胺碘酮、美托洛尔对家免急性心肌梗死血小板活化、纤溶活性、内皮血管活性物质的影响

目的：探讨胺碘酮、美托洛尔对兔急性心肌梗死(AMI)血小板活化、纤溶活性、内皮血管活性物质的影响。方法：新西兰家兔50只，随机分为5组，每组10只。I组：假手术组，Ⅱ组：AMI组，Ⅲ组：AMI 利多卡因组，Ⅳ组：AMT 胺碘酮组，Ⅴ组：AMI 美托洛尔组；Ⅱ、Ⅲ、Ⅳ、Ⅴ组分别结扎冠状动脉左室支中点后，4h取血分别测定血栓素B2(TXB2)、6—酮—前列腺素F1a(6—Keto—PGF1a)、内皮素(ET)、一氧化氮(NO)和组织型纤溶酶原激活剂(t—PA)、纤溶酶原微活剂抑制物(PAI)水平；摘取心脏，测定心肌梗死范围。结果：Ⅱ、Ⅲ、Ⅳ、Ⅴ组血浆TXB2、ET、NO浓度和则活性显著高于I组(P＜0．01)，6—Keto—PGF1a浓度和t—PA活性显著低于I组(P＜0．01)，Ⅱ、Ⅲ、Ⅳ组之间比较，血浆TXB2、6—Keto—PGF1a。浓度、t—PA活性及心肌梗塞范围无显著差异(P＞0．05)，Ⅳ组血浆ET、NO浓度和PAI水平明显低于Ⅱ组（P＜0．01)，Ⅴ组血浆TXB2、ET、NO浓度和PAI水平明显低于Ⅱ组(P＜0．01)，6—Keto—PGF1Aa。浓度、t—PA活性显著高于Ⅱ组(P＜0．01)，心肌梗塞范围小于Ⅱ组(P＜0．01)。结论：胺碘抑制AMI早期PAI活性，减少ET和NO的释放；美托洛尔抑制AMI早期血小板活化，改善纤溶活性，减少ET和NO的再释放，缩小心肌梗塞范围。利多卡因无上述作用。     

β-受体阻滞剂对家兔心肌缺血再灌注后纤溶活性及血管活性物质含量的影响

探讨艾司洛尔、索他洛尔、美托洛尔和卡维地洛对家兔心肌缺血再灌注后纤溶活性、血管内皮活性物质含量的影响。新西兰大白兔 5 8只 ,随机分为 6组 ,Ⅰ组 :AMI组 ,Ⅱ组 :缺血 再灌注 (ischemicreperfusion ,IR)组 ,Ⅲ组 :IR +艾司洛尔组 ,Ⅳ组 :IR +索他洛尔组 ,Ⅴ组 :IR +美托洛尔组 ,Ⅵ组 :IR +卡维地洛组 ;制作IR动物模型 (除AMI组 ) ,缺血 6 0min后再灌注 2 4 0min ,分别于缺血前、再灌注前 ,再灌注 2 4 0min后取血测定t PA、PAI 1的活性和ET、NO浓度。结果显示 :冠脉结扎后 ,血浆ET、NO浓度和PAI 1活性显著高于结扎前 ,而t PA活性显著低于结扎前 (P <0 0 1) ,再灌注后 ,血浆ET、NO浓度和PAI 1活性进一步升高 ,t PA活性进一步下降 (P <0 0 1)。与IR组对比 ,各组NO的浓度再灌注后无显著性差异 ,艾司洛尔组再灌注后血ET浓度显著降低 (P <0 0 1) ,血t PA、PAI 1活性无明显的变化 ;索他洛尔、美托洛尔、卡维地洛均能显著的升高再灌注后t PA活性 ,降低血PAI 1活性和ET浓度 (P <0 0 1)。提示 :索他洛尔、美托洛尔、卡维地洛有改善缺血再灌注过程中纤溶活性、抑制内皮细胞释放ET的有益作用 ;艾司洛尔能抑制缺血再灌注过程中ET的释放 ,对纤溶活性无明显的影响     

冠心病患者血浆ET、TXB2、6-Keto-PGF1α的观察

目的：探讨血浆内皮素（ET）、血栓素（TXB2）、6-酮-前列腺素1α（6-Keto-PGF1α）在冠心病患者发病中的变化及临床意义。方法：放射免疫分析测定25例不稳定型心绞痛（UA）：22例急性心肌梗死（AMI）和35例正常对照血浆。结果：三组年龄对比无显著性差异（P〉0．05），UA组心绞痛发作期与终止期比较及AMI组溶栓前与溶栓后比较有显著性差异（P〈0.01）。结论：ET的过度分泌加剧了血小板的激活，导致TXB2／6-Keto-PGF1α比例失调；三者共同参与冠状动脉痉挛和血栓形成过程；短时间内ET的过度分泌与TXB2／6-Keto-PGF1α代谢失调促进与加强加速了UA向AMI的转化。     

高血压病各期纤溶活性变化的意义

进一步探讨高血压病各期纤溶活性变化的临床意义 ,为早期防治寻找依据。方法用发色底物法测定血浆纤溶酶原激活物抑制物(PAI)、组织型纤溶酶原激活物(t-PA)及纤溶酶原(PLG)的含量。结果①高血压病Ⅱ期、急性脑梗塞及脑出血各项指标均与正常组比较有明显差异(P<0.001) ,急性脑出血、脑梗塞较高血压病Ⅱ期t-PA、PAI有明显差异(P<0.01);②脑卒中各组纤溶活性均无明显差异(P>0.05) ;③合并冠心病者与单纯高血压病Ⅱ期比较 ,t -PA、PAI有明显差异(P<0.01)。结论高血压病各期存在纤溶功能的失衡 ,提示早期干预治疗的重要性。测定血浆PAI、t-PA ,有利于判断高血压病的严重程度、疗效、预后     

卡托普利和地尔硫卓对犬急性心肌缺血溶栓治疗的影响

目的观察卡托普利和地尔硫卓对犬急性心肌梗死溶栓再灌注心肌损伤和纤溶凝血系统的影响。方法建立犬急性心肌缺血溶栓治疗的模型,溶栓同时应用卡托普利和地尔硫卓药物干预,测定治疗过程中组织型纤溶酶原激活物(t-PA)、组织型纤溶酶原抑制物(PAI)、血栓素(TXB2)、前列环素(6-酮-PGF1a)的含量和心肌酶谱等的动态变化。结果溶栓加用卡托普利治疗后,心肌损伤进一步减轻。溶栓后期t-PA活性无明显下降,PAI活性进一步减低,血浆TXB2均值降低,PGI2均值上升。溶栓加用地尔硫卓:血浆TXB2均值降低,PGI2均值上升。结论溶栓治疗时应用卡托普利可使再灌注心肌损伤进一步减轻,心肌梗死面积和范围减小;可以进一步改善纤溶-凝血功能障碍,升高t-PA和PGI2,降低PAI和TXB2,防治血栓形成对心肌缺血的进一步损害。地尔硫卓可以调节再灌注后PGI2/TXB2失衡,升高PGI2,降低TXB2,减轻血管痉挛和血栓形成,改善心肌缺血。     

冠心病人止凝血分子标志物指标异常的研究

目的探讨冠心病人发病早期止凝血系统的变化及血栓形成的原因、发生机制与临床意义。方法采用发色底物法(t-PA、PAI活性) ,Laurell免疫火箭电泳法(vWF∶Ag、AT-Ⅲ含量) ,凝血酶空斑法(AT -Ⅲ∶C)对冠心病人组及正常对照组进行检测。结果冠心病患者与正常人对照组比较 :AMI组与正常对照组比较t-PA、PAI、vWF∶Ag、AT-Ⅲ∶C、AT-Ⅲ∶Ag均有极显著性差异(P<0 .001)。UA组与正常对照组比较vWF∶Ag、AT-Ⅲ∶C有显著性差异(P<0.05) ,而t-PA、PAI、AT-Ⅲ∶Ag无显著性差异。AMI与UA组比较t-PA、PAI、AT-Ⅲ∶Ag有极显著性差异(P<0 .01) ,vWF∶Ag、AT -Ⅲ∶C无显著性差异。结论AMI有纤溶系统抑制 ,凝血系统功能亢进等多因素异常。而UA是凝血系统功能亢进、纤溶系统变化不明显 ,这可能与冠心病的病情发展和严重程度有关。     

脑梗塞患者甘油三脂与纤溶活性异常的研究

目的 :探讨脑梗塞患者血高甘油三酯与纤溶系统异常的危险因素。方法 :采用酶联免疫吸附双抗体夹心法、酶法 ,对 5 1例脑梗塞患者及 5 0例健康对照组血组织型纤溶酶原激活物 (t PA) ,纤溶酶原激活物抑制物 1(PAI 1)和甘油三酯 (TG)水平进行了对比分析。结果 :血高TG、高PAI 1,与低t PA含量变化为脑梗塞患者异常变化特征 ,与正常组相比有显著性差异 (P <0 .0 1)。结论 :高甘油三酯通过改变纤溶活性是诱发脑梗塞疾病发生、发展的危险生物学因素     

溶栓治疗对急性心肌梗塞患者纤溶系统功能的影响

本文通过观察纤溶系统活性,纤维蛋白原(Fg)、纤维蛋白降解产物(FDP)含量变化,探讨蛇毒抗栓酶(SVATE)、UK溶栓治疗对急性心肌梗塞(AMI)的临床意义。结果表明,静脉一次大剂量UK治疗,患者血浆PL、ELA、t-PA活性和FDP出现快速大幅度增高,PAI、Fg降低、这种作用仅持续短时间、SVATE静脉首次大剂量以后小剂量维持2周处理,血浆上述纤溶指标逐渐恢复,ELA、t-PA和PAI活性2～3周接近正常水平。结果提示,SVATE、UK溶栓治疗使AMI患者纤溶功能得到改善,若采用二者联合用药,效果可能更理想。     

实验性心肌梗塞大鼠冠脉等组织纤溶因子表达的变化

通过观察大鼠实验性急性心肌梗塞（AMI）时，冠状动脉及周围心肌组织组织型纤溶酶原激活剂（t－PA），及其特异性抑制因子（PAI－1）基因表达及t－PA活性变化，从纤洛因子失衡方面探讨AMI发病机理，并研究缺血预处理调整纤溶功能的保护作用。结果表明，缺血和缺血再灌时组织t－PA活性均显著降低（P＜0．01），经预处理的缺血心肌t－PA活性有所升高（与缺血组相比P＜0．01）。AMI时t－PA、PAI－1表达均呈高水平，分别为对照组的1．19信和4．59倍而预处理组表达减弱。说明t－PA、PAI－1失衡参与AMI发展过程，缺血预处理对心肌的保护可能与纠正上述纤溶因子失衡有关。     

甲基强的松龙对狼疮性肾炎患者血浆中PAI-1的影响

目的 :研究甲基强的松龙对Ⅳ型狼疮性肾炎 (LN)患者血浆中 1型纤溶酶原激活物抑制物 (PAI 1)的影响。方法 :应用免疫组织化学ELISA方法检测患者血浆中PAI 1含量。结果 :①LN治疗组与对照组比较 (P <0 0 1) ;②LN患者经甲基强的松龙两次冲击治疗后与治疗前分别比较 (P <0 .0 1) ;③甲基强的松龙第二次冲击治疗后 ,与对照组比较无显著性差异 (P >0 0 5 )。结论 :甲基强的松龙通过干扰纤溶酶原激活物 (PA) 纤溶酶系统 ,使LN病人血浆中PAI 1含量明显降低 ,从而发挥治疗作用。     

Economical and rational in vivo and in vitro diagnosis in Basedow hyperthyroidism

Immunogenic hyperthyroidism (Graves' disease) is a life-long ailment. A widespread diagnostic evaluation is essential for unbiased initial values prior to therapy. The major goals of initial investigation are to determine a functional disturbance of the organ, its pathogenesis and morphology. Even a suppressed ultrasensitive bTSH value represents no evidence of overt hyperthyroidism; a positive diagnosis can only be established by the additional presence of increased parameters of circulating free thyroid hormones (fT3, fT4). Evidence of any immunogenic pathogenesis is given by positive thyroid antibody values (TRAK, MAK, TAK). Moreover, the use of sonography (with poor diffuse echo and increased thyroid depth) as well as Tc-99m scan indicating primary autonomy, thyroxine induced hyperthyroidism or painless thyroiditis) may both prove rather useful in a rational and economical diagnosis of Graves' disease.     

The cyclic-AMP concentration in plasma and in muscle in response to exercise and beta-blockade in man

At rest the cAMP concentration in (muscle samples of) the quadriceps femoris ranged from 1.55 to 3.00 μmol per kg dry muscle and in plasma from 15.3 to 32.3 nmol per 1. Blockade of the beta adrenoreceptors with propranolol resulted in a significant decrease in the concentration in muscle at rest, the magnitude of the fall being related to the inital level. Similarly in plasma there was a trend towards lower levels of cAMP in those with the highest pretreatment levels, but the overall change was not statistically significant. There was no relation between the concentrations in muscle and plasma, before or after beta-blockade. Maximum dynamic exercise for 4–8 min resulted in an approximate doubling in the cAMP concentration in both muscle and blood. The increase in plasma was closely related to that in muscle. Beta-blockade inhibited totally the rise in cAMP in muscle during exercise but was marginally less effective in preventing the increase in blood. No increase in plasma or muscle cAMP levels during 40–70 s isometric contraction were observed.     

Age-related impairments in memory and in CREB and pCREB expression in hippocampus and amygdala following inhibitory avoidance training

This experiment examined whether age-related changes in CREB and pCREB contribute to the rapid forgetting seen in aged animals. Young (3-month-old) and aged (24-month-old) Fischer-344 rats received inhibitory avoidance training with a low (0.2 mA, 0.4 s) or moderate (0.5 mA, 0.5 s) foot shock; memory was measured 7 days later. Other rats were euthanized 30 min after training, and CREB and pCREB expression levels were examined in the hippocampus, amygdala, and piriform cortex using immunohistochemistry. CREB levels decreased with age in the hippocampus and amygdala. After training with either shock level, young rats exhibited good memory and increases in pCREB levels in the hippocampus and amygdala. Aged rats exhibited good memory for the moderate but not the low shock but did not show increases in pCREB levels after either shock intensity. These results suggest that decreases in total CREB and in pCREB activation in the hippocampus and amygdala may contribute to rapid forgetting in aged rats. After moderate foot shock, the stable memory in old rats together with absence of CREB activation suggests either that CREB was phosphorylated in a spatiotemporal pattern other than analyzed here or that the stronger training conditions engaged alternate mechanisms that promote long-lasting memory.     

Ceramide in apoptosis and oxidative stress in allergic inflammation and asthma

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ALA和HMME水凝胶栓剂的制备和体内外释药研究

目的 制备光敏剂5-氨基酮戊酸(ALA)和血卟啉单甲醚(HMME)水凝胶栓剂,评价其对直肠肿瘤组织的光敏剂递送效率.方法 将皮下移植人直肠癌细胞SW837的BALB/c小鼠随机分为水凝胶栓剂直肠局部给药组、皮肤局部给药组、瘤内注射给药组和静脉注射给药组.用荧光光谱仪测量直肠壁、皮肤和皮下肿瘤中原卟啉(PpⅨ)和HMME的浓度,荧光光谱系统测定相应的光敏剂分布情况.结果 ALA水凝胶栓剂直肠局部给药组的PpⅨ浓度分别是皮肤局部给药组的9.76倍(1 h)和5.80倍(3 h),差异均具有统计学意义(均P＜0.05).皮肤局部给药后2h,ALA在肿瘤组织内达到最大穿透深度(3～6 mm).而HMME水凝胶栓剂直肠局部给药后,直肠壁中的HMME浓度极低,且皮肤局部给药后的最大肿瘤穿透深度不足2 mm.结论 与皮肤相比,ALA更易穿透黏膜屏障,以水凝胶栓剂形式直肠局部给药有望成为ALA用于光动力疗法治疗直肠癌的一种给药方式.     

Imaging beta-cell mass and function in situ and in vivo

Glucose-stimulated insulin secretion (GSIS) from pancreatic beta-cells is critical to the maintenance of blood glucose homeostasis in animals. Both decrease in pancreatic beta-cell mass and defects in beta-cell function contribute to the onset of diabetes, although the underlying mechanisms remain largely unknown. Molecular imaging techniques can help beta-cell study in a number of ways. High-resolution fluorescence imaging techniques provide novel insights into the fundamental mechanisms underlying GSIS in isolated beta-cells or in situ in pancreatic islets, and dynamic changes of beta-cell mass and function can be noninvasively monitored in vivo by imaging techniques such as positron emission tomography and single-photon emission computed tomography. All these techniques will contribute to the better understanding of the progression of diabetes and the search for the optimized therapeutic measures that reverse deficits in beta-cell mass and function.