaqin wei Ruowang Duan Rong Jiang Wenhui Wu Qinhua Zhao Sugang Gong Lan Wang Jinming Liu Ping Yuan Department of Cardio-Pulmonary Circulation Shanghai Pulmonary HospitalSchool of MedicineTongji UniversityShanghaiChina Institute of Bismuth Science University of Shanghai for Science and TechnologyShanghaiChina Department of Geriatrics Shanghai Institute of GeriatricsHuadong HospitalFudan UniversityShanghaiChina Department of Anesthesiology Shanghai Pulmonary HospitalSchool of MedicineTongji UniversityShanghaiChina

Background:Circular RNAs(circRNAs)have been recognized as significant regulators of pulmonary hypertension(PH);however,the differential expression and function of circRNAs in different vascular cells under hypoxia remain ***,we identified co-differentially expressed circRNAs and determined their putative roles in the proliferation of pulmonary artery smooth muscle cells(PASMCs),pulmonary microvascular endothelial cells(PMECs),and pericytes(PCs)under ***:Whole transcriptome sequencing was performed to analyze the differential expression of circRNAs in three different vascular cell *** analysis was used to predict their putative biological *** real-time polymerase chain reaction,Cell Counting Kit-8,and EdU Cell Proliferation assays were carried out to determine the role of circular postmeiotic segregation 1(circPMS1)as well as its potential sponge mechanism in PASMCs,PMECs,and ***:PASMCs,PMECs,and PCs exhibited 16,99,and 31 differentially expressed circRNAs under hypoxia,***1 was upregulated in PASMCs,PMECs,and PCs under hypoxia and enhanced the proliferation of vascular ***1may upregulate DEP domain containing 1(DEPDC1)and RNA polymerase II subunit D expression by targeting microRNA-432-5p(miR-432-5p)in PASMCs,upregulate MAX interactor 1(MXI1)expression by targeting miR-433-3p in PMECs,and upregulate zinc finger AN1-type containing 5(ZFAND5)expression by targeting miR-3613-5p in ***:Our results suggest that circPMS1 promotes cell proliferation through the miR-432-5p/DEPDC1 or miR-432-5p/POL2D axis in PASMCs,through the miR-433-3p/MXI1 axis in PMECs,and through the miR-3613-5p/ZFAND5 axis in PCs,which provides putative targets for the early diagnosis and treatment of PH.

关键词： circular postmeiotic segregation 1 circular RNAs hypoxia pulmonary hypertension vascular cells

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犏牛瘤胃厌氧真菌和甲烷菌共培养物发酵液预处理玉米秸秆对其黄贮品质的功效研究

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中国饲料 2024年第10期 5-10页

作者：方彦昊王霄霄魏亚琴甘肃省科学院生物研究所厌氧微生物中心甘肃兰州730030 兰州理工大学生命科学与工程学院甘肃兰州730050

厌氧真菌能降解木质纤维素,一些甲烷菌可以增强厌氧真菌的降解能力。将犏牛瘤胃厌氧真菌和甲烷菌共培养物(***+***)Cattle-YakTZ1降解秸秆产生的发酵液预处理玉米秸秆48 h后进行黄贮,以市售木聚糖酶做对照组,空白组不进行预处理。结果表... 详细信息

厌氧真菌能降解木质纤维素,一些甲烷菌可以增强厌氧真菌的降解能力。将犏牛瘤胃厌氧真菌和甲烷菌共培养物(***+***)Cattle-YakTZ1降解秸秆产生的发酵液预处理玉米秸秆48 h后进行黄贮,以市售木聚糖酶做对照组,空白组不进行预处理。结果表明,空白组在发酵45 d后感官品质极差,DM流失率较高,ADF和NDF降解效果不明显,pH值为6~7,已严重发生霉变;对照组与试验组在发酵过程中DM得到有效保存,NDF、ADF含量显著降低,试验组的乳酸含量显著高于对照组,丁酸检出量较低,CP含量显著高于空白组。(***+***)Cattle-YakTZ1发酵液预处理玉米秸秆后进行黄贮显著提升了黄贮感官品质、发酵特性营养成分,具有独特的应用价值。

关键词：犏牛厌氧真菌共培养物黄贮发酵品质

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温针灸夹脊穴在寒湿痹阻型椎动脉型颈椎病中的应用效果及对颈椎功能的影响

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中国医药指南 2024年第9期22卷 141-144页

作者：彭斌魏雅琴林福清吴惠玲福建省古田县医院宁德352200

目的探讨针对寒湿痹阻型椎动脉型颈椎病患者通过温针灸夹脊穴治疗的疗效以及给患者颈椎功能恢复产生的影响。方法选择我院2022年1月至2022年12月收治的120例寒湿痹阻型椎动脉型颈椎病患者,以患者治疗方案的不同将其分为观察组与对照组... 详细信息

目的探讨针对寒湿痹阻型椎动脉型颈椎病患者通过温针灸夹脊穴治疗的疗效以及给患者颈椎功能恢复产生的影响。方法选择我院2022年1月至2022年12月收治的120例寒湿痹阻型椎动脉型颈椎病患者,以患者治疗方案的不同将其分为观察组与对照组各60例。对照组患者以常规牵引、普通针刺等治疗方法为主,观察组患者加以温针灸夹脊穴治疗,比较两组患者临床治疗效果、颈椎功能、中医证候积分、血流动力学指标改善效果。结果治疗后,观察组临床疗效(96.67%)高于对照组(71.67%)(P0.05);治疗后与治疗前比,两组中医证候积分和颈椎功能障碍指数均降低,且观察组低于对照组(P<0.05);治疗后,观察组的血流动力学指标改善效果高于对照组(P<0.05)。结论采用温针灸夹脊穴治疗椎动脉型颈椎病患者,可改善患者颈椎功能障碍,提高疗效,降低中医证候积分,提高患者血流动力学指标。

关键词：温针灸夹脊穴椎动脉型颈椎病寒湿痹阻型颈椎功能

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Improving hydrogen storage thermodynamics and kinetics of Ce-Mg-Ni-based alloy by mechanical milling with TiF_(3)

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Journal of Magnesium and Alloys 2024年第4期12卷 1593-1607页

作者： Hongwei Shang wei Zhang Xin wei yaqin Li Zeming Yuan Jun Li Yanghuan Zhang School of Mechanical and Electrical Engineering Chuzhou UniversityChuzhou 239000China Department of Functional Material Research Central Iron and Steel Research InstituteNo.76 Xueyuannan RoadHaidian DistrictBeijing 100081China Key Laboratory of Integrated Exploitation of Bayan-Obo Multi-Metal Resources Inner Mongolia University of Science and TechnologyBaotou 014010China China Rare Earth New Material(weishan)Co. Ltd.Jining 277600China

Mg-based hydrides are too stable and the kinetics of hydrogen absorption and desorption is not *** efficient way to improve these shortcomings is to employ reactive ball milling to synthesize the nanocomposite materials of Mg and *** this experiment,TiF_(3)was selected as an additive,and the mechanical milling method was employed to prepare the experimental *** alloys used in this experiment were the as-cast Ce_(5)Mg_(85)Ni_(10),as-milled Ce_(5)Mg_(85)Ni_(10)and Ce_(5)Mg_(85)Ni_(10)+3 wt.%*** phase transformation,structural evolution,isothermal and non-isothermal hydrogenation and dehydrogenation performances of the alloys were inspected by XRD,SEM,TEM,Sievert apparatus,DSC and *** revealed that nanocrystalline appeared in the as-milled *** with the as-cast alloy,ball milling made the particle dimension and grain size decrease dramatically and the defect density increase *** addition of TiF_(3)made the surface of ball milling alloy particles markedly coarser and more *** milling and adding TiF_(3)distinctly improved the activation and kinetics of the ***,ball milling along with TiF_(3)can decrease the onset dehydrogenation temperature of Mg-based hydrides and slightly ameliorate their thermodynamics.

关键词： Mg-based hydrides TiF_(3) Ball milling Thermodynamics Kinetics

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Design and construction of size-controlled CoO/CS catalysts for Fischer–Tropsch synthesis

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Nano Research 2024年第4期17卷 2520-2527页

作者： wei Sun Ting Kuang Guiyou wei Yue Li yaqin Liu Shuai Lyu Yuhua Zhang Jinlin Li Li Wang Key Laboratory of Catalysis and Energy Materials Chemistry of Ministry of Education&Hubei Key Laboratory of Catalysis and Materials Science South-Central Minzu UniversityWuhan 430074China Hubei Key Laboratory of Biomass Fibers and Eco-dyeing&Finishing College of Chemistry and Chemical EngineeringWuhan Textile UniversityWuhan 430200China

The use of supported Co-based catalysts is widespread in various catalytic reactions due to their unique *** structural sensitivity of these catalysts is closely linked to their particle size and crystal ***,comprehending the structure–activity relationship requires the development of well-defined Co-based ***,we employed a colloidal wet chemical process and a heterogeneous nucleation method to prepare well-defined Co-based catalysts supported by inert carbon *** nanospheres’surface possesses abundant functional groups that efficiently capture metal complexes and facilitate the nucleation and growth of CoO *** adjusting the Co source concentration,solvent molar ratio,and nucleation growth kinetics,we successfully prepared CoO/carbon sphere(CS)catalysts with different particle sizes and crystal *** influence of metallic face-centered cubic(fcc)-Co^(0) particle size in the range of 6.6–17.6 nm on the performance of Fischer–Tropsch synthesis(FTS)using well-defined CoO/CS catalysts has been *** result demonstrated that the turnover frequency(TOF)remained constant for CoO/CS catalysts with metallic fcc-Co^(0) particle size larger than 7.7 ***,both the selectivity and the activity changed for CoO/CS catalysts with smaller particles(<7.7 nm).Significantly,when metallic fcc-Co^(0) particle size was reduced from 17.6 to 7.7 nm,the cobalt time yield increased to 6.7μmolCO·gCo^(-1)·s^(-1),indicating improved catalytic *** the same time,the CH_(4) selectivity decreased to 4.9%,suggesting a higher preference for hydrocarbon *** findings demonstrate the importance of particle size in Co catalyzed Fischer–Tropsch *** use of well-defined CoO/CS catalysts offers valuable insights into the structure–activity relationship,leading to a better understanding of Co catalyzed Fischer–Tropsch synthesis.

关键词： Fischer–Tropsch synthesis(FTS) cobalt size effects phase effects carbon nanospheres

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Coexisting fast–slow dendritic traveling waves in a 3D-array electric field coupled neuronal network

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Chinese Physics B 2024年第6期33卷 614-626页

作者：魏熙乐任泽宇卢梅丽樊亚琴常思远 The Tianjin Key Laboratory of Process Measurement and Control School of Electrical and Information EngineeringTianjin UniversityTianjin 300072China School of Information Technology Engineering Tianjin University of Technology and EducationTianjin 300074China

Coexistence of fast and slow traveling waves without synaptic transmission has been found in hhhippocampal tissues,which is closely related to both normal brain activity and abnormal neural activity such as epileptic discharge. However, the propagation mechanism behind this coexistence phenomenon remains unclear. In this paper, a three-dimensional electric field coupled hippocampal neural network is established to investigate generation of coexisting spontaneous fast and slow traveling waves. This model captures two types of dendritic traveling waves propagating in both transverse and longitude directions: the N-methyl-D-aspartate(NMDA)-dependent wave with a speed of about 0.1 m/s and the Ca-dependent wave with a speed of about 0.009 m/s. These traveling waves are synaptic-independent and could be conducted only by the electric fields generated by neighboring neurons, which are basically consistent with the in vitro data measured experiments. It is also found that the slow Ca wave could trigger generation of fast NMDA waves in the propagation path of slow waves whereas fast NMDA waves cannot affect the propagation of slow Ca waves. These results suggest that dendritic Ca waves could acted as the source of the coexistence fast and slow waves. Furthermore, we also confirm the impact of cellular spacing heterogeneity on the onset of coexisting fast and slow waves. The local region with decreasing distances among neighbor neurons is more liable to promote the onset of spontaneous slow waves which, as sources, excite propagation of fast waves. These modeling studies provide possible biophysical mechanisms underlying the neural dynamics of spontaneous traveling waves in brain tissues.

关键词： hippocampal network epileptiform dendritic oscillation traveling wave electric field coupling

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嗜酸性粒细胞在肺癌中的研究进展

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中华预防医学杂志 2023年第11期57卷 1895-1900页

作者：魏亚勤吕丽华李明蚌埠医学院检验医学院蚌埠233030 中国科学技术大学附属第一医院检验科中国科学技术大学生命科学与医学部合肥230032

嗜酸性粒细胞是人体中一种含有嗜酸性颗粒的细胞,主要在过敏性疾病(如哮喘、蠕虫感染等)中发挥关键作用。越来越多的研究证实嗜酸性粒细胞可以浸润多种肿瘤组织,并在特定情况下合成和分泌大量生物活性物质,如细胞毒性阳离子蛋白、细胞... 详细信息

嗜酸性粒细胞是人体中一种含有嗜酸性颗粒的细胞,主要在过敏性疾病(如哮喘、蠕虫感染等)中发挥关键作用。越来越多的研究证实嗜酸性粒细胞可以浸润多种肿瘤组织,并在特定情况下合成和分泌大量生物活性物质,如细胞毒性阳离子蛋白、细胞因子、生长因子、趋化因子、酶等,这些物质可能影响血管生成、基质重塑或改变肿瘤微环境,进而影响肿瘤发生发展。本文对嗜酸性粒细胞在肺癌中的研究新进展进行阐述。

关键词：嗜酸性粒细胞肺癌肿瘤微环境免疫治疗生物标志物

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齐洛那平临床前体外及体内抗精神分裂症药效的初步研究

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中华精神科杂志 2022年第6期55卷 451-458页

作者：魏雅芹徐祥清邱印利于民权徐州医科大学药学院徐州221004 江苏恩华药业股份有限公司江苏省中枢神经药物研究重点实验室徐州221000

目的考察齐洛那平对不同精神分裂症动物模型的药效及其对多巴胺D_(1)、D_(2)等受体的体外亲和力。方法纳入雄性SPF级ICR小鼠324只,雄性SPF级Wistar大鼠72只及SPF级SD大鼠雌雄各10只为研究对象。(1)取100只ICR小鼠分为10组:空白组(溶媒+... 详细信息

目的考察齐洛那平对不同精神分裂症动物模型的药效及其对多巴胺D_(1)、D_(2)等受体的体外亲和力。方法纳入雄性SPF级ICR小鼠324只,雄性SPF级Wistar大鼠72只及SPF级SD大鼠雌雄各10只为研究对象。(1)取100只ICR小鼠分为10组:空白组(溶媒+生理盐水,简称Veh+NS),模型组(Veh+APO 1 mg/kg),利培酮(0.03、0.10、0.30、1.00 mg/kg,灌胃)+APO组,齐洛那平(0.3、1.0、3.0、10.0 mg/kg,灌胃)+APO组;每组10只,观察齐洛那平对小鼠攀爬行为的影响。(2)取84只ICR小鼠分为10组:空白组(Veh+NS),模型组(Veh+MK-8010.3 mg/kg),利培酮(0.01、0.03、0.10、0.30 mg/kg,灌胃)+MK-801组,齐洛那平(0.3、1.0、3.0、10.0 mg/kg,灌胃)+MK-801组;每组8~10只,观察齐洛那平对MK-801诱导小鼠高活动行为的影响。(3)取70只ICR小鼠分为7组:空白组(Veh),利培酮0.3、1.0及3.0 mg/kg组(灌胃),齐洛那平15、27及45 mg/kg组(灌胃),每组10只,观察小鼠在给药后30、60及90 min时保持僵住不动的时间。(4)取72只Wistar大鼠进行条件回避反应训练,将训练成功的大鼠分为7组:空白组(Veh),齐洛那平20、40及60 mg/kg组,利培酮0.2、0.4及0.8 mg/kg组,每组5~6只,考察齐洛那平对大鼠回避反应次数的影响。(5)取70只ICR小鼠,颈部皮下注射给予PCP(5 mg/kg)造模后,将小鼠分为空白组(Veh+NS),模型组(Veh+PCP),利培酮0.05 mg/kg+PCP组,齐洛那平(0.5、1.0、2.0 mg/kg)+PCP组,每组10~12只,考察齐洛那平对PCP诱导小鼠新物体识别障碍的影响。(6)将20只SD大鼠(雌雄各半)断头取脑,并制备5-HT_(2A)及5-HT_(2C)受体膜,取表达CHO-D_(1)、D_(2)及5-HT_(6)受体的细胞株制备D_(1)、D_(2)及5-HT_(6)受体膜,通过放射性配体受体结合的实验方法,考察齐洛那平对D_(1)、D_(2)、5-HT_(2A)、5-HT_(6)及5-HT_(2C)的亲和力。组间计量资料比较采用单因素方差分析,计数资料采用非参数U检验。结果(1)与模型组比较,齐洛那平剂量3.0及10.0 mg/kg可显著抑制APO诱导的小鼠攀爬行为(Z=-3.43、-4.07,均P<0.01),ED_(50)为4.31 mg/kg。利培酮剂量在0.10、0.30及1.00 mg/kg可显著抑制小鼠攀爬行为(Z=-1.83、-2.48、-4.26,P<0.05或P<0.01),ED_(50)为0.19 mg/kg。(2)与模型组比较,齐洛那平剂量3.0及10.0 mg/kg可显著抑制MK-801诱导的小鼠高活动行为(t=-7.18、3.90,均P<0.01),ED_(50)为2.63 mg/kg。利培酮0.01、0.03、0.10及0.30 mg/kg均显著抑制小鼠高活动行为(t=-3.02、4.98、-6.08、7.10,均P<0.01),ED_(50)为0.011 mg/kg。(3)齐洛那平及利培酮均可诱发小鼠产生僵住症,其ED_(50)分别为35.36 mg/kg及1.25 mg/kg。(4)齐洛那平以及利培酮均能剂量依赖性抑制大鼠的回避反应次数,与空白组比较,齐洛那平剂量在40及60 mg/kg时可显著性抑制大鼠条件回避反应次数(t=11.84、13.07,均P<0.01),ED_(50)为34.36 mg/kg;利培酮0.8 mg/kg可显著抑制大鼠条件回避反应次数(t=13.50,P<0.01),ED_(50)为0.60 mg/kg。(5)与模型组比较,齐洛那平0.5及1.0 mg/kg给药时能显著改善PCP诱导的新物体识别障碍模型小鼠的区分指数(t=-3.67、-2.12,均P<0.05及P<0.01),提高认知能力;而利培酮0.05 mg/kg对PCP诱导的新物体识别障碍模型小鼠的区分指数无显著性影响。(6)齐洛那平对D_(1)(Ki=3.21 nmol/L)、5-HT_(2A)(Ki=13.11 nmol/L)、5-HT_(6)(Ki=21.49 nmol/L)及5-HT_(2C)(Ki=48.90 nmol/L)受体有较高的亲和力,而对D_(2)(Ki=563.20 nmol/L)受体亲和力较弱。利培酮对5-HT_(2A)、5-HT_(2C)和D_(2)受体具有较高亲和力,其Ki分别为2.37、18.79和4.82 nmol/L,利培酮对D_(1

关键词：精神分裂症抗精神病药齐洛那平多巴胺受体

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