目的：探讨背侧海马CA1（ dCA1）区5-HT2A受体的亚细胞定位及与谷氨酸NMDA受体空间关系，观测系统性激活5-HT2A受体对dCA1区主神经元和中间神经元放电频率的影响。方法采用包埋后免疫电镜技术，观测dCA1区神经元内5-HT2A受体和NMDA受体的分布，采用多通道记录技术，记录腹腔注射TCB-2激活5-HT2A受体后主神经元和中间神经元放电频率的变化。结果5-HT2A受体在海马dCA1区神经元的粗面内质网、线粒体等处广泛分布，并在突触、突触小泡和神经丝等处与 NMDA 受体共区域表达；激活5-HT2A受体可致dCA1区主神经元的放电频率明显升高，而对中间神经元的放电频率无明显影响。结论 dCA1区5-HT2A受体可能通过与NMDA受体的协同作用，以增加谷氨酸能神经元的兴奋性，从而达到促进学习和记忆的作用。

Aim To examine subcellular localization of serotonin 5-HT2A receptor (5-HT2AR) and glutamate NMDA receptor in dorsal hippocampal CA1 area ( dCA1 ) and further explore the effect of systemic acti-vation of 5-HT2A R on hippocampal neuronal firing rate. Methods The distribution of 5-HT2A R and NMDA re-ceptor in the dCA1 region was detected with immune e-lectron microscopy after embedding. The effect of acti-vation of 5-HT2A R on the principal neuron and inter-neuron firing rates was examined with multichannel re-cording. Results 5-HT2A R immunoreactivity was ob-served in the dCA1 neurons, including rough endoplas-mic reticula and mitochondria, and the 5-HT2A R and glutamate NMDA receptors were colocalized in the syn-aptic membrane, vesicle and neurofilament of the hipp-ocampal neuron. 5-HT2A R activation increased princi-pal neuronal firing rate and the interneuronal firing rate was not changed. Conclusion The 5-HT2A R and NM-DA receptor are colocalized in dCA1 neurons, and acti-vation of

目的 证实胰高血糖素样肽1(GLP-1)受体在人肝星形细胞上的表达.方法 体外培养人肝星形细胞并进行形态学鉴定.提取肝星形细胞mRNA并逆转录获得cDNA,RT-PCR法测定GLP-1受体mR-NA的表达,免疫印迹法测定GLP-1受体蛋白的表达情况.结果 显微镜下可以观察到活化的肝星形细胞为扁平状,胞体大,具有发育良好的应力纤维,胞浆内缺乏脂肪滴.GLP-1受体cDNA片段长度为296 bp,与GenBank公布的人GLP-1受体cDNA序列(NM-002062.3)相符度为100％.免疫印迹法表明人肝星形细胞样本GLP-1受体蛋白表达阳性.结论 人肝星形细胞上存在GLP-1受体的表达.

Objective To confirm the expression of glucagon-like peptide 1 (GLP-1) receptor in human hepatic stellate cell (HSC).Methods Human HSC was cultured in vitro and morphologically identified.The mRNA of HSC was extracted and reversely transcribed to obtain cDNA.The mRNA of GLP-1 receptor was determined by RT-PCR.The GLP-1 receptor protein was determined by western blotting.Results The activating HSC were flat,with large cell body and well-developed stress fibers and without fat droplets in the cytoplasm under the microscope.The length of GLP-1 receptor cDNA fragment was 296 bp,which was 100％ consistent with the human GLP-1 receptor eDNA sequence (NM-002062.3) published in Gen Bank.The results of western blotting showed that there was GLP-1 receptor protein expressed in human HSC.Conclusions The GLP-1 receptor express in human HSC.

目的研究多巴胺受体介导的神经及生理活动。方法引进多巴胺D1和D3受体敲除小鼠,繁育出多巴胺D1D3受体双敲除小鼠。选择D1受体敲除、D3受体敲除、D1D3双基因敲除与WT四种基因型雄鼠各7只,对其30 d、50 d、70 d小鼠24 h内的进食量、饮水量及体重进行测量,探讨多巴胺D1受体、D3受体敲除小鼠及D1D3受体双基因敲除小鼠与野生型进食、饮水、体重增长的比较。结果多巴胺D1、D3受体基因对小鼠21 d和35 d的体重增长有一个较为显著的影响,直到90 d时,各基因型小鼠体重间无统计学差异。结论多巴胺可能通过调节HPA轴的活性,从而调控仔鼠的觅食与饱腹感,最终影响仔鼠初生重及泌乳期体重。同时,多巴胺D1、D3受体基因的敲除可能通过干扰泌乳等母性行为而影响小鼠的体重。研究结果为利用基因敲除小鼠研究多巴胺D1、D3受体的功能及它们之间的相互作用奠定坚实的基础。

Objective To study the effect of dopamine receptors on neurological and physiological activities. Methods Dopamine D1 receptor gene (DRD1) knockout mice and dopamine D3 receptor (DRD3) gene knockout mice were introduced, and double gene knockout mice were bred in our lab.Seven SPF male mice in each group were used in this experiment.The food intake, water intake, body weight gain for 24 hours were tested on the age of 30 d, 50 d, and 70 d and were compared with those of wild type mice.Results DRD1 gene and DRD3 gene showed significant effect on the body weight in mice in age of 21 day and 35 day, but at the age of 90 day, the differences became insignificant among the mice of various genetypes.Conclusions Dopamine may effect on the foraging and satiety in newborn mice through regulating the hypothalamic-pituitary-adrenal ( HPA ) axis activity, and finally leads to a reduced body weight gain in newborn mice and puppies during lactation.Furthermore, DRD1 gene and DRD3 gene may

目的：观察腺苷及腺苷受体激动剂对不稳定型心绞痛（UAP）患者白介素（IL）-18的影响，探讨腺苷受体的作用机制。方法选取15例UAP患者（UAP组）及15例健康志愿者（对照组），采用腺苷及腺苷受体激动剂干预全血标本，双抗体夹心酶联免疫吸附法（ELISA）检测IL-18。结果低浓度腺苷（1-100μmol/L）对UAP组IL-18表达有增强效应，高浓度（1 mmol/L）有抑制效应。腺苷A1受体激动剂与A3受体激动剂对IL-18表达有增强效应，而腺苷A2a受体激动剂对IL-18表达有抑制效应，腺苷A2b受体激动剂对IL-18表达未见明显效应。结论腺苷在低浓度时对UAP患者IL-18的表达有促进作用，可能通过腺苷A1和A3受体发挥效应；高浓度时有抑制作用，可能通过腺苷A2a受体发挥作用。

Objective To observe the effects of adenosine and adenosine receptor agonist on the expression of inter?leukin-18 (IL-18) in patients with unstable angina (UAP), and the mechanism of adenosine receptor agonists thereof. Meth?ods Fifteen UAP and 15 healthy volunteers were included in this study. The effects of adenosine and the selective adenos?ine receptor agonists on the expression of IL-18 were measured by enzyme-linked immunosorbent assay (ELISA). Results The lower concentration of adenosine (1-100μmol/L) increased the expression of IL-18 in UAP group;whereas the higher concentration of adenosine (1 mmol/L) inhibited the expression of IL-18. The adenosine A1 receptor agonist and A3 receptor agonist increased the expression of IL-18, while the adenosine A2a receptor agonist inhibited the expression of IL-18. There was no significant effect for A2b receptor agonist on the expression of IL-18. Conclusion The lower concentrations of ade?nosine can enhance the expression of IL

采用同源建模的方法构建了斑马鱼γ-氨基丁酸A型(GABA A)受体和果蝇RDL(resistance to dieldrin)受体跨膜区的三维结构,研究了氟虫腈在两个受体中作用位点的差异;采用分子对接和分子动力学方法,探讨了氟虫腈与斑马鱼GABA A受体和果蝇RDL受体的结合模式,并比较了氟虫腈与两个受体作用的差异性。结果表明:斑马鱼GABA A受体和氟虫腈作用位点的结构与果蝇RDL受体和氟虫腈作用位点的结构存在一定的差异,果蝇RDL受体中的Ala301对应斑马鱼GABA A受体α1亚基中的Val284和γ2亚基中的Ser306,氨基酸构象的差异较大;氟虫腈与斑马鱼GABA A受体的结合位点靠近胞内区一端,而与果蝇RDL受体的结合位点则位于受体第二跨膜区的Ala301~Leu308区域内。复合物分子动力学模拟结果表明,在模拟过程中,两个受体与氟虫腈复合物体系的势能可很快达到平衡状态。斑马鱼GABA A受体与氟虫腈之间形成4个氢键,其中概率大于60%的氢键有2个;而尽管果蝇RDL受体与氟虫腈形成了6个氢键,但只有1个氢键的概率大于50%,其复合物结合的稳定性比前者低。

The three-dimensional models of the transmembrane domain of zebrafish ( Danio rerio ) GABAA receptor and fruitfly ( Drosophila melanogaster) RDL receptor were constructed by homology modeling based on the pore structure of nicotinic acetylcholine receptor, and the differences of fipronil binding sites in the two receptors were discussed. Molecular docking and molecular dynamics wereused to investigate the different interactions between fipronil and the two receptors. The results indicated that the sequence identity was high, but the structure of fioronil binding sites in the two receptors were different. In zebrafish GABAA receptor, fipronil located at the bottom of the transmembrane domain, while in fruitfly RDL receptor, fipronil located within the region from Ala301 to Leu308. The two receptor-fipronil complexes were stable after molecular dynamics simulation. There were 4 hydrogen bonds generated between fipronil and zebrafish GABAA receptor, two of them whose frequency were higher