姜黄素对6-羟基多巴胺所致大鼠拟帕金森病的保护作用

目的:研究姜黄素对单侧黑质区6-羟基多巴胺注射所致大鼠拟帕金森病的保护效应.方法:选用健康雄性SD大鼠,随机分为4组,包括正常对照组、姜黄素组、6-羟基多巴胺组、6-羟基多巴胺+姜黄素组.6-羟基多巴胺被注射入6-羟基多巴胺组和6-羟基多巴胺+姜黄素组大鼠单侧黑质区,制备拟帕金森病模型.6-羟基多巴胺注射后2周,大鼠经阿扑吗啡诱导进行旋转行为实验,评估帕金森病模型制备是否成功.在旋转行为实验完成的第二天,姜黄素以100mg/kg剂量灌胃,1次/d,持续4周.给予姜黄素4周后,处死大鼠,采用高效液相色谱法检测大鼠纹状体中多巴胺含量.结果:经姜黄素处理的拟帕金森病大鼠纹状体区的多巴胺水平明显升高.结论:姜黄素对6-羟基多巴胺所致大鼠拟帕金森病具有保护效应.     

人参皂苷Rg1的抗抑郁作用及其作用机制

目的：观察人参皂苷Rg1的抗抑郁作用,探讨其抗抑郁机制。方法：采用小鼠悬尾实验（tail suspension test,TST）和强迫游泳实验（forced swim test,FST）建立急性应激模型,选择大鼠慢性温和不可预见性应激（chronic unpredictable mild stress,CUMS）的方法建立长期抑郁模型。同时给予人参皂苷Rg1（5,10,20 mg·kg-1·d-1）和度洛西汀（10 mg·kg-1·d-1）,观察Rg1的抗抑郁作用。结果：在急性应激实验中,Rg1三个剂量组（5,10,20 mg·kg-1）均能够显著减少动物的不动时间。慢性应激后,采用强迫游泳和糖水消耗实验进行行为学检测,与模型组相比,Rg1三个剂量均能够显著减少大鼠在强迫游泳实验中的不动时间,增加糖水偏好实验的糖水消耗百分比,延长动物的睡眠时间。机制研究证明,Rg1可抑制PDE4引起环腺苷酸（cyclic adenosine monophsphate,cAMP）的累积,进而激活cAMP介导的抗抑郁信号转导途径,还可增加雄激素水平,而雄激素又能拮抗糖皮质激素的释放和增加基础突触传递。此外,增加突触新生也是抗抑郁的重要机制。结论：人参皂苷Rg1对小鼠急性应激和CUMS诱导的大鼠抑郁行为有显著的改善作用,并可能通过调节神经递质和激素的释放、减少糖皮质激素含量、增加神经营养因子的表达以及增强突触可塑性来发挥抗抑郁作用。     

新型组蛋白去乙酰化酶抑制剂DWP0016诱导神经胶质瘤细胞U251周期阻滞及凋亡作用研究

目的:观察新型组蛋白去乙酰化酶( Histone Deacetylases,HDACs)抑制剂DWP0016对神经胶质瘤U251细胞株的作用,探讨诱导U251细胞周期阻滞及凋亡作用的机制.方法:采用噻唑蓝(MTT)法检测DWP0016对U251细胞株的增殖抑制作用;采用流式细胞术观察DWP0016对U251细胞周期的影响及凋亡诱导作用;采用实时定量PCR(real-time PCR)检测抑癌因子P21,P53的mRNA水平变化;蛋白免疫印迹法(Western blotting)测定Ac-H3,P21,P53,Pi3K,p-Pi3K,Akt,p-Akt的蛋白表达并进行光密度定量.结果:DWP0016抑制U251细胞增殖的半数抑制浓度(IC50=0.531 μmol·L-1)明显低于阳性对照奥沙利铂(IC50=4.792 μmol·L-1),组蛋白H3乙酰化水平显著上升;DWP0016作用后,U251细胞中细胞周期阻滞于G1期并产生凋亡,P21,P53的mRNA水平和蛋白水平明显上升,Pi3K/Akt通路中的Pi3K,Akt的磷酸化水平下降.结论:DWP0016能明显抑制U251细胞增殖,诱导细胞周期阻滞和凋亡产生,其机制与促进抑癌因子P21,P53的转录及蛋白表达,抑制细胞中Pi3K/Akt生长信号通路有关,具有良好的抗神经胶质瘤潜力和开发应用前景.     

原花青素联用胡椒碱减轻抑郁样行为的机制研究

目的：探讨原花青素（proanthocyanidin,OPC）不同剂量联用胡椒碱（piperine,PIP）的抗抑郁样行为及其机制.方法：采用慢性不可预知性温和应激模型,连续造模联合给药21d后,d 22测定小鼠悬尾、强迫游泳不动时间;用高效液相电化学法测定小鼠海马和前额叶皮层中单胺递质及其代谢产物的含量,荧光分光光度法检测全脑单胺氧化酶活性.结果：与正常组相比,模型组小鼠悬尾和强迫游泳测试中的不动时间显著增加;同时其海马、前额叶皮层中5-羟色胺（5-hydroxytryptamine,5-HT）、去甲肾上腺素（norepinephrine,NE）含量显著下降,但5-羟吲哚乙酸（5-hydroxyindoleacetic acid,5-HIAA）与5-HT比值（5-HIAA/5-HT）显著上升.OPC （50、25、12.5 mg·kg-1）剂量组联用PIP（5 mg·kg-1）能够逆转这种现象.此外,OPC （50、25、12.5 mg·kg-1）剂量组联用胡椒碱（5 mg·kg-1）组还能降低由于应激引起的单胺氧化酶（monoamine oxidase,MAO）A型活性升高,但不影响单胺氧化酶B型活性.结论：原花青素联用胡椒碱可以改善由于慢性应激对小鼠造成的抑郁样行为,其机制可能与降低单胺氧化酶活性,增加单胺递质含量有关.     

雌激素和Glu-NMDA受体通路与学习记忆相关性的研究进展

雌激素(estrogen,E)是维持女性第二性征最主要的甾体物质,其在神经系统也发挥广泛的药理作用,如抗脑缺血再灌注损伤减少梗死面积,抗自由基形成,调节兴奋性氨基酸释放等.雌激素自身作为一种抗氧化剂能够通过调节体内氧化还原平衡发挥神经保护作用.另外,雌激素在神经系统药理作用的发挥与其受体密不可分,经典的雌激素受体(estrogen receptor, ER)主要位于细胞核内,包括ER-α和ER-β两种亚型,二者均可在大脑皮质和海马表达:卵巢切除大鼠学习记忆能力降低的同时,ER-α在大脑皮质区和海马区表达也显著减少;ER-β基因敲除能够严重影响学习记忆行为、长时程增强(long term potentiation,LTP)和突触强度,该受体可能参与了高级脑功能的调节.N-甲基-D-天冬氨酸(N-methyl-D-aspartic acid,NMDA)受体作为与学习记忆密切相关的受体,与雌激素受体在海马区存在共表达.雌激素可能通过膜相关的雌激素受体快速激活ERK1/2信号转导通路,进一步诱导NMDA受体NR2B亚基磷酸化,激活NMDA受体,三者均会影响突触可塑性.本文就雌激素及其受体和Glu-NMDA受体通路与学习记忆的相关性进行综述.     

阿托伐他汀抑制TRPM2表达和开放对血管内皮氧化应激的影响

为探讨阿托伐他汀对瞬时受体电位通道M2(TRPM2)表达和功能的影响,及其在血管内皮氧化应激损伤中的作用,通过western bloting和细胞钙荧光测定,观察阿托伐他汀预处理对小鼠主动脉内皮细胞TRPM2蛋白表达水平和通道开放的影响,并采用离体主动脉环灌流技术,观察阿托伐他汀对H₂O₂诱导血管内皮功能损伤的改善作用.研究结果表明：经阿托伐他汀预处理7天,可降低小鼠主动脉内皮细胞TRPM2蛋白的表达水平,抑制H₂O₂引起的TRPM2通道开放介导的细胞内钙升高,减轻H₂O₂引起的内皮细胞死亡;经阿托伐他汀急性预处理30 min,可抑制H₂O₂引起的细胞内钙升高;经阿托伐他汀灌胃14天,可减轻H₂O₂引起的小鼠主动脉环内皮依赖性舒张功能损伤;在TRPM2基因敲除小鼠内,阿托伐他汀对血管舒张功能无明显保护作用.由此可见,阿托伐他汀可通过抑制TRPM2通道的表达和开放来减轻血...     

Imbalanced free radicals and antioxidant defense systems in schizophrenia： A comparative study

Objective： To examine changes of blood oxidative-antiovidative level in schizophrenic patients and its relationship with clinical symptoms. Methods： Forty-six Chinese patients met DSM-IV （Diagnostic and Statistical Manual of Mental Disorders-iV） criteria for schizophrenia and fifty age- and sex-matched healthy controls were enrolled in the present study. Baseline psychiatric symptom severity was assessed with brief psychiatric rating scale, positive and negative syndrome scale on the blood draw day. Fresh blood samples were collected to measure levels of nitric oxide and lipid peroxide in plasma as well as activities of superoxide dismutase, catalase and glutathione peroxidase in red blood cells by spectrophotometric assays simultaneously. Results Comparison of the biochemical parameters indicated that the level of nitric oxide and lipid peroxide increased in patient group, which represented a positive correlation with positive scale scores; while the activities of three critical enzymes decreased and showed a negative linear correlation. Conclusion： This study showed that there are dysregulation of free radical metabolism and poor activities of the antioxidant defense systems in schizophrenic patients. Excess free radicals formation may play a critical role in the etiology of schizophrenia. Using antioxidants might be an effective therapeutic approach to partially alleviate or prevent the symptoms of schizophrenia.     

Vibration response analysis of floating slab track supported by nonlinear quasi-zero-stiffness vibration isolators

To improve the low-frequency vibration reduction effect of a steel spring floating slab track(FST), nonlinear quasizero-stiffness(QZS) vibration isolators composed of positive stiffness elements(PSEs) and negative stiffness elements(NSEs) were used to support the FST. First, considering the mechanical characteristics of the nonlinear QZS vibration isolators and the dynamic displacement limit(3 mm) of the FST, the feasible parameter groups were studied with the nonlinear stiffness variation range and bearing capacity as evaluation indices. A vertical vehicle quasi-zero-stiffness floating slab track(QZS-FST) coupled dynamic model was then established. To obtain a reasonable nonlinear stiffness within a few millimeters, the original length of the NSEs must be analyzed first, because it chiefly determines the stiffness nonlinearity level. The compression length of the NSEs at the equilibrium position must be determined to obtain the low stiffness of the floating slab without vehicle load. Meanwhile, to meet the dynamic displacement limit of the FST, the PSE stiffness must be increased to obtain a higher stiffness at the critical dynamic displacement. Various stiffness groups for the PSEs and NSEs can provide the same dynamic bearing capacity and yet have a significantly different vibration reduction effect. Excessive stiffness nonlinearity levels cannot effectively improve the vibration reduction effect at the natural frequency. Furthermore, they also significantly amplify the vibrations above the natural frequency. In this paper, the vertical vibration acceleration level(VAL) of the floating slab and the supporting force of the FST can be decreased by 6.9 dB and 55%, respectively, at the resonance frequency.     

Experimental and thermal stress investigation on side wall deformation at the pendent convective pass in a utility boiler

An experimental investigation is performed on side wall deformation at the pendant convective pass （PCP） in a 300 MW and a 600 MW utility boiler. The temperature distributions are measured on the side wall areas of the water-cooled wall, the PCP and the horizontal convective pass （HCP） in the two utility boilers. These experiments show that there are great temperature differences in the side wall areas during the startup process in both utility boilers. These temperature differences can reach 80-150 ~C with the side wall temperature in the PCP area higher than those in the water-cooled wall and the HCP. The highest temperature in the PCP is close to the flue gas side temperature at the same position in the horizontal flue gas pass. Thermal stress analyses are conducted in the side wall areas in the water-cooled wall, the PCP and the HCP with the software ANSYS. The results show that, at great temperature differences, the PCP side wall undergoes negative thermal stresses that exceed the yield strength causing deformation in the PCP side wall.     

Akt信号通路与缺血性脑卒中

本文综述了Akt的生物学及其在缺血性脑卒中的病理生理作用,并介绍了最新的相关研究进展。Akt在脑缺血再灌注损伤中呈现高磷酸化表达,对脑组织损伤有保护作用。最新研究提示,Akt具有应激反应的特征,对脑的保护作用与其它通路的协同启动有关。对Akt的深入研究将有助于对其在脑卒中作用的深入理解,也有助于相应药物的研发。     

小鼠条件性电击社交恐惧行为模型的建立与评价

目的：建立稳定而特异性强的小鼠社交恐惧行为模型。方法：采用针对社交接触行为给予条件性足底电击（O．7mA,1S,1～5次）的方式建立小鼠社交恐惧模型。分别于电击后d2和d15检测小鼠的社交探究行为,以探究时间百分比（investigationtime％,1T％）为社交恐惧行为评价指标。分别采用小鼠高架十宁迷宫实验、明暗穿箱实验和强迫性游泳实验评价小鼠的广泛性焦虑行为和抑郁样行为。结果：在条件性电击后d2和d15的社交探究实验中,与非丰十交刺激（non．socialstimulus,NSS）组比较,条件性社交刺激（conditionedsocialstimulus,CSS）组小鼠IT％均显著减少。在小鼠高架十字迷宫实验、明暗穿箱实验和强迫性游泳实验上,CSS组与NSS组各行为指标差异均无显著意义。结论：采用条件性足底电击方式可成功建立小鼠社交恐惧行为模型,模型症状可持续至少2周,且不伴随广泛性焦虑行为或抑郁样行为,具有良好的稳定性和特异性。     

Effects of Expressive Writing Effects on Disgust and Anxiety in a Subsequent Dissection

Emotions influence motivation and achievement, but negative emotions have rarely been assessed in science education. In this study, we assessed the influence of two different expressive writing assignments on disgust and anxiety in university students prior to the dissection of a trout. We randomly assigned students to one of two expressive writing tasks and measured specific state disgust and state anxiety after writing and after the dissection. Specific state disgust was measured a third time after 3 weeks. One writing task was concerned with the dissection, and the other was related to behavioral experiments with mice. We used two general linear models with repeated measures. In the first model, specific state disgust (pre, post, and follow-up) was used as the dependent repeated measure and experimental group as the independent variable. In the second model, state anxiety was used as the dependent repeated measure (pre, post) with experimental group as the independent variable. The repeated testing showed a highly significant effect of experimental group on the repeated measures of disgust. Writing about worries and emotions concerning the dissection leads to higher disgust scores compared to writing about mice. These higher scores persisted even 3 weeks later in the follow-up test. Concerning anxiety, there was a clear influence of the repeated measure of state anxiety, but anxiety was not influenced by the experimental group. We suggest that positive writing should be used in educational contexts to reduce disgust.     

舒尼替尼对结肠成纤维细胞体内外抑制机制研究(英文)

研究目的:探索小分子酪氨酸激酶抑制剂舒尼替尼(sunitinib)对结肠肿瘤微环境中的肿瘤相关成纤维细胞的作用及其机制。创新要点:舒尼替尼通过抑制肿瘤间质成纤维细胞的生长,间接发挥抗肿瘤效应,为结肠癌综合治疗的提供新途径。研究方法:通过细胞周期分析和细胞增殖测定进行舒尼替尼体外抑制肿瘤细胞的研究。采用Western-blot检测磷酸化血小板衍生生长因子β受体(PDGFR-β)、蛋白激酶B(Akt)及细胞外信号调节蛋白激酶(ERK)的蛋白水平。通过注射肠腺癌细胞株SW620和结肠成纤维细胞构建的裸鼠移植瘤模型来研究舒尼替尼的体内抑瘤效果。重要结论:舒尼替尼可有效抑制结肠癌来源的原代结肠成纤维细胞生长,该抑制作用主要通过抑制血小板衍生生长因子(PDGF)信号通路得以实现。     

社区精神分裂症患者攻击行为的相关因素研究

对95例随机抽取的社区精神分裂症患者进行评估,比较33例一年内发生攻击行为患者和62例一年内无攻击行为患者的差异,并进行logistics回归分析,探讨社区精神分裂症患者攻击行为的相关因素．结果显示,2组患者精神病阳性症状数目、患者文化程度、患者的自知力、监护人的文化程度,比较有统计学意义（p〈0．05）．logistic回归分析显示患者的阳性症状数目、自知力和患者文化程度与攻击行为相关．社区精神分裂症出现攻击行为患者阳性症状更多,文化程度低、监护人文化程度较低、自知力较差、阳性症状数目、患者文化程度以及患者的自知力与精神分裂症患者的攻击行为相关．     

舍曲林联合舒必利治疗精神分裂症的临床研究

目的:探讨舍曲林合并舒必利治疗精神分裂症的疗效和安全性.方法:将60例符合CCMD-3诊断标准的精神分裂症患者随机分为研究组和对照组,研究组给予舍曲林合并舒必利治疗,对照组服用阿立哌唑,疗程8周,用PANSS、TESS评定疗效和安全性.结果:研究结束时舍曲林合并舒必利组总有效率为86.7%,阿立哌唑组总有效率83.3%,两组比较无显著性差异(P>0.05).两组不良反应少且轻.结论:采用舍曲林合并舒必利的方法治疗精神分裂症疗效可靠,安全性好,值得进一步研究.     

EGCG对肝癌细胞株BEL-7402增殖凋亡及Stat3蛋白表达的影响

研究了没食子儿茶素没食子酸酯（EGCG）对人肝癌细胞BEL-7402增殖凋亡及对信号转导蛋白和转录激活因子3（Stat3）蛋白及磷酸化Stat3蛋白表达的影响.应用MTT法检测不同浓度EGCG对BEL-7402细胞增殖的抑制作用,用流式细胞仪分析细胞的凋亡率,用ELISA方法检测EGCG对Stat3蛋白及磷酸化的Stat3蛋白表达的影响.结果表明：EGCG有抑制肝癌细胞增殖促进凋亡的作用,并呈剂量依赖性.ELISA结果显示EGCG能降低磷酸化Stat3蛋白的表达水平.EGCG能抑制肝癌细胞的增殖促进凋亡,其机制可能有与下调磷酸化的Stat3蛋白的表达有关.