远端缺血预处理在成人瓣膜置换术中的心肌保护作用

目的 评估远端缺血预处理在成人瓣膜置换术中的心肌保护作用.方法 随机选取40例风湿性心脏病需行瓣膜置换术的患者,分为远端预处理组和对照组,每组20例.分别于麻醉诱导前（T0）、停机时（T1）、停机后6小时（T2）和停机后24小时（T3）各时点抽取静脉血,测定血清肌钙蛋白I（cTnI）、乳酸脱氢酶（LDH）、超氧化物歧化酶（SOD）、丙二醛（MDA）、肿瘤坏死因子α（TNF-α）、白介素1β（IL-1β）的浓度.结果 远端预处理组T1、T2、T3的cTnI、LDH、TNF-α、IL-1β浓度均显著低于对照组,差异有统计学意义（P〈0.05）,T2、T3的MDA浓度明显低于对照组,SOD浓度明显高于对照组,差异具有统计学意义（P〈0.05）.结论 远端缺血预处理可减轻心肌缺血再灌注损伤,促进保护性炎性因子的分泌,有助于缺血再灌注后心功能的恢复及改善.     

单克隆抗体在缺血再灌注损伤中的心肌保护作用

细胞粘附蛋白可介导中性粒细胞与内皮细胞的相互作用,引起内皮细胞功能不良,导致缺血再灌注损伤。实验证明,应用某些单克隆抗体可抑制这些粘附分子的作用,从而提高心脏对缺血再灌注损伤的耐受性,使心脏手术更安全。     

洛伐他汀预适应在大鼠急性缺血再灌注中的心肌保护作用

目的:探讨洛伐他汀预适应对大鼠心脏急性缺血再灌注中的心肌保护作用及其机制。方法:将 24只SD大鼠随机分为3组(每组均8只):模型对照组(C组); 洛伐他汀组( L组),胃管直接灌注洛伐他汀 15 mg·kg-1·d-12周;洛伐他汀复合L 硝基精氨酸甲酯(L NAME)组(N组),洛伐他汀直接灌胃 2 周同时腹腔注射L NAME 30 mg·kg-1·d-1;2周后建立体内急性缺血再灌注心脏模型,监测缺血再灌注前后血流动力学各项指标,同时观察各组血脂水平及其血浆中丙二醛(MDA) 、心肌组织内超氧化物歧化酶(SOD)变化情况。结果: L组和N组较C组心率明显变慢(P<0.01),缺血再灌注心律失常消失和再灌注时-dp/dtmax下降明显改善(P<0.05);同时各项血脂指标不变,洛伐他汀能明显减少再灌注时血浆中MDA生成, 并且提高心肌组织SOD活性(P<0.05)。结论:洛伐他汀预适应对体内大鼠心脏急性缺血再灌注时具有非降脂外的心肌保护作用,其机制除与其增加一氧化氮(NO)合成相关外,可能还有其他物质或途径参与。     

缝隙连接蛋白43在缺血预处理心肌保护机制中的作用

缺血预处理是迄今发现的最强大的心肌内源性保护措施,很多研究对其机制作了深入、广泛的探讨,但目前为止,对缺血预处理心肌保护的确切机制还不能够被完全解释。近年来有研究发现缝隙连接蛋白43在缺血预处理心肌保护机制中也起着重要的调控作用,本文将从缝隙连接蛋白43的结构、分布、功能,以及心肌缺血与缺血预处理对缝隙连接蛋白43表达及功能的影响作一综述。     

缺血预处理和后处理联合应用在心肌缺血再灌注损伤中的保护作用

探讨在心肌缺血再灌注损伤中缺血预处理(IPreC)和后处理(IPostC)联合应用是否有协同保护作用。以雄性Wistar大鼠建立缺血再灌注模型。检测血清乳酸脱氢酶(LDH)和肌酸激酶(CK),通过氯化三苯基四氮唑方法估计梗死心肌面积,同时检测心肌组织中丙二醛(MDA),超氧化物歧化酶(SOD),谷胱甘肽过氧化物酶(GSH-Px)活性。结果IPreC、IPostC和两者联合使用后,在减少梗死面积,抑制LDH和CK以及MDA的增加,以及降低SOD和GSH-Px方面并没有协同保护作用。提示它们可能存在共同的信号通路机制。     

气体信号分子硫化氢在心肌缺血再灌注损伤中的心肌保护作用

体外循环技术目前已广泛应用于心脏外科手术,低温缺血导致的心肌缺血再灌注损伤(MIRI)是影响术后心功能恢复的重要因素。该文介绍硫化氢(H 2S)在MIRI中的作用和机制。     

洛伐他汀在大鼠心脏急性缺血再灌注中的延迟性心肌保护作用及其机制的研究

目的:探究洛伐他汀在大鼠心脏急性缺血再灌注中的延迟性心肌保护作用及其机制。方法:将24只Sprague-Dawley(SD)大鼠随机分为3组(n均=8):模型对照组(C);洛伐他汀(Lovastatin)组(L),胃管直接灌注洛伐他汀15mg·kg-1·d-12周;洛伐他汀复合L-硝基精氨酸甲酯(L-NAME)组(N),洛伐他汀15mg·kg-1·d-1直接灌胃2周同时腹腔注射L-NAME30mg·kg-1·d-1;2周后建立在体急性缺血再灌注心脏模型,监测缺血再灌注前后血流动力学各项指标,同时观察各组血脂水平及其血浆中丙二醛(MDA)、超氧化物歧化酶(SOD)、乳酸脱氢酶(LDH)以及肌酸激酶(CK)的变化情况。结果:L组和N组较C组心率明显减慢(P<0·01),缺血再灌注心律失常消失和再灌注时左心室内压下降最大速率(-dp/dtmax)下降程度减轻(P<0·05);洛伐他汀明显减少再灌注时血浆中MDA生成和LDH及CK的释放(P<0·01),并且提高心肌组织SOD活性(P<0·05),各项血脂指标不变。结论:洛伐他汀对大鼠心脏急性缺血再灌注时具有延迟性心肌保护作用。这种保护作用除与其增加一氧化氮(NO)合成相关外,还可能通过直接或间接方式稳定心肌细胞膜表面的离子通道,减少再灌注心律失常的发生,具体机制需待进一步实验证明。     

脂联素及其受体信号通路在肢体缺血预适应对心肌保护中的作用

目的 探讨心肌脂联素(ADP)及其受体(ADPR1)的磷脂酰肌醇-3激酶(PI3k)/磷酸化的蛋白激酶B(p-Akt)通路是否介导了肢体缺血预适应对心肌的保护作用. 方法 30只健康雄性SD大鼠,随机分为假手术组、心肌缺血-再灌注损伤组(MIRI组)、肢体缺血预适应(LIPC)组、PI3k特异性抑制剂(LY294002)预处理组和LIPC+ LY294002预处理组.分别采用RT-PCR法和Western blot法检测心肌组织中ADP和ADPR1的mRNA及PI3k和p-Akt蛋白的表达水平. 结果 与假手术组相比,MIRI组ADP (0.53±0.07比0.74±0.08)和ADPR1 (0.52±0.02比0.72±0.04)的mRNA值明显减少(P＜0.05);与MIRI组相比,LIPC组上调ADP(0.72±0.21)和ADPR1(0.80±0.02)的mRNA值(P＜0.05),LY294002则下调ADP (0.49±0.07)和ADPR1(0.52±0.02)的mRNA值(P＜0.05); LY294002+ LIPC组ADP和ADPR1的mRNA值,与MIRI组比较差异无统计学意义(P＞0.05).与假手术组相比,MIRI组PI3k(3.85±0.23)和p-Akt( 3.77±0.32)蛋白水平表达降低(P＜0.05),LIPC组PI3k(2.65±0.32)和p-Akt(2.26±0.27)蛋白水平较MIRI组表达增加(P＜0.05),LY294002组的PI3k和p-Akt蛋白几乎不表达(P＜0.05); LIPC+LY294002组大鼠心肌组织PI3k和p-Akt蛋白表达与LY90024预处理组相比差异无统计学意义(P＞0.05).心肌ADP水平与ADPR1 mRNA、PI3K和P-Akt蛋白水平呈正相关(r=0.886、0.756、0.745,P＜0.05). 结论 肢体缺血预适应通过激活ADP/PI3k/Akt信号通路发挥对心肌再灌注损伤的保护性作用.     

~(99)Tc~m-MIBI心肌显像在检测“罪犯”血管中的作用

目的　评价 99Tcm -甲氧基异丁基异腈 (MIBI)心肌灌注断层 (SPECT)显像在检测“罪犯”血管中的作用。方法　选择冠状动脉造影证实有多支血管病变并成功进行经皮腔内冠状动脉成形术 (PTCA)血流重建治疗的冠心病患者 5 2例。PTCA术前进行运动、静息、静脉滴注硝酸甘油介入 99Tcm - MIBI心肌显像 ,明确缺血与存活心肌数量最多的部位 ,以对应支配该部位的病变血管确定为“罪犯”血管。以术后疗效为标准 ,验证其准确性。结果　 5 2例中 ,冠状动脉造影发现病变血管 12 5支 ,心肌显像确定“罪犯”血管 5 2支。临床对确定的“罪犯”血管进行相应的血流重建治疗 ,随访均有良好疗效。结论　运动、静息、静脉滴注硝酸甘油介入 99Tcm- MIBI心肌显像检测“罪犯”血管准确可靠 ,实用可行     

促红细胞生成素在大鼠心肌缺血-再灌注损伤过程中的保护作用

目的探讨促红细胞生成素(EPO)在大鼠心肌缺血再灌注(MIRI)过程中的保护作用及其可能机制。方法建立大鼠心肌缺血再灌注模型。将雄性Wistar大鼠60只随机分为假手术组、缺血-再灌注组、EPO治疗组,每组20只。肢体Ⅱ导联心电图记录再灌注时的心律失常情况;比较再灌注末血清肌钙蛋白(cTnI)的变化;TTC染色法测定心肌梗死面积;电镜观察心肌超微结构的变化。结果EPO能明显减少再灌注时大鼠心律失常的发生,降低cTnI的水平,减小大鼠心肌梗死面积,与缺血再灌注组比较有统计学意义(P<0.05)。结论EPO对大鼠MIRI有明显的保护作用,其机制可能与减轻氧自由基及钙超载损害有关。     

Role of endogenous opioid peptides in the regulation of pituitary secretions

Identification of modulatory properties of morphine on certain hormonal secretions and that of opiate-receptor specific endogenous ligands has stimulated research in many fields, including role of opioid peptides in hypophysial secretion regulation. Availability of long-acting agonists and of antagonists of opioid peptides has provided data on their pharmacologic effects and possible role in hormonal physiology. The aim of the present report is to provide an update review of the influence of opioid peptides in hypophysial secretion regulation, while accepting that multiplicity of peptides and receptors does not allow formal conclusions to be drawn. At pharmacologic doses, opioid agonists stimulate prolactin and growth hormone secretion whereas that of LH and ACTH is inhibited. Secretion of TSH is little modified and that of ADH is stimulus-related. The opioid peptides are involved physiologically in the multifactorial regulation of gonadotropin secretion, other hypophysial secretions being mainly unaffected. Finally, "hypothalamic" amenorrhea appears to be the only pathologic model for which opioid peptides can be implicated. Finer analysis of physiologic role of endogenous opioid systems and their possible pathologic effects requires availability of selective agonists and notably antagonists.     

血浆内源性阿片肽与实验性肝硬变及腹水形成的作用

目的探讨血浆内源性阿片肽(Eop)在实验性肝硬变及腹水形成过程中的变化的意义.方法应用放射免疫法测定正常对照组及CCl4诱发大鼠肝硬变(n=37)及形成腹水(n=17)过程中血浆3种Eop的含量变化.结果肝硬变腹水组及肝硬变组血浆亮氨酸脑啡肽(L-ENK)含量均显著高于正常对照组(P均＜0.01),且都与血清清蛋白浓度呈显著负相关(r=-0.69,P＜0.01; r=-0.56,P＜0.01);与凝血酶原时间(PT)呈显著正相关(r=0.68,P＜0.01; r=0.69,P＜0.01). 同样两肝硬变组血浆强啡肽(DynA1-13)含量均显著高于正常对照组(P均＜0.01). 且与血清清蛋白浓度呈显著负相关(r=-0.64,P＜0.01; r=-0.59,P＜0.01),与PT呈显著正相关(r=0.65,P＜0.01; r=0.67,P＜0.01). 但两肝硬变组血浆L-ENK,DynA1-13与血ALT不相关. β-内啡肽(β-EP)的血浆含量在两肝硬变组及正常对照组中无显著差异.结论肝脏灭活功能受损是血浆小分子阿片肽(L-ENK与DynA1-13)含量升高的重要原因,后者又是实验性肝硬变腹水形成的主要原因之一. 而在β-EP体内灭活过程中,肝脏不起主要作用.     

间歇性低氧预处理对慢性缺血心脏保护作用的实验研究

目的:采用冠状动脉左前降支部分结扎的方法复制慢性心肌缺血的动物模型,观察间歇性低压低氧预处理对缺血心脏泵功能的保护作用。方法:成年雄性新西兰家兔22只,体质量2.02.5 kg,随机分为2大组:对照组（C组,n=11）和间歇性低压低氧预处理组（H组,n=11）。两组动物均先进行冠状动脉左前降支部分结扎,7 d手术恢复期后,H组动物开始间歇性低压低氧预处理（5000 m,6 h/d,连续7 d者为H1组,42 d者为H2组）,C组动物分为C1、C2组常规饲养（实验时间分别与H1、H2组相同）。按计划完成实验后,测定各组动物心率（HR）、左室收缩期内压最大变化速率（LVdp/dtm ax）及左室舒张期内压最大变化速率（-LVdp/dtm ax）,然后给予急性缺氧,重复测定上述指标,并与急性缺氧前所测相应各值比较,观察各组动物对急性缺氧的耐受性。同时观察各组动物的心肌细胞的超微结构及心肌VEGF mRNA的表达。结果:急性缺氧时,H2组HR的下降程度显著小于其它3组（P<0.01）;LVdp/dtm ax的下降程度显著小于C2组（8.5%vs30.5%,P<0.01）。恢复常氧后,H2组的LVdp/dtm ax恢复程度显著优于C2组（下降率为0.9%vs18.6%,P<0.01）;-LVdp/dtm ax恢复程度亦优于C2组及其它2组（P<0.05）。H2组动物心肌线粒体数量增加。经低氧预处理后心肌组织的血管内皮生长因子（VEGF）mRNA表达明显增高。结论:长期间歇性低压低氧预处理能增强缺血心脏对急性缺氧的耐受性,对慢性局灶性缺血心脏有保护作用。     

血浆内源性阿片肽升高与肝硬化外周动脉扩张及腹水形成的关系

目的：探讨血浆三种内源性阿片肽浓度变化，以了解它与肝硬化外周动脉扩张及腹水形成的关系。方法：用放免法检测了20例正常人，20例非肝病及50例肝硬化患者的血浆强啡肽（DynA1－13），亮啡肽（L－ENK）和β-内啡肽（β-EP）。结果：肝硬化无腹水组和有腹水组血浆DynA1－13和L-ENK浓度均明显高于正常对照组和非肝病对照组（P均＜0．01）；随病情加重，DynA1－13和L－ENK均呈上升趋势，肝硬化有腹水组的L－ENK亦明显高于无腹水组（P＜0．01）。相关分析表明：DynA1－13与A／G比值、L－ENK与A／G比值之间均呈显著负相关；血浆DynA1－13与L－ENK之间呈显著正相关。二组肝硬化患者血浆β－EP浓度与正常组和非肝病对照组比较，差异无显著性。结论：DynA1－13和L-ENK反映肝硬化的严重程度，并且在肝硬化外周动脉扩张及钠水潴因导致腹水形成中起重要作用β-EP不起主要作用。     

曲美他嗪对兔心肌梗死的短期心肌保护

目的观察曲美他嗪对急性心肌梗死（AMI）新西兰大白兔短期心肌保护作用。方法将心肌梗死后24h存活兔随机分为心肌梗死模型组（M组）和曲美他嗪组（Q组）,另设假手术组即只开胸不结扎组（s组）。曲美他嗪组（Q）经灌胃给曲美他嗪,其它两组给予等剂量的生理盐水10mg／Kg·d。2周后,检测各组血流动力学变化,取出心脏标本观察心肌梗死面积。结果在手术后两周与S组比较,M组左室舒张末压（LVEDP）、左室重量（LVW）、左窒重量指数（LVWI）,左室舒张末压在M组和Q组均减少,但M增加幅度小,左室重量和指数均较假手术组小,在曲美他嗪组中其左室重量和指数均较假手术组和模型组幅度大。结论曲美他嗪能够改善AMI后心功能及早期左室重构,在梗死早期具有营养和保护心肌的作用。     

维拉帕米对缺血再灌注损伤心肌保护机制的探讨

目的 :探讨维拉帕米对缺血再灌注损伤心肌的保护作用及其机制。方法 :①建立家兔心肌缺血再灌注模型。将 2 4只家兔按再灌注时限的不同及是否给予维拉帕米 (0 .2mg/kg静脉注射 )干预分为 4组 (A1、A2、B1、B2 ) ,测定各组的心肌梗死范围 ,并在电镜下对缺血再灌注心肌进行超微结构观察。②根据心肌缺血再灌注不同时限对 33只家兔进行分组 ,采用免疫组化法检测同一剂量维拉帕米 (0 .2mg/kg静脉注射 )对缺血再灌注不同时限心肌组织bcl 2蛋白的表达情况。结果 :①与 0 .85 %氯化钠组比较 ,维拉帕米组可明显减小心肌梗死范围(P <0 .0 1) ,改善其超微结构的变化。②与假手术对照组和 0 .85 %氯化钠组比较 ,维拉帕米组能显著上调缺血再灌注心肌bcl 2蛋白的表达 (P <0 .0 1)。结论 :维拉帕米可明显减轻心肌缺血再灌注损伤 ,其心肌保护机制可能是通过其促进缺血再灌注心肌组织bcl 2蛋白的表达来实现的     

Role of endogenous opioid peptides in the initiation of the midcycle luteinizing hormone surge in normal cycling women

While compelling evidence indicates a pivotal role for endogenous opioids in the regulation of GnRH-LH pulsatile activity during the late follicular and luteal phases of the menstrual cycle, the participation, if any, of the opioidergic mechanism in the initiation of the midcycle surge has not been examined. Accordingly, we measured serum LH, FSH, estradiol (E2) and progesterone (P4) levels daily during 2 consecutive cycles in 12 normal cycling women. After a control cycle, each woman was infused with naloxone (30 micrograms/kg.h) for 24 h starting 3 days before the anticipated spontaneous midcycle surge. Blood samples were obtained at 15-min intervals for 8 h before, during, and 16 h after the naloxone infusion. Serum LH and FSH concentrations were measured in all samples, and serum E2 and P4 concentrations at 2-h intervals. Pulsatile LH secretion was analyzed using the cluster program. The opioidergic blockade elicited a robust increase in LH pulsatile activity and a 3-fold rise in serum FSH levels in 6 of the 12 women. This increased gonadotropin secretion lasted more than 24 h and was characterized by a progressive increase in LH pulse amplitude, which was 9-fold greater during the last 8 h of naloxone infusion [mean LH pulse amplitude, 36.5 +/- 4.5 (+/- SE) vs. 4.1 +/- 0.4 IU/L; P less than 0.001]. This increase was accompanied by a corresponding increase in transverse mean serum LH levels (83.3 +/- 13 vs. 20.7 +/- 3.2 IU/L; P less than 0.001), but no alteration of the interpulse interval (93 +/- 11 vs. 85 +/- 4 min). The peak serum LH concentrations exceeded 100 IU/L in all 6 of these women. This naloxone-advanced gonadotropin surge, resembling closely the spontaneous midcycle surge, resulted in a significantly shortened (P less than 0.001) follicular phase and a more than 2-fold elevation of serum P4, followed by assumed ovulation and normal luteal function. These 6 women had serum E2 levels immediately before naloxone infusion that were comparable to those during the preovulatory peak during the control cycle. In the 6 women who did not have a naloxone-induced increase in gonadotropin secretion the preinfusion serum E2 levels were substantially lower (P less than 0.001) than the values during the control cycle. These findings suggest that a transient decrease in opioidergic activity may contribute to the initiation of the midcycle gonadotropin surge in women.     

缺血后处理对缺血再灌心肌保护作用的研究进展

20世纪80年代开始的溶栓治疗以及90年代以来兴起的经皮冠状动脉介入治疗(PCI)技术,是急性心肌梗死治疗史上里程碑式的进步。然而随之带来的再灌注心律失常、心肌舒缩功能障碍、代谢异常及心肌超微结构的改变,即心肌的缺血再灌注损伤,直接影响到患者的预后,因此,如何防止缺血/再灌注损伤已成为现今研究的重要内容。     

The role of endogenous peptides in the action of opioid analgesics

The observation that the narcotic antagonist naloxone could inhibit analgesia produced by electrical stimulation of the brain indicated the involvement of an endogenous chemical in the relief of pain. Multiple endogenous opioid peptides have been identified that have similar pharmacological properties to known narcotic analgesics. The biosynthesis, release, and degradation of opioid peptides have been studied in order to better understand how the manipulation of endogenous opioid systems can be used to produce or augment analgesia. The results of our studies reveal that various conditions and manipulations, such as electrical brain stimulation, acupuncture, stress, and the administration of opioid analgesics, can cause the release of endogenous opioid peptides and possibly endogenous nonpeptide substances. It has also been discovered that nonopioid peptides, such as cholecystokinin, calcitonin, and angiotensin II, can alter the action of opioid analgesics by antagonizing or potentiating their effects. An understanding of the role of endogenous peptides in endogenous opioid mechanisms is necessary for the development of new ways to treat pain and such other disorders as sleep apnea in children (sudden infant death syndrome), head injury, and opioid addiction that involve the activation or alteration of endogenous opioid systems.     

Stress and the endogenous opioid system. II. Stress, stress models and endogenous opioid peptides

Biochemical and pharmacological findings indicate an activation of the opioid system under certain stress influences. In this paper findings are discussed, according to which the activation of the opioid system depends on the temporary distribution pattern and the kind of the stressor. In response to stress opioid peptides are involved in excitatory and inhibitory processes. The participation of different types of opioids in central and peripheral stress-induced effects is discussed. Some findings suggest that beta-endorphin acts mainly centrally rather than peripherally, whereas the enkephalins take part in peripheral regulatory processes (gastrointestinal system, adrenal glands). Now there is evidence that the endogenous opioids modulate stress-induced effects, but there has been much controversy on how this fact should be established. These controversies mainly resulted from the many factors that influence activation.