血管胶原代射改变及其在大鼠低氧性肺动脉高压形成中的作用

测定了低氧性肺动脉高压大鼠肺动脉羟脯氨酸含量，可溶性Ⅰ／Ⅲ型胶原比值及肺血管顺应性。发现随低氧时间的延长，ＨＰ增加越多。而胸主动脉中ＨＰ含量无明显改变。低氧２１天时所测定的可溶性Ⅰ／Ⅲ型胶原比值显著升高。低氧１４，２１天时肺血管顺应性显著下降。复常氧一段时间后升高的ＰＡＰ及ＨＰ含量可自然恢复。７６４－３处理可部分阻止低氧所致的上述变化。提示肺血管中胶原，特别是Ⅰ型胶原合成增多在维护肺动脉高压中起重     

胶原代谢变化在大鼠低氧性肺动脉高压发病学中的作用及其可逆性

实验用雄性Wistar大鼠,分对照组(C)、单纯低氧组(Hy)及每天皮下注入764-3(50mg/kgBW)处理低氧组(764-3+Hy)。动态观察了常压低氧大鼠肺动脉压(PAP)、肺动脉中羟脯氨酸(HP)含量的变化及形成肺动脉高压时肺血管中Ⅰ/Ⅲ型胶原比值和肺血管顺应性.每组各时间点为9～12只大鼠.发现Hy组PAP明显高于对照组,低氧3、7、14、21天时(以下均按此顺序)C组与Hy组PAP分别为2.65±0.12、2.59±0.10、2.59±0.10、2.76±0.11kPa(X±SE,下同)及3.09±0.20、3.43±0.19、3.52±0.11、3.62±0.12Pa(与对照组比P<0.05,P<0.01,下同).764-3可明显缓解低氧性肺动脉高压,PAP     

低氧性动脉高压大鼠肺动脉壁Ⅰ,Ⅲ型胶原及其mRNA的变化

用双醋酸－－胃蛋白消化法提取可溶性Ⅰ、Ⅲ型胶原混俣物，用β－巯基乙醇阻断－ＳＤＳ－ＰＡＧＥ分出Ⅲ型胶原之单α１（Ⅲ）条带测定常压低氧大鼠肺外肺动脉中Ⅰ、Ⅲ胶原比例的变化。结果表明，吸入低氧气体１周／Ⅲ型胶原比值未见有统计学意义的变化；吸入低氧气体３周、Ⅲ型胶原比值明显升高。崦在吸入低氧气体１周时Ｉ型前胶原ｍＲＮＡ已呈有统计学意义之升高。     

内源性一氧化碳对低氧大鼠肺动脉胶原代谢的影响

探讨内源性一氧化碳 (CO)对低氧大鼠肺动脉胶原代谢的作用及其机制。采用常压低氧大鼠肺动脉高压模型 ,观察血红素加氧酶 (HO)抑制剂锌原卟啉 9(ZnPP 9)对肺动脉平均压 (PAMP)和肺组织匀浆碳氧血红蛋白 (Hb CO)含量的影响 ,并用免疫组织化学和核酸原位杂交法分别观察Ⅰ、Ⅲ型胶原蛋白的表达和肺动脉Ⅲ型前胶原[Proα1 (Ⅲ )胶原 ]mRNA、间质性胶原酶 (MMP 1)mRNA、金属蛋白酶组织抑制因子 1(TIMP)mRNA表达的变化。结果发现ZnPP 9使低氧大鼠PAMP明显升高 ,肺组织匀浆CO含量明显降低 ;ZnPP 9显著促进低氧大鼠肺动脉Ⅰ、Ⅲ型胶原蛋白表达 (P <0 0 1)和Proα1 (Ⅲ )胶原mRNA表达及MMP 1mRNA与TIMP 1mRNA表达 (P <0 0 1)。内源性CO可能通过抑制胶原蛋白的合成对低氧大鼠肺动脉胶原代谢发挥重要的调节作用。     

慢性低氧对大鼠肺外肺动脉胶原基因表达的影响

复制常压低氧性肺动脉高压大鼠模型。测定肺动脉压、右心室收缩压及右心室重，用分子杂交法测定肺动脉、胸主动脉及右心室前胶原Ⅰ、Ⅲ型ｍＲＮＡ表达水平的变化和７６４－３处理对其影响。结果发现，低氧７天时肺动脉压、右心室收缩压及右心室重量显著增加。斑点印迹杂交分析显示肺外肺动脉中前胶原Ｉ型ｍＲＮＡ表达水平显著增加。７６４－３处理可显著缓解上述变化。肺动脉中前胶原Ⅲ型ｍＲＮＡ表达水平各组间无明显差异。胸主动脉     

Losartan对慢性低氧大鼠肺动脉压力及管壁胶原的影响

目的：探讨氯沙坦（losartan）对慢性低氧大鼠肺动脉压力及管壁胶原的影响。方法：将二级SD大鼠分为：对照组（A）、低氧组（B）、低氧+losartan组（C），低氧时间为4周。采用透射电镜、免疫组化、原位杂交等方法观察losartan对慢性低氧大鼠肺动脉平均压（mPAP）、右心室重量比（RV/LV+S）、肺细小动脉超微结构、肺动脉管壁Ⅰ、Ⅲ胶原和Ⅰ、Ⅲ前胶原基因的影响。结果：①B组mPAP、RV/LV+S显著高于A组（P<0.01），C组mPAP、RV/LV+S显著低于B组（P<0.01）。②电镜检查显示B组肺动脉胶原纤维较A组明显为多，C组较B组明显为少。③免疫组化、原位杂交显示B组肺细小动脉(直径约100-200μm)Ⅰ型胶原及Ⅰ型前胶原mRNA平均吸光度值显著高于A组（均P<0.01），C组肺细小动脉Ⅰ型胶原及Ⅰ型前胶原mRNA平均吸光度值明显低于B组（均P<0.01），Ⅲ型胶原及Ⅲ型前胶原mRNA平均吸光度值各组间无明显差异（均P>0.05）。结论：losartan可预防慢性低氧肺动脉高压的形成和肺动脉管壁胶原的生成、沉积。     

低氧性肺动脉高压大鼠肺动脉壁Ⅰ、Ⅲ型胶原及其mRNA的变化

用双醋酸－胃蛋白消化法提取可溶性１、Ⅲ型胶原混合物，用β－巯基乙醇阻断－ＳＤＳ－ＰＡＧＥ分出Ⅲ型胶原之单－α＿１（Ⅲ）条带测定常压低氧大鼠肺外肺动脉壁中1、Ⅲ胶原比值的变化。结果表明，吸入低氧气体１周Ｉ／Ⅲ型胶原比值未见有统计学意义的变化；吸入低氧气体３周Ｉ／Ⅲ型胶原比值明显升高。而在吸入低氧气体１周时Ｉ型前胶原［Ｐｒｏα＿１（Ｉ）］ｍＲＮＡ已呈有统计学意义之升高。     

764—3对大鼠低氧性肺动脉高压的作用

将大鼠置常压低氧舱(10％O_2～90％N_2)观察肺动脉压、右心室重及右心室功能的动态变化过程及764-3对其影响。低氧3天时除肺动脉压升高外上述其它指标无明显改变。自低氧7天时起,右心室重量及右心室功能也显著高于对照组,并持续至观察的21天。低氧21天后再吸常氧14天,上述变化基本恢复正常。764-3处理可显著缓解低氧所致的上述变化。结果提示低氧所致的变化在复氧后一定时期内可自然消退,764-3对低氧性肺动脉高压及右心室肥厚有明显的保护作用,作用机理有待进一步研究。     

中介素抑制高肺血流性肺动脉高压大鼠肺组织胶原生成

 目的:研究中介素（IMD）对高肺血流性肺动脉高压大鼠肺组织胶原生成和沉积的调节作用及其机制。方法: 健康雄性SD大鼠20只,随机分为对照组（n=7）、分流组（n=7）和分流+IMD组（n=6）。对后2组大鼠行腹主动脉-下腔静脉分流术。8周后,对分流+IMD组大鼠,皮下埋微量渗透泵持续给予IMD 1.5 μg·kg-1·h-1。继续饲养2周后,比较各组大鼠肺动脉平均压（mPAP）、肺中、小动脉相对中膜厚度（RMT）,肺组织羟脯氨酸、Ⅰ和Ⅲ 型胶原、骨形成蛋白-2（BMP-2）含量和I、III型前胶原mRNA表达水平。结果: 与对照组相比,分流组大鼠mPAP明显上升,肺中、小动脉RMT明显增加,肺组织羟脯氨酸和Ⅰ、Ⅲ型胶原含量明显增多,Ⅰ、Ⅲ型前胶原mRNA表达上调,BMP-2含量明显增多。IMD则使分流大鼠肺动脉压力明显回降,肺血管结构改变缓解,胶原沉积减少,BMP-2含量降低,Ⅰ、Ⅲ 型前胶原mRNA表达下调。结论: IMD可通过抑制高肺血流大鼠肺组织胶原生成和沉积,缓解高肺血流性肺动脉高压和肺血管结构重构形成,该作用可能与BMP-2途径有关。     

慢性肺动脉高压肺血管力学特性的评价

本文以风心病二尖瓣病变合并被动性肺动脉高压为研究对象,借助右心导管技术和利用压力波形面积确定动脉顺应性的改进方法,通过测定肺血管阻力和顺应性,以评价慢性肺动脉高压肺血管力学特性的变化规律。发现慢性肺动脉高压患者肺动脉血管阻力明显升高（P＜0.01）;而反映血管壁固有结构的零压顺应性Co明显下降(P＜0.01),与术前肺动脉平均压呈显著负相关(r＝－0.745P＜0.05);扩血管药物试验提示不同程度肺动脉高压组的肺血管阻力均有显著下降(P＜0.01),轻度肺高压组零压顺应性和平均压顺应性均明显升高(P＜0.01);而重度肺高压组零压顺应性Co无明显变化(P＞0.05)。由此我们认为慢性肺高压肺血管都存在不同程度的重建,肺血管外周血管阻力和顺应性是影响其肺动脉压力水平的主要因素。     

雷公藤甲素抗肿瘤血管新生的研究进展（英文）

雷公藤甲素(triptolide,TPL)是从中草药雷公藤中提取的一种有效活性物质,已被用来治疗多种疾病,包括系统性红斑狼疮,类风湿性关节炎,肾病综合征等,TPL甚至有很强的抑制肿瘤的活性。近些年的研究显示,TPL具有抗血管新生的能力,TPL不仅可以抑制肿瘤的增殖,诱导细胞的凋亡,还可以抑制肿瘤的转移,可以增加其它化疗药物的抗肿瘤活性。本综述将讨论TPL在抗肿瘤血管新生方面的研究进展,以及初步探讨其潜在的作用机制。     

Changes in activity of neutral proteases in tissues of ground squirrels in the dynamics of hibernation

Total activities of neutral proteases in the cerebral, hepatic, and myocardial tissues of ground squirrel vary during hibernation: in autumn (before hibernation) activities of the enzymes in the brain and myocardium start increasing, while in the liver they do not change. A common feature for all tissues is minimum activity of active neutral proteases in the middle of hibernation month 1 bout, while the maximum activity is recorded before awakening. Translated from Byulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 146, No. 9, pp. 278–280, September, 2008     

Kinetics of decline of maternal measles virus-neutralizing antibodies in sera of infants in France in 2006

The optimal age for measles vaccination is an important health issue, since maternal antibodies may neutralize the vaccine antigen before a specific immune response develops, while delaying vaccination may increase the risk of complicated diseases in infants. However, measles vaccination impacts the duration of protection afforded by transplacental transfer of maternal antibodies: vaccination-induced maternal antibodies disappear faster than disease-induced antibodies. In order to maintain protection against measles in infants, it is important to monitor the dynamics of this phenomenon in vaccinated populations. To assess the current situation in France, a multicenter, prospective seroepidemiological study was conducted in seven French hospitals between October 2005 and January 2007. Maternal measles antibody concentrations from 348 infants 0 to 15 months old were measured using the plaque reduction neutralization assay. Geometric mean concentrations and the percentage of infants with maternal measles antibody concentrations above the protection threshold (≥120 mIU/ml) were assessed according to age. Results show that after more than 20 years of routine measles vaccination in France, maternal measles-neutralizing antibodies decrease dramatically in French infants by 6 months of age, from 1,740 mIU/ml for infants 0 to 1 month old to 223 mIU/ml for infants 5 to 6 months old, and that 90% of infants are not protected against measles after 6 months of age. Infant protection against measles could be optimized both by increasing herd immunity through an increased vaccine coverage and by lowering the age of routine vaccination from 12 to 9 months.     

MiRNA调控肿瘤细胞中P-gP表达的研究进展

微小RNA（miRNA）是一类高度保守的非编码单链RNA分子,与靶基因mRNA3’端非编码区结合,抑制mRNA的翻译,促进靶基因降解。而这种调控机制与很多肿瘤细胞中P型糖蛋白（P,glycoprotein,p-gp）的表达有着密切的联系。p-gp是与耐药相关的跨膜蛋白,过表达可导致肿瘤细胞产生多药耐药（multidrugresistance,MDR）。就miRNA的生物学特性、p-gP的功能进行综述,关系。肿瘤MDR是临床化学治疗失败的主要原因,本文并重点介绍其调控肿瘤细胞中P-gP表达和MDR的     

Molecular Characterization of Bacillus Strains Involved in Outbreaks of Anthrax in France in 1997

Outbreaks of anthrax zoonose occurred in two regions of France in 1997. Ninety-four animals died, and there were three nonfatal cases in humans. The diagnosis of anthrax was rapidly confirmed by bacteriological and molecular biological methods. The strains of Bacillus anthracis in animal and soil samples were identified by a multiplex PCR assay. They all belonged to the variable-number tandem repeat (VNTR) group (VNTR)₃. A penicillin-resistant strain was detected. Nonvirulent bacilli related to B. anthracis, of all VNTR types, were also found in the soil.