APP转基因小鼠脑组织中4.1B蛋白的表达研究

目的检测4.1B蛋白在阿尔茨海默病模型APP转基因小鼠脑组织中的表达。方法 PCR鉴定APP转基因阳性[APP（＋）]小鼠和APP转基因阴性[APP（﹣）]小鼠,分别取不同脑区用免疫组织化学法和免疫印迹法检测4.1B蛋白的表达。结果免疫组织化学法显示在APP（＋）鼠和APP（-）鼠的大脑皮层和海马均可见4.1B阳性细胞,APP（＋）组小鼠的4.1B蛋白表达明显高于APP（-）组小鼠。免疫印迹法检测APP（＋）组和APP（-）组小鼠脑组织海马、皮层和小脑中均有4.1B蛋白的表达,APP（＋）组各脑区4.1B蛋白表达均明显高于APP（-）组。结论 APP高表达引起脑组织内4.1B蛋白的表达增高。     

培哚普利通过调控脑锌代谢改善APP/PS1转基因小鼠认知功能

 目的 探讨培哚普利对APP/PS1转基因小鼠认知功能和大脑皮层锌、铁、锰、铜、镁、钙水平,以及锌转运体家族成员（ZnT1、ZnT2、ZnT3、ZnT4、ZnT5、ZnT6、ZnT7） mRNA表达水平的影响。方法 10只APP/PS1转基因小鼠随机分为对照组和培哚普利治疗组（各5只）。应用水迷宫实验检测小鼠认知功能;应用电感耦合等离子体质谱（inductively coupled plasma mass spectrometry,ICP-MS）检测小鼠大脑皮层6种金属微量元素的含量;应用real-time PCR检测小鼠大脑皮层锌转运体家族成员mRNA表达水平。结果 培哚普利降低了APP/PS1转基因小鼠逃避潜伏期,增加了小鼠穿越平台次数;培哚普利增加了APP/PS1转基因小鼠大脑皮层锌水平,而铁、锰、铜、镁、钙水平在培哚普利应用前后未见显著性差异;培哚普利降低了锌转运体家族成员中ZnT1的mRNA表达水平,而ZnT2、ZnT3、ZnT4、ZnT5、ZnT6、ZnT7 的表达水平在培哚普利应用前后未见显著性差异。结论 培哚普利可以通过下调大脑皮层ZnT1表达,调控脑锌代谢,进而改善APP/PS1转基因小鼠认知功能,提示调控脑内锌稳态是培哚普利改善阿尔茨海默病（Alzheimer's disease,AD）认知水平的重要机制之一。     

APP/PS1双转基因老年性痴呆小鼠早期病理和认知行为变化

【目的】探讨APP/PS1双转基因老年性痴呆(Alzheimer’s disease,AD)模型小鼠早期病理和行为学变化。【方法】选取5、7月龄的APP/PS1双转基因小鼠和非转基因小鼠,采用刚果红染色法和定量方法,并结合Morris水迷宫行为学测试,对其脑内淀粉样斑块积聚与学习记忆能力的月龄变化关系进行研究。【结果】(1)7月龄的双转基因组小鼠的空间辨别学习记忆能力与非转基因组小鼠比较差异有统计学意义(P<0.05);(2)APP/PS1双转基因组小鼠在5、7月龄时海马与脑皮质均观察到明显的橘红色斑块沉积,但非转基因组小鼠海马及脑皮质均未观察到淀粉样斑块沉积。【结论】7月龄APP/PS1双转基因小鼠的学习记忆能力下降,APP/PS1双转基因小鼠大脑皮层和海马部位淀粉样斑块的早期出现随年龄依赖性增加。     

五味子水提取液对APP/PS1小鼠大脑皮层神经细胞保护作用研究

目的:探讨五味子水提取液(SWE)对APP/PS1双转基因小鼠大脑皮层的神经细胞保护作用。方法:将C57BL/6小鼠分为正常组(Control),模型组(APP/PS1双转基因小鼠,Tg)和给药组(Tg+10、30、50 mg/kg的SWE,灌胃40 d);水迷宫检测各组小鼠的学习与记忆能力;Nissl法检测各组小鼠大脑皮层神经细胞的形态;TUNEL法检测各组小鼠大脑皮层神经细胞的凋亡情况;硫代巴比妥酸检测丙二醛(DMA)含量;黄嘌呤氧化酶法检测超氧化物歧化酶(SOD)活性。结果:与模型组比较,灌胃SWE明显提高Tg小鼠的学习与记忆能力;改善大脑皮层神经细胞的形态;减少神经细胞凋亡;显著降低MDA的含量以及增强SOD的活性。结论:SWE对Tg小鼠大脑皮层的神经细胞有一定的保护作用,可能是通过减轻氧化应激造成的损伤来发挥治疗作用。     

游离锌离子在APP/PS1转基因鼠脑老年斑内分布的研究

目的研究阿尔茨海默病(AD)动物模型-APP/PS1转基因鼠大脑内游离锌离子和β淀粉样蛋白前体蛋白(APP)在老年斑内的分布。方法分别应用浸入式锌金属自显影技术和APP免疫组织化学技术检测游离锌离子和APP在APP/PS1转基因鼠大脑内的分布。结果游离锌离子和APP免疫阳性反应产物均定位于老年斑内,新皮质和海马区域含有大量的老年斑,脑内其他部位有很少或没有老年斑。结论APP/PS1转基因鼠大脑β淀粉样蛋白(Aβ)老年斑内聚集着大量的锌离子,提示锌离子可能在Aβ老年斑的形成过程中起重要作用。     

丝裂原活化蛋白激酶家族在Swedish 突变的淀粉样前体蛋白 转基因鼠脑缺血中的作用

 【目的】 探讨丝裂原活化蛋白激酶家族(MAPK)在Swedish 突变的淀粉样前体蛋白(APP/SWE)转基因鼠脑缺血中的作用&#65377;【方法】 APP/SWE 转基因鼠与非转基因鼠各12 只应用光化学法诱导脑梗塞形成,缺血7 d后其中6只以尼氏染色对缺血半暗带区存活神经元进行定量分析,6只以Western blot方法检测p38MAPK和JNK的活性&#65377; 【结果】 缺血7 d后, 非转基因鼠组缺血半球海马区缺血半暗带存活神经元数目与非缺血半球镜像部位神经元数目的比值(78.3 ± 1.3)%与APP/SWE转基因鼠组(70.5 ± 1.4)%有统计学差异(P < 0.05);APP/SWE转基因鼠组缺血半球p38MAPK和JNK活性与非缺血半球有统计学差异(P < 0.05),而非转基因鼠组缺血半球p38MAPK和JNK活性与非缺血半球差异无统计学意义(P > 0.05)&#65377;【结论】 APP/SWE转基因鼠组缺血后脑损伤显著重于非转基因鼠组,可能的机制与丝裂原活化蛋白激酶过度激活促进脑缺血后细胞凋亡过程有关&#65377;     

多奈哌齐未能改善APP/PS1-AD转基因小鼠学习记忆功能的机制研究

目的探索多奈哌齐未能改善APP/PS1-AD转基因小鼠学习记忆功能的机制。方法选用9月龄野生型及APP/PS1-AD转基因小鼠分成野生型小鼠对照组、转基因小鼠对照组、转基因小鼠多奈哌齐1mg/kg组、转基因小鼠多奈哌齐3mg/kg组和转基因小鼠多奈哌齐6mg/kg组,每组20只,连续给药12周后实验动物心脏取血和分离其大脑皮层及海马组织,检测脑组织乙酰胆碱酯酶活性及茁-淀粉样蛋白（A茁）42含量,测定小鼠脑组织金属离子含量,采用免疫荧光法检测脑内A茁42淀粉样斑块沉积现象。结果多奈哌齐可显著降低APP/PS1-AD转基因小鼠大脑皮层组织的乙酰胆碱酯酶活性（P＜0.01）,且各剂量组作用强度相似,但对小鼠海马组织中乙酰胆碱酯酶活性没有显著影响;A茁42检测结果显示,多奈哌齐对各剂量组转基因小鼠的皮层和海马组织中A茁42含量无明显影响;免疫荧光法检测结果显示,多奈哌齐长期给药未能显著减少A茁42淀粉样斑块沉积;原子吸收光谱法测定结果显示,多奈哌齐对转基因小鼠大脑皮层组织镁离子、铜离子和钙离子浓度无明显影响。结论APP/PS1-AD转基因模型小鼠不能用于评价多奈哌齐类药物的药效。     

姜黄素对APP/PS1转基因鼠TNF-α、IL-6的影响

目的 探讨APP/PS1转基因鼠体内细胞因子TNF-α和IL-6的变化规律以及不同药量的姜黄素对其变化规律的影响.方法 6月龄雌性小鼠分为:野生型小鼠(对照组,n=9),APP/PS1转基因鼠(模型组,n=9)和APP/PS1转基因鼠+姜黄素(用药组,n=27).对照组和模型组自由摄食和饮水;用药组,姜黄素按60,160,600 mg·kg-1加入小鼠饲料,各组小鼠每次取3只分别于9,12,18月龄时处死,应用ELISA检测其大脑、血清中的细胞因子TNF-α和IL-6.结果 (1)与野生型小鼠相比,APP/PS1转基因鼠脑组织、血清中的TNF-α和IL-6于9月龄时开始升高,12月龄时差异显著(P＜0.05),18月龄时差异更加显著(P＜0.01);(2)应用姜黄素60mg·kg-1治疗后,APP/PS1转基因鼠脑组织、血清中的TNF-α和IL-6表达水平降低,姜黄素160mg·kg-1出现显著性差异(P＜0.05),姜黄素600 mg·kg-1差异更加显著(P＜0.01).结论 APP/PS1转基因鼠随着病情发展脑组织、血清中TNF-α和IL-6水平逐渐升高,应用姜黄素治疗后细胞因子TNF-α和IL-6逐渐降低,并呈剂量依赖性.     

唐氏综合征细胞黏附分子在APP转基因小鼠海马中的表达变化及其意义

目的  观察唐氏综合征细胞黏附分子（DSCAM）在淀粉样前蛋白（APP）转基因小鼠海马中的表达变化规律,探讨其意义。方法  选择月龄分别为1、3、6和12个月的APP转基因和野生型小鼠,应用免疫组织化学法对脑切片进行染色,观察DSCAM在APP转基因小鼠脑中的表达,应用蛋白免疫印迹法（Western blot）检测该蛋白在海马中表达量的变化规律,野生型小鼠做对照。结果  DSCAM主要在APP转基因小鼠大脑皮层、海马的锥体细胞中表达。在两组小鼠中,DSCAM在海马中的表达水平随年龄增长而下降（P <0.05）。DSCAM在APP转基因小鼠海马中的表达量明显高于同龄野生型小鼠（P <0.05）。结论  DSCAM在APP转基因小鼠海马内的过度表达可能在APP小鼠的学习和记忆能力下降中扮演重要角色。

     

APP/PS1+SCN2B-/-转基因小鼠模型的建立及鉴定

目的建立APP/PS1+SCN2B-/-转基因小鼠,为深入研究SCN2B基因在AD发生发展中的作用提供实验工具。方法将APP/PS1转基因小鼠与SCN2B-/-转基因小鼠合笼,子代同胞兄妹交配,子代的后代中选取APP/PS1高表达和SCN2B阴性的小鼠再同胞兄妹交配,并培育。得到的目的基因的小鼠与WT小鼠对照,进行表型鉴定。运用PCR鉴定子代小鼠尾部组织基因组DNA,用RT-PCR验证Aβ和SCN2B在大脑中的蛋白的表达,通过免疫荧光观察SCN2B在转基因小鼠神经系统中的表达,最后用水迷宫在行为学上对转基因鼠进行鉴定。结果经PCR鉴定成功构建APP/PS1+SCN2B-/-转基因鼠杂交群体,并扩群培育,经免疫染色和RT-PCR分析转基因小鼠的Aβ和SCN2B在大脑中的蛋白的表达,发现Aβ在转基因鼠的海马和皮质中高表达,SCN2B在海马中几乎检测不到,免疫染色也未发现SCN2B在神经系统中的表达。水迷宫结果显示转基因鼠与同月龄野生型(WT)小鼠相比在空间记忆和认知差异有统计学意义(P<0.05)。结论成功构建APP/PS1+SCN2B-/-转基因小鼠模型,从基因型、组织学表现到行为... 更多     

Value of D-Dimers in patients with acute aortic dissection

Objective: To evaluatel the value of D-dimers in patients with acute aortic dissection (AAD). Methods: This study consisted of 16 patients with AAD and 27 non-AAD patients. Serum D-dimets were measured by Sta-Liatest D-DI immunoturbidimetric assay. Results: D-dimer level was higher (P ＜ 0.001) in patients with AAD(7.91 ± 5.52 μg/ml) than that in non- AAD group(1.57±1.24 μg/ml). D-dimer was positive (＞0.4 μg/ml) in all patients with AAD and in 10 control group patients (37%). Among patients with acute AAD, D-dimers tended to be higher in Stanford A than in Stanford B (8.67 ± 4.31 μg/ml vs. 3.24±1.27 μg/ml, P ＜0.01). D-dimer values tended to be higher in more extended disease(3.84 ± 1.65 μg/ml, 8.57 ± 3.58 μg/ml and 11.87 ± 5.69 μg/ml in thoracic aorta, thoracic and abdominal aorta, thoracic and abdominal aorta and iliacal arteries, respectively, P ＜ 0.05 for both 8.57 ± 3.58 and 11.87 ± 5.69 vs. 3.84 ± 1.65 ). Including the control group into the analysis, we found a sensitivity of 100%, a negative predictive value of 100%, and a specificity of 66% and a positive predictive value of 64% for D-dimer in diagnosis of AAD in our patients with suspected AAD. Conclusion: D-dimer was elevated in patients with AAD. A negative D-dimer test result could be useful in excluding AAD.     

Research of combined liver-kidney transplantation model in rats

Objective： To set up a simple and reliable rat model of combined liver-kidney transplantation. Methods： SD rats served as both donors and recipients. 4℃ sodium lactate Ringer＇s was infused from portal veins to donated livers,and from abdominal aorta to donated kidneys, respectively. Anastomosis of the portal vein and the inferior vena cava （IVC） inferior to the right kidney between the graft and the recipient was performed by a double cuff method, then the superior hepatic vena cava with suture. A patch of donated renal artery was anastomosed to the recipient abdominal aorta. The urethra and bile duct were reconstructed with a simple inside bracket. Results： Among 65 cases of combined liver-kidney transplantation, the success rate in the late 40 cases was 77.5%. The function of the grafted liver and kidney remained normal. Conclusion： This rat model of combined liver-kidney transplantation can be established in common laboratory conditions with high success rate and meet the needs of renal transplantation experiment.     

BLOOD PRESSURE CHANGE WITH AGE IN SALT-SENSITIVE TEENAGERS

Objective To observe blood pressure change with age in salt-sensitive teenagers whose salt sensitivity were determined by repeated testing.Methods Salt sensitivity was determined through intravenous infusion of normal saline combined with volume-depletion by oral diuretic furosemide in 55 teenagers. After five years, salt sensitivity was re-examined and subject blood pressure was followed up. Blood pressure changes in salt-sensitive teenagers were compared to that of non-salt sensitive teenagers over five years.Results After 5 years, the repetition rate of salt sensitivity determined by intravenous saline loading is 92.7%. In teenagers with salt sensitivity on the baseline, both the systolic blood pressure increments and increment rates were much higher than non-salt sensitive teenagers (12.7±12.1 mmHg vs. 2.8±5.2 mmHg, P＜ 0.01; 12.2%± 12.0% vs. 2.5% ±4.4%, P＜ 0.001,respectively). There was a similar trend for diastolic blood pressure (8.4 ± 6.4 mmHg vs. 3.7 ± 6.4 mmHg, P = 0.052; 13.2% ±10.6 % vs. 6.8%± 10.1%, P = 0.053, respectively).Conclusions Salt sensitivity determined by intravenous saline loading showed good reproducibility. Blood pressure increments with age were much higher in salt-sensitive teenagers than non-salt sensitive teenagers, especially in terms of systolic blood pressure.     

APPLICATION OF LORNOXICAM TO PATIENT-CONTROLLED ANALGESIA IN PATIENTS UNDERGOING ABDOMINAL SURGERIES

FOR anesthesiologis s ,treatingpostoperativepainhas alwaysbeen a problem.Althoughopioidshave been provedtobe effective,theirsideeffectscouldnotbeignored.With thedevelopmentofscienceand pharmacology,many drugs with aspectsof satisfactoryanalgesicefficacyand couldbe welltoleratedby patientshave been developed.And lornoxicamisone of them, which isa non-steroidalanti-inflammatorydrug (NSAID ), with analgesic, anti-infl-ammatory,andantipyreticproperties.Itseliminationhalf-time(3 to 5 hours) isle…     

安心颗粒对急诊经皮冠状动脉介入术后生活质量影响的研究

目的：评价使用安心颗粒对急诊经皮冠状动脉介入术（PPCI）术后生活质量的影响.方法：将160例接受PPCI的急性ST段抬高型心肌梗死患者随机分为安心颗粒组（术前顿服安心颗粒8.8g,术后安心颗粒4.4 g/次,每日2次）和对照组（仅接受基础药物治疗）.所有患者均服用阿司匹林、氯吡格雷和阿托伐他汀.分别在入院时、出院前1d、出院后180 d时,应用心肌梗死多维度量表（MIDAS）、中文版SF-36评价量表对患者生活质量评分.并观察术后30 d以内的出血并发症、血小板减少症发生情况.结果：入院时和出院前1d,两组患者的心肌梗死MIDAS、SF-36量表评分比较无差异（P＞0.05）;出院后180 d时,与对照组比较,安心颗粒组MIDAS、SF-36评分明显减低（P＜0.05）;组内与入院时比较,两组出院前1d、出院后180 d时,MIDAS、SF-36评分均降低（P＜0.05）.两组患者在随访期间均无大量出血、少量出血、重度和极重度血小板减少症发生,安心颗粒组有4例、对照组有7例发生不明显出血（P＞0.05）.两组发生轻度血小板减少症的患者数比较无差异（P＞0.05）.结论：PPCI使用安心颗粒,能改善急性ST段抬高型心肌梗死患者的生活质量,且不增加出血风险.     

The comparative studies of the influences of Urapidil and Nicardipine on sino-atrial node function, atrio-ventricular node function and hemodynamics

Objective:To investigate the influences of urapidil and nicardipine on rabbit sinus function,atrio-ventricular node function and hemodynamics.Methods:Thirty-two Angora's rabbits were selected and randomly divided into four groups.U1 group:urapidil 0.25 mg/kg;U2 group:urapidil 0.5 mg/kg;N1 group:nicardipine 10 μg/kg;N2 group:nicardipine 20 μg/kg.All these medicine were administrated within 30 seconds.Measurements were taken before and after the administration of urapidil or nicardipine for the following data:mean blood pressure(MAP),heart rate(HR),sino-atrial conduction time(SACT),maximal sinoatrial recovery time(SNRTmax)corrected sinus node recovery time(CSNRT),index of sinus node recovery time(SNRTI),Wenckebach A-V conduction frequency (WB),and P-R interval.Results:Significant MAP and HR changes were identified in all of the four groups before and after administration of both urapidil and nicardipine.No significant changes could be found in the rest of the parameters.Intergroup analysis showed that SACT and CSNRT of N1 and N2 groups were shorter than those of the U2 group(P＜0.01);the MAP decreased(P＜0.01)and the HR increased drastically(P＜0.01).Conclusions:Neither urapidil(0.25 mg/kg,0.5 mg/kg)nor nicardipine(10μg/kg,20μg/kg)has any significant influence on rabbit sinus function or rabbit atrio-ventricular node function.Nicardipine could be a better choice than urapidil for parafunctional sinus node patients.     

Expression of OPGmRNA and ODFmRNA in the patients of hip fracture due to osteoporosis

Objective：To investigate the gene expression of osteoprotegerin（OPG） and osteoclast differentiation factor（ODF） in the bone tissue of patients with hip fracture due to osteoporosis. Methods：OPGmRNA and ODFmRNA in the bone tissue in 50 cases of osteoporosis sufferers（over 50 years old） with hip fracture（Observer Group） and 30 cases of hip facture sufferers with no osteoporosis（Control group） were analyzed with the Semi-Quantitative RT-PCR method. Results：The mRNA expressed of ODF, OPG were both high in the patients with hip fracture. In the control group, the expression of OPG mRNA was observed, while the expression of ODF mRNA was very slight. Conclusion：Aged patients contained all signals including OPG, ODF that are essential for inducing osteoclastogenesis and promoting bone resorption.     

Dynamic Changes in Serum Estradiol and Progesterone levels in Patients of Premenstrual Syndrome with Adverse Flow of Liver-qi

Objective:To probe into the influence of changes of ovarian hormones on the pathogenesis of the specific sub-type premenstrual syndrome(PMS)and reveal partial microcosmic mechanisms of adverse flow of liver-qi.Methods:Estradiol(E2)and progesterone(P)levels in serum were determined at different phases of menstrual cycle by radioimmunoassay.Results:In the group of PMS with adverse flow of liver-qi.the secretive peak value Of E2 and P at the follicular phase significantly decreased,and the secretive peak value at the luteal phase did not come into being.Conclusions:Low E2 and P secretive peak at the follicular phase and absence of secretive peak at the luteal phase is one of the microcosmic mechanisms of PMS with adverse flow of liver-qi.One of the pathophysiologic mechanisms of specific sub-type PMS is probably the continuous low level of E2and P.     

Real-time Three-dimensional Echocardiography in Assessment of Left Ventricular and Right Ventricular Volumes

Real-time three-dimensional echocardiography (RT3DE)is a new ultrasound technique that enables dynamic threedimensional visualization and quantification of the heart in real time. Investigation of feasibility and methodology of RT3DE in determining left ventricular (LV) and right ventricular (RV) volumes, RT3DE was performed in 35 normal adults using Philips SONOS 7500 system with a 2-4 MHz matrix array transducer. The 60°×60° "pyramid" volume database was obtained and analyzed on a TomTec echo workstation. Both LV and RV volumes were calculated with four 3DE methods (i.e. apical 2, 4, 8, and 16-plane) through manually tracing ventricular endocardial borders in end diastole and end systole. Stroke volumes were then calculated. LV volume was also measured by 2DE Simpson's rule using GE VIVID 7 ultrasound machine.     

SCREENING FOR A 21-CHROMOSOME ABNORMALITY IN PREIMPLANTED EMBRYOS OF ELDERLY WOMEN

Increasing maternal age is the only etiological factor unequivocally linked to Down's syndrome in humans. The occurrence rate of newborns with Down's syndrome is about 1/220 in women over 35 years old. However, the occurrence rate in embryos fertilized in vitro, of the elder woman is unclear. Using FISH we screened the number of chromosome 21 in preimplanted embryos of 5 elderly women (average age, 38.4 years) to study the feasibility and necessity of screening trisomy 21 in embryos in patients over 35 years old at the in vitro fertilization (IVF) center.