雌激素及其拮抗剂对大鼠脂代谢和血管活性肽水平的影响

以假手术大鼠（Sham）作为对照组,切除大鼠双侧卵巢（OVX）后,血浆17β-雌二醇（17β-E2）水平下降48％。体重增加17％（P＜0．001）,血清总胆固醇（TC）含量升高约50％（P＜0．001）,甘油三酯（TG）含量降低30％（P＜0．01）。OVX后进行雌激素替代疗法（ERT）各组（ERT1-3）的TC和TG的含量分别下降（P＞0．05）到和升高（P＜0．01）至高于对照组的水平。给于雌激素受体拮抗剂──它莫西芬（TAM）的各组（TAM,OVX＋TAM,ERT3＋TAM）中,血清TC和TG含量均低于对照组（P＜0．01～P＜0．001）。此外,OVX组血浆降钙素基因相关肽（CGRP）和内皮素水平也分别降低为对照组的69％和89％（P＜0．05）。提示卵巢激素主要是雌激素通过其受体介导参与大鼠脂代谢和体重的调节,ERT和TAM对OVX大鼠血清TC浓度及体重的调节产生有利影响。OVX大鼠血浆CGRP和内皮素水平的调节可能与雌激素水平变化有关。     

SLE患者外周血中T、B细胞表面Fas和bcl—2表达的研究

目的 探讨活动期SLE患者外周血中T、B细胞表面Fas和bcl-2的表达水平及其与T、B细胞凋亡的关系。方法 采用流式细胞术,测定活动期SLE患者外周血T、B细胞表面Fas和bcl-2的表达,并同时测定患者血中T、B细胞的凋亡。结果 ①活动期SLE患者外周血中B细胞及CD8T细胞表面bcl-2的表达明显高于正常人（分别为P＜0．05）和P＜0．01）;CD4^ 及CD8^ T细胞表面Fas的表达高于正常人（分别为P＜0．05和P＜0．01）;B细胞表面Fas的表达降低（P＜0．01）;CD4^ T细胞bcl-2的表达下降（P＜0．01）。②活动期SLE患者血中B细胞的凋亡率明显下降,CD8^ T细胞数校正常对照组增加,CD4^ T细胞低于正常人（分别为：P＜0．01、P＜0．05和P＜0．01）。结论 SLE患者体内淋巴细胞凋亡的异常与T、B细胞表面Fas和bcl-2基因的表达的异常有关。     

中药复方对X线照射小鼠T淋巴细胞亚群和抗氧化能力的作用

目的：通过观察X线照射后小鼠T淋巴细胞亚群和抗氧化酶的变化，探讨辐射小鼠抗氧化酶和T淋巴细胞亚群的相互关系及中药养阴抗毒散的放射防护作用机理。方法：采用间接免疫荧光法和流式细胞仪测定小鼠外周血T淋巴细胞亚群，采用化学比色法测定总抗氧化能力（T－aoc)、过氧化氢酶（Cat)、超氧化物歧化酶（SOD）及丙二醛（MDA）。结果：和正常对照组比较，两个照射组CD4、CD8亚群的比例无显著下降（P＜0．01），照射对照组CD4／CD8小于正常对照组（P＜0．01）；照射中药组CD4亚群比例及CD4／CD8均高于照射对照组（P＜0．01），CD8亚群比例两者无显著差异。与正常对照组比较，照射对照组的抗氧化能力或酶类均显著降低（P＜0．01，P＜0．05），而丙二醛显著升高（P＜0．01）；照射中药组仅有过氧化氢酶下降（P＜0．01），丙二醛也显著升高（P＜0．01）；照射中药组与照射对照组比较，过氧化氢酶升高（P＜0．01），而丙二醛降低（P＜0．01）。结论：养阴抗毒散对X线照射小鼠T淋巴细胞亚群的减少有一定改善，它可能通过提高小鼠抗氧化能力达到此作用。     

盐酸戊乙奎醚用于新生儿麻醉前用药的研究

目的观察比较盐酸戊乙奎醚和阿托品用于新生儿手术全身麻醉前用药的临床效果。方法30例新生儿手术患者．根据麻醉前用药的不同随机分为盐酸戊乙奎醚组（P组）和阿托品组（A组）,每组15例,分别在麻醉开始前30min肌肉注射盐酸戊乙奎醚或阿托品0．02mg／kg。记录给药前（T0）、给药后15min（T1）和30min（T2）时患儿的血压（BP）、心率（HR）、脉搏血氧饱和度（SPO2）及T0、T1、T2和气管导管拔除时（T3）患儿面红、腺体分泌情况。结果2组患儿性别、年龄、体重和手术时间无统计学差异（P〉0．05）;P组术前给药后HR、BP无明显改变（P〉0．05）,A组给药后HR均明显增快．与P组比较差异有统计学意义（P〈0．05）;P组与A组比较,气管拔管时分泌物量明显减少（P〈0．05）,且面红发生率较低（P〈0．05）。结论盐酸戊乙奎醚具有显著的心率稳定作用及强大持久的腺体分泌抑制作用．作为术前用药效果满意．优于阿托品．可安全用于新生儿手术麻醉前给药．     

亮氨酸脑啡肽与TRH-TSH-甲状腺轴互相影响的研究

目的：探索阿片类物质与TRH－TSH－甲状腺轴之间的关系的相互影响。方法：制造大鼠高甲状腺激素水平及低甲状腺激素水平动物模型,用放免法测定甲状腺激素（T3、T4、TRH、TSH）、鸦片类物质亮氨酸脑啡肽（L－EK）及用高压液相－电化学法测定神经递质5－羟色胺（5－HT）。结果：高甲组T3、T4呈逐渐升高（P＜0．01）;血清TRH迅速下降以后又回升;下丘脑TRH呈持续抑制状态,TSH显著降低（P＜0．001）,L－EK升高（P＜0．05）,5－HT降低（P＜0．05）。低甲组T3、T4显著降低（P＜0．001）,血清TSH、TRH含量逐渐升高（P＜0．001）,垂体TSH、下丘脑TRH含量逐渐降低（P＜0．01）,以后又回升;L－EK升高,5－HT降低（P＜0．01）。结论：甲状腺功能改变后TRH、TSH升高而降低,并不伴随脑纹状体中L－EK必然的同步升高而降低。     

更年期综合征妇女雌激素替代治疗的研究

目的：探讨更年期综合征妇女激素替代治疗相关指标的变化及其临床意义。方法：采用放射免疫分析法、离子电极法及酶法测定了50例更年期综合征患者血清E2、FSH、LH、TC、TG、LDL、HDL、ALP水平及尿Ca/Cr比值。结果：经激素替代治疗，患者改良Kuppormen评分显著下降（P＜0．05，P＜0．01）TC、TG及LDL亦显著下降（P＜0．05），HDL略有上升，但统计差异无显著性（P＞0．05）；E2水平明显升高（P＜0．05），FSH及LH则显著下降（P＜0．05），ALP治疗前后无显著差异（P＞0．05），Ca/Cr比值显著下降（P＜0．05）。结论：研究证实，激素替代治疗更年期综合征有满意疗效。     

过敏性紫癜患儿外周血单个核细胞 TLR2、TLR4表达及其与 Th1和 Th2型免疫应答相关性观察北大核心CSCD

目的：研究Toll样受体（Toll-like receptor,TLR）2、TLR4在过敏性紫癜（HSP）患儿外周血单核细胞的表达及其与Th1和Th2型免疫应答的相关性,探讨TLR2、TLR4在HSP发病机制中的作用。方法选取2011年10月-2012年11月于我院儿内科收治的HSP患儿64例为研究对象,分为HSP无肾损害组（NHSPN,36例）及HSP有肾损害组（HSPN,28例）,另选取我院儿保科健康查体儿童30例作为正常对照组。采用流式细胞术检测外周血T淋巴细胞亚群及单核细胞TLR2及TLR4蛋白表达,实时荧光定量PCR技术检测外周血单核细胞TLR2 mRNA及TLR4 mRNA的基因相对表达量,ELISA法检测血浆IFN-γ、IL-4、IL-6水平。结果（1） HSP 患儿外周血单核细胞TLR2 mRNA、TLR4 mRNA相对表达量及TLR2、TLR4蛋白表达均显著高于正常对照组（P均＜0．01）,HSPN组外周血单核细胞TLR2 mRNA、TLR4 mRNA相对表达量及TLR2、TLR4蛋白表达均明显高于NHSPN组（P＜0．05;P＜0．01;P＜0．01;P＜0．01）。（2）HSP组CD3＋T细胞、CD3＋CD4＋T细胞显著降低,CD3＋CD8＋T细胞及CD3＋HLADR＋活化T细胞明显升高（P均＜0．01）。（3）HSP组血浆IL-4、IL-6水平显著高于正常对照组（P＜0．01,P＜0．01）,IFN-γ水平显著低于正常对照组（P＜0．05）,IFN-γ/IL-4比值显著低于对照组（P＜0．01）。（4）HSP组TLR2、TLR4蛋白表达与血浆IL-4、IL-6水平均呈显著正相关（P＜0．01,P＜0．05;P＜0．01,P＜0．01）;与IFN-γ/IL-4比值均呈显著负相关（P＜0．01;P＜0．01）。结论TLR2及TLR4活化可能参与了HSP的免疫发病机制,TLR2及TLR4的过度活化可能与HSP的肾损伤有关。 HSP患儿存在T淋巴细胞亚群失调,功能紊乱,Th1/Th2失衡。活化的TLR2及TLR4可能通过上调Th2型免疫应答介导HSP的免疫发病机制。     

流行性出血热患者红细胞变形性的研究──附124例临床分析

观察124例流行性出血热（EHF）患者治疗前红细胞变形能力（RCD）明显低于对照组（P＜0．01）；治疗前明显低于治疗后（P＜0．01）。RCD于发热期开始下降，休克期及少尿期下降更显著（P＜0．01）。进入多尿期开始上升,至恢复期已基本转为正常（P＞0．05）。病情越重，RCD下降越显著（P＜0．01）。治愈者完全恢复正常，无效者未见明显改善。本病RCD下降与EHF病毒所致全身性微血管损伤有关。在本病综合治疗的同时，采取提高RCD的措施，有助患者的康复。     

高血压和冠心病患者的血液流变性研究

本文对245名高血压和冠心病患者进行血液流变学、纤维蛋白原和血脂测定。结果表明，患者的全血粘度（ηb）、血浆粘度（ηp）、血沉（ESR）、K值、红细胞电泳时间（ET）、纤维蛋白原（Fg）、胆固醇（TC）和甘油三酯（TG）含量均大于或高于正常人（P＜0．01）。高血压的ESR，K值和TG高于冠心病，差异显著（P＜0．01），其它指标相似。高血压的各项指标与高血压合并冠心病比较无差异（P＞0．05）；而高血压合并冠心病的ESR，K值和TG值显著高于冠心病（P＜0．05）。TC有所增加（P＜0．05）。     

老年慢性精神分裂症患者脑电地形图初步研究

目的：为探讨老年慢性精神分裂症患者（SCS）与正常老人在脑电地形图（BEAM）检查中的各自特点。方法：使用16道地形图仪，对39例正常老人和24例SCS患者的BEAM作了检测。结果：在头颅模式图中，SCS患者的BEAM趋向凹字形低密度带。在前颞区θ频域及枕区和中央区δ频域均右侧高于左侧（P＜0．05）。与正常老人相比，SCS患者δ与θ波功率在主要记录点均增高（P＜0．05或P＜0．01）。α波功率在F3、F4、P3、P4以及Fp1、F7记录点下降（P＜0．01或P＜0．05）。β波功率在主要记录点（Fp1、Fp2、T3、T4、T5、T6、O1、O2、F3、F4）上降低也有显著性差异（P＜0．05）。SCS患者BEAM－EEG比EEG提高阳性检出率12．5％。结论：SCS患者的BEAM－EEG具有不同于正常衰老的改变。     

湖北麻鸭乙型肝炎病毒体内感染模型的建立

目的 建立标准化的湖北麻鸭乙型肝炎病毒(DHBV)动物模型,并初步观察拉米呋啶(3TC)体内抗DHBV的作用.方法将收集的转染细胞培养上清液纯化后作为体内实验感染的标准毒种,经腹腔接种2日龄雏鸭,连续观察50 d,用Real-Time PCR检测血清中DHBV DNA出现和持续时间.药物组则于接种3 d后给予3TC,检测观察期间感染鸭血清中病毒含量的变化情况.结果雏鸭实验感染率达到87.5%;雏鸭在接种后第7天出现病毒血症,血清病毒含量于第11天达到高峰值,后逐步降低,但在观察期内仍维持较高水平.在3TC治疗期间,感染鸭体内病毒血症处于较低水平,被感染肝细胞的数量也明显减少,且无明显的毒性作用;在停药3 d后,病毒血症即出现反跳现象,此后又有上升趋势.结论通过接种转染细胞上清液成功建立湖北麻鸭乙型肝炎病毒动物模型,药物评估实验证明其良好的稳定性和实用性;该模型也为研究DHBV生物学特性提供了有力的手段.     

新型核苷衍生物十八烷氧乙基替诺福韦酯的体内外抗乙型肝炎病毒作用研究

目的 评价新型核苷衍生物十八烷氧乙基替诺福韦酯(ODE-TFV)在体外及体内的抗乙型肝炎病毒的活性并研究其改善肝脏病理的作用.方法 分别以乙型肝炎病毒基因转染的人肝癌2.2.15细胞和DHBV感染的1日龄北京鸭为体外和体内模型,评价ODE-TFV抑制乙型肝炎病毒复制的活性.结果 2.2.15细胞培养法实验结果显示,ODE-TFV抑制HBV DNA复制的IC50值为(0.38±0.18)μmol/L,抑制活性较阳性药TFV-DF和3TC分别强约18倍和13倍;ODE-TFV 100 mg/kg和200 mg/kg组,在给药7d和停药3d显示有显著性的DHBV-DNA抑制活性(P＜ 0.01、P＜0.05);在鸭体内模型中,ODE-TFV 100 mg/kg和200 mg/kg能够明显改善DHBV引起的肝细胞坏死和炎细胞浸润,有一定量效关系.结论 ODE-TFV不仅在2.2.15细胞内对HBV-DNA有抑制活性,而且能有效地抑制鸭体内DHBV-DNA的复制,并具有改善肝脏病理的作用.     

磷甲酸钠在鸭体内对鸭乙型肝炎病毒的抑制作用

以鸭乙型肝炎病毒（ＤＨＢＶ）静脉感染雏鸭为模型,分组腹腔注射磷甲酸钠（ＰＦＡ）２５０ｍｇ、１２５ｍｇ、６２．５ｍｇ／ｋｇ及生理盐水,观察治疗后鸭血清中ＤＨＢＶＤＮＡ及ＤＨＢｓＡｇ的动态变化,并检测肝、肾、脾及胰中ＤＨＢＶＤＮＡ的分布;提取肝脏中超螺旋ＤＮＡ（ＳＣＤＮＡ）,检测ＰＦＡ对ＤＨＢＶＤＮＡ复制的影响。结果表明：ＰＦＡ治疗第７天到第２１天,１２５ｍｇ和２５０ｍｇ／ｋｇ剂量组对ＤＨＢｓＡｇ有显著的抑制作用;１２５ｍｇ和２５０ｍｇ／ｋｇ剂量组治疗第１４、２１天对血清中ＤＨＢＶＤＮＡ有显著的抑制作用;１２５ｍｇ和２５０ｍｇ／ｋｇ剂量组治疗第２１天肝及肾中ＤＨＢＶＤＮＡ明显下降;２５０ｍｇ／ｋｇ剂量组治疗２１天对ＤＨＢＶ感染鸭肝细胞内ＤＨＢＶＲＣＤＮＡ、ＬＤＮＡ及ＳＣＤＮＡ的合成有明显抑制作用。可见,最大剂量２５０ｍｇ／ｋｇＰＦＡ每天２次,治疗２１天,对ＤＨＢＶ感染鸭血清中ＤＨＢｓＡｇ、血清及肝、肾中ＤＨＢＶＤＮＡ都有抑制作用,对脾、胰中ＤＨＢＶＤＮＡ抑制不明显。提示该药能抑制ＤＨＢＶ感染,但未能清除病毒,故停药后可出现反跳现象。     

A study of duck hepatitis B virus infection in Chinese ducklings]

Intraperitoneal inoculation of duck hepatitis B virus in three different dosages (9 x 10(7), 1.8 x 10(8), 9 x 10(8) DHBV particles) into 3 to 21 day-old Chinese ducklings provided from a DHBV free flock produced a persistent infection up to 93.3% in 60 animals. The serum and liver specimens of these ducklings were examined by DNA dot blot hybridization on the 30th day after inoculation. The results showed that: (1) examination of viral DNA in liver was more sensitive and reliable than estimation of the DNA in serum for detecting DHBV infection in inoculated ducklings; (2) the liver DHBV DNA level did not coincide with the degree of liver hepatitis induced; (3) 21-day-old Chinese ducklings were also susceptible to DHBV infection, the infection rate of this group was 100% (10/10).     

Effects of purine nucleoside analogues with a cyclobutane ring and erythromycin A oxime derivatives on duck hepatitis B virus replication in vivo and in cell culture and HIV-1 in cell culture.

The effects on duck hepatitis B virus (DHBV) replication of specific analogues of two classes of chemical compounds not previously tested against hepadnaviruses are described. One is erythromycin A-9-methyloxime (EMO) and other oxime derivatives of erythromycin A, and the other is purine nucleoside analogues (cyclobut A and cyclobut G) with cyclobutane rings. Viral replication was assessed by measuring serum levels of DHBV DNA in infected ducklings and DHBV DNA in infected primary duck hepatocyte cultures. Administration of EMO 15 mg/kg of body weight IM to infected ducklings resulted in a rapid fall in DHBV DNA levels during therapy and a return to pretreatment levels after EMO administration was stopped. There was local toxicity at injection sites with muscle necrosis in some animals. When 100 mg/kg EMO was administered by gastric tube no such viral response was observed. The difference in virus response to EMO 15mg/kg IM and 100 mg/kg by gastric tube was not due to failure to achieve comparable blood and tissue levels of EMO administered by the different routes. The results suggest an indirect effect dependent on IM injection of EMO rather than a direct antiviral effect of the compound. Administration of cyclobut G or cyclobut A at 70 mg/kg IM led to a rapid reduction of DHBV DNA to undetectable levels in serum, and in only 1 of 4 animals did DHBV DNA became detectable again within 10 days after stopping the drug.(ABSTRACT TRUNCATED AT 250 WORDS)     

Comparative study of DHBV DNA levels and endogenous DNA polymerase activity in naturally infected ducklings in France

Duck hepatitis B virus (DHBV) was found in the serum of 1-6% of Pekin ducklings originated from French commercial flocks. The viremia was followed in the serum of 5 ducklings over a span of 3 mth by monitoring the levels of DHBV DNA and the endogenous DNA polymerase (DNAp) activity. The DHBV DNA levels in serum were quantified either by the DNA dot hybridization technique including counting of retained radioactivity, or by successive dilutions of each serum sample followed by DNA hybridization. The counting of the retained radioactivity was plotted on a curve and its evolution compared with that of viral DNAp activity. DHBV DNA levels in serum, estimated by both methods paralleled those of the DNAp activity, which peaked at the 4th or 5th week posthatch to decrease and fluctuate thereafter. Occasional discordance between DHBV DNA levels and the endogenous DNAp activity was observed, which could be correlated with the degree of repair of the single stranded gap of serum DHBV DNA. Parallel follow up studies comparing quantitative estimations of serum viral DNA and of DNAp activity, as presented here, may provide some clues for the understanding of the mechanisms involved in the establishment of the HEPA DNA virus carrier state. Such comparative studies may also be crucial for optimal monitoring of antiviral drugs in both human clinical trials and animal experimental studies.     

Evaluation of Phyllanthus amarus and Phyllanthus maderaspatensis as agents for postexposure prophylaxis in neonatal duck hepatitis B virus infection

The therapeutic potential of plant extracts of Phyllanthus amarus and Phyllanthus maderaspatensis for postexposure prophylaxis against infection by Hepadnaviruses was studied in ducklings infected by the duck hepatitis B virus (DHBV). Forty-four Pekin ducklings were inoculated intraperitoneally with DHBV at 24 hr posthatch. They were treated by intraperitoneal injection of Phyllanthus amarus (aqueous extract) (100 mg/kg body weight) or Phyllanthus mad eraspatensis (alcoholic extract) (100 mg/kg body weight) for a period of 4 weeks. Infected ducklings treated with saline served as controls. Weekly serum samples obtained before, during, and after treatment were analysed for the presence of DHBV DNA in serum by dot blot hybridisation using α ³²P-labelled probes. Liver tissue was collected after killing the ducks at various time intervals and was studied for replicative status of the viral DNA and liver histopathology; 17 of 21 ducks were viraemic on completion of treatment with Phyllanthus amarus. At 16 week posttreatment follow-up four of seven animals remained viraemic. Similar results were obtained with Phyllanthus maderaspatensis. There was no alteration in DHBV replication in the liver. No toxicity was observed with this treatment. These observations suggest that Phyllanthus amarus and Phyllanthus maderaspatensis are not useful as therapeutic agents for postexposure prophylaxis against DHBV infection. © 1993 Wiley-Liss, Inc.     

Oral famciclovir against duck hepatitis B virus replication in hepatic and nonhepatic tissues of ducklings infected in ovo

Detection of hepadnaviral DMA in extrahepatic tissues of human and animal models of hepatitis B virus (HBV) has raised the question of whether virus replication in organs other than the liver could be targeted for the treatment of chronic hepatitis B. Since duck hepatitis B virus (DHBV) replication is dynamic in the liver, kidney, pancreas, and spleen of newly hatched ducklings infected in ovo, we used the duck model and the new antiherpesvirus agent, famciclovir (FCV), to determine whether antiviral effect of nucleoside analogues on DHBV replication is pluripotential. Day-old ducklings hatched from eggs laid by a DHBV-carrier duck were bled and administered FCV (25 mg/kg/bd) orally for periods of 1, 2, 3, 6, 9, and 12 days. Seventeen (17) hours after the last dose of each regimen the duckling(s) was bled and postmortem samples of liver, kidney, pancreas, and spleen were snap-frozen and stored at ?70°. Analysis of plasma samples of ducklings treated for 2 days and longer by dot-blot hybridisation showed that levels of DHBV DNA were reduced significantly compared to levels in samples collected before treatment begun. Southern blot hybridisation of tissue DNA corroborated these results and showed that DHBV DNA replicative intermediates in all the tissues examined were reduced to levels that reflected the amount of virus released into the blood of each treated duckling. It is concluded from these results that if antiviral agents could be transformed to active metabolites in any infected tissues including the liver, replication of hepadnaviruses would be inhibited. We also note that the ability of young ducklings to metabolise FCV to the parent compound, penciclovir, suggests that hatchlings could be used for screening antiviral compounds under development. © 1994 Wiley-Liss, Inc.     

反义寡脱氧核苷酸在鸭体内抑制鸭乙型肝炎病毒复制与 …

目的 研究反义核酸的抗病毒作用。方法 设计合成了针对鸭乙型肝炎病毒（ＤＨＢＶ）前Ｓ（ＰｒｅＳ）基因区第９５１－９６８位核苷酸的硫代反义寡脱氧核苷酸（ＡＳ－ＯＤＮ），以２０μｇ／ｇ体重／日剂量对３只腹腔感染ＤＨＢＶ５．２毒株后，血清ＤＨＢｓＡｇ及ＤＨＢＶ ＤＮＡ阳性鸭连续静脉注射１０天，同时以等体积生理盐水注射另３只感染鸭作为对照。结果 对照鸭注射生理盐水后，血清ＤＨＢｓＡｇ及ＤＨＢＶ ＤＮＡ阳性未