缺血后适应对急性心肌梗死介入治疗的影响

目的研究缺血后适应对急性心肌梗死(AMI)患者急诊介入治疗后心肌梗死面积、心肌灌注和心功能的影响。方法选取12h内接受急诊经皮冠状动脉介入治疗(PCI)的急性心肌梗死患者122例,随机分入对照组(n=87)和(缺血)后适应组(n=35)。各例接受急诊PCI治疗。对照组梗死相关血管再通后不施加干预;缺血后适应组梗死相关血管再通后1min内应用低气压充盈和回撤球囊反复3次,每一过程各30s,术后测定血肌酸磷酸激酶(CK)、肌酸磷酸激酶同工酶(CK-MB)、Fas/FasL、ST回落率,校正TIMI帧数(CTFC)。术后6个月行单光子发射计算机断层显像(SPECT)检查。结果后适应组CK、CK-MB峰值明显低于对照组〔(1179±992)U/Lvs(1643±1021)U/L;(120±76)U/Lvs(160±88)U/L;P0.05)〕;后适应组FasL峰值明显低于对照组〔(3587.8±231.5)pg/mlvs(4412.4±105.7)pg/ml,P0.05)〕;sFas水平介入后24h开始较对照组显著下降(P0.05),且持续至7d(P0.05)。后适应组CTFC明显快于对照组(26.7±11.2vs31.4±9.5,P0.05),术后ST回落50%发生率明显高于对照组(74.3%vs54.0%)。术后6个月行SPECT检查,后适应组静息-再分布指数明显下降〔(10.8±9.6)%vs(18.5±12.8)%,P0.05〕。结论缺血后适应可以减低AMI患者心肌损伤、细胞凋亡、改善心肌灌注和缩小梗死面积。     

超速起搏预适应的延迟保护作用与环氧化酶2表达的关系

目的观察在超速心室起搏(VOP)预适应延迟保护阶段环氧化酶2(COX-2)的表达水平,从而探讨预适应延迟保护作用机制与COX-2的关系。方法健康的新西兰雄兔24只,随机分为3组,单纯结扎组、起搏组、起搏+放线菌素D组,每组8只,制作超速起搏预适应和缺血/再灌注动物模型,检测肌酸激酶(CK)、CK同工酶(CK-MB)的变化,动态描记再灌注时心电图变化,免疫组化染色检测COX-2抗原。结果缺血后起搏组CK、CK-MB的水平[(1492±474)IU/L和(614±182)IU/L]在再灌注时低于单纯结扎组[(2625±423)IU/L和(1332±178)IU/L]及起搏+放线菌素D组[(2071±390)IU/L和(1095±183)IU/L](P<0.01);单纯结扎组再灌注过程中共有5只(62.5%)发生心律失常,起搏+放线菌素D组也有4只(50%),而起搏组中无心律失常发生,起搏组和单纯结扎组中之间差异具有统计学意义(P<0.05),起搏组中COX-2的阳性表达程度明显高于其他两组。结论超速起搏预适应可以模拟缺血预适应,其延迟保护作用可能与COX-2的表达增加密切相关。     

缺血预适应对缺氧复氧后细胞离子稳态的影响及机制

研究缺血预适应对大鼠心肌细胞缺氧 复氧后离子稳态的影响及可能机制以及探讨缺血预适应抗心律失常的离子基础。采用Langdorff逆行灌流技术分离SD大鼠心肌细胞。按①缺血预适应组、②Glibenclamide干预缺血预适应组、③哇巴因 (OUB)干预缺氧 复氧组、④缺氧 复氧组、⑤Cromakalim(CRK)干预缺血预适应组、⑥OUB和CRK干预缺氧 复氧组、⑦正常对照组 ,分组孵育细胞 ,观察缺血预适应对缺氧 复氧后心肌细胞内钠、钾离子水平 ,细胞膜Na+ K+ ATP酶 (Na+ K+ ATPase)活性的影响。结果 :与单纯缺氧 复氧相比 ,缺血预适应使心肌细胞乳酸脱氢酶(LDH)漏出量下降 (2 1.75± 7.2 9vs 89.6 3± 2 4IU) ;同时维持Na+ K+ ATPase活性在较高水平 (6 .42± 0 .8vs 3 .18±0 .6 2 μmol·mg-1·h-1) ,保持细胞内较高的钾离子水平 (386 .5± 83vs 10 7.5± 2 9.96 μg/mg)和较低的钠离子水平(372 .5± 5 7.2 7vs 5 6 3 .0 7± 94.0 2 μg/mg)。此效应可被OUB及ATP敏感性钾通道阻滞剂Glibendamide所阻断。结论 :缺血预适应促进ATP敏感性钾通道的开放 ,减轻细胞膜损伤 ,维持细胞核Na+ K+ ATPase在较高水平 ,从而减少了缺氧 复氧后钠超载 ,增加了钾离子的再摄取 ,可能是缺血预适应稳定离子稳态的机制。细胞内外离子稳态的形成可?     

缺血后适应通过上调miRNA-21，miRNA-126发挥心脏保护效应

[摘要]：目的 探讨缺血后适应在大鼠心肌缺血再灌注时发挥保护作用的相关机制。方法将30只成年雄性SD大鼠每组10只,分为三组,假手术组：开胸后将6-0无损伤缝线穿过左冠状动脉前降支不阻断血管。缺血再灌注损伤组：使用6-0无损伤缝线阻断左冠状动脉30min后开放血管。缺血后适应组：缺血30min后,立即行缺血后适应(开放10s 阻断10s,反复3次）。采用伊文思蓝和氯化三苯基四氮唑染色法测定缺血面积和梗死面积;通过实时荧光定量PCR检测各组大鼠再灌注2 h体内miRNA-21,miRNA-126表达水平;通过ELISA法,硝酸还原酶法测定各组大鼠再灌注2 h体内TNF-α,Il-6、NO浓度。结果 Sham组未见明显心肌缺血和坏死面积,IPC组大鼠心肌AAR／LV与I/R组比较差异无统计学意义[(39.04±6.81)％比41.05± 8.04)％,P>0．05],IPO组大鼠心肌IS／AAR则低于IR组(25.64±5.76)％比(47.25±7.26)％, P<0.05]。I/R组、Ipost组术后miRNA-21,miRNA-126表达水平较Sham组升高,Ipost组升高更为明显。I/R组大鼠血清TNF-α,Il-6浓度明显高于Ipost组,I/R组血清NO浓度明显低于IPC组。miRNA-21与TNF-α,Il-6呈正相关（r=-0.934 、-0.925 ,p＜0.05,）,与NO无明显相关性（r=0.135,p＞0.05）。miRNA-126与TNF-α,IL-6呈负相关（r=-0.926、r=-0.935,p＜0.05）、与NO呈正相关性（r=0.553,p＜0.05）。结论 缺血后适应处理可减少大鼠心肌梗死面积,改善大鼠心肌缺血再灌注损伤。其心肌保护内在机制可能与调控miRNA-21,miRNA-126表达,抑制相关炎性因子释放有关。     

心肌缺血预适应对急性心肌梗塞近期预后的影响

目的:对首次急性心肌梗塞(AMI)发生前48h内是否发作过心绞痛的二组患者的临床经过和近期预后进行评价.方法:208例患者分为缺血预适应组(122例),无预适应组(86例),两组基础临床情况类似.结果:缺血预适应组比非缺血预适应组临床经过近期预后好,心肌梗塞范围小(P<0.001),血浆肌酸磷酸激酶峰值低(P<0.01),住院期间发生心衰、心源性休克、严重心律失常、心源性死亡率低(P<0.01).结论:急性心肌梗塞前48h内发作的心绞痛对心肌具有明确的保护作用,其机理可能和心肌缺血预适应有关.     

缺血、药物后适应及两者叠加对急性心肌梗死患者再灌注心肌的保护作用

目的 研究缺血后适应、药物后适应及两者叠加对择期冠脉介入(PCI)患者再灌注心肌的保护作用.方法 83例急性心肌梗死(AMI)择期行PCI的患者,随机分为四组,单纯PCI组16例,尼可地尔组21例,缺血后处理组27例及叠加组19例.尼可地尔组及叠加组在常规治疗基础上加用尼可地尔(喜格迈)5mg治疗,缺血后处理组及叠加组在再灌注开始Imin内缺血后处理,用药1 w后行PCI.所有患者测定血肌钙蛋白T(cTnT)、肌酸激酶同工酶(CK-MB)浓度、中性粒细胞数;术中测定校正TIMI帧数(CTFC);入院及治疗后行心脏彩超检查.结果 术后24h对照组cTnT、CK-MB水平明显高于尼可地尔组、缺血后处理组及叠加组;而尼可地尔组、缺血后处理组及叠加组之间未见统计学差异.对照组的CTFC(帧数)明显高于其他三组(31.19±2.86、26.43 ±1.57、27.19±1.47 vs.26.79±1.40,P＜0.05),而后三组之间未见统计学差异.四组患者术前中性粒细胞数未见统计学差异,术后24h对照组的中性粒细胞数明显高于其他三组[(6.94±0.74)× 109/L、(5.98±0.51)×109/L、(5.80±0.50)×109/L vs.(5.88±0.44)×109/L,P＜0.05].治疗6个月后对照组LVEF明显低于尼可地尔组、缺血后处理组及叠加组,WMSI明显高于其他三组;而尼可地尔组、缺血后处理组及叠加组之间未见统计学差异.结论 尼可地尔药物后适应与缺血后适应一样可以减轻心肌再灌注损伤,改善患者预后,而两者叠加未见加强作用.     

缺血预适应对心室颤动阈影响的研究

目的探讨兔右冠状动脉缺血预适应(ischemicpreconditioning,IP)对心室肌心室颤动阈的影响。方法根据顺序单脉冲刺激原理,采用RS2程序电刺激法,测量缺血再灌注组(IR组)(I30min+R30min)及缺血预适应(IP组)(I5min+R10min+I30min+R30min)在缺血30min(I30min)内及再灌注30min(R30min)内心室颤动阈(VFT)变化,并与正常对照组比较。结果①IR组及IP组于I30min内缺血心室肌VFT与正常对照组比较,VFT较低,差别有显著性(P＜0.01);与正常对照组比较,IR组于R30min内缺血心室肌VFT较低,差别有显著性(P＜0.01),但IP组同时期上述指标与正常对照组差异无显著性(P＞0.05);②IP组缺血心室肌于I30min、R30min内与IR组比较,VFT升高,差异有显著性(P＜0.01);③左心室IR组及IP组VFT与右心室相应指标比较,VFT较高,差异有显著性(P＜0.01)。结论右冠状动脉IP可提高缺血及再灌注心室肌的心室颤动阈。     

PTEN在心肌缺血预适应和后适应中的调控作用

目的探讨人第10号染色体缺失的磷酸酶及张力蛋白同源的基因(PTEN)/Akt信号通路在心肌缺血预适应和后适应中的作用。方法雄性SD大鼠60只,随机分为4组:假手术组(sham组)、缺血再灌注组(IR组)、缺血预适应组(Ipre组)及缺血后适应组(Ipost组)。建立动物模型,实验结束后,计算心肌梗死面积,测定血清肌酸激酶(CK)、乳酸脱氢酶(LDH)活性,检测缺血心肌PTEN m RNA和蛋白含量及p-Akt蛋白表达水平。结果与IR组比较,Ipre组和Ipost组的心肌梗死面积明显缩小,CK、LDH的活性降低,PTEN m RNA和蛋白的含量降低,p-Akt蛋白的水平升高(P0.05)。结论 PTEN/Akt信号通路在心肌缺血再灌注损伤中发挥重要作用,心肌缺血预适应和后适应通过调节PTEN/Akt信号通路的表达在缺血再灌注损伤中发挥保护心肌的作用。     

心肌缺血后适应及药物后适应的研究进展

急性心肌梗死(AMI)发生时,尽早恢复冠状动脉血流可减轻心肌的缺血、损伤和坏死,但同时也可能导致再灌注后的心肌损害.近年来,由于溶栓及血管成形术(PTCA)在AMI治疗中的广泛开展,再灌注损伤已成为不可回避的问题.在减轻再灌注损伤方面,缺血预适应(ischemic preconditioning, IPC)无疑是一项有效的措施,但因其操作问题和伦理原则导致临床应用受到一定限制[1].     

缺血预适应对急性心肌梗死Q—T离散度及室性心律失常的影响

目的探讨缺血预适应对急性心肌梗死Q-T间期离散度及室性心律失常的影响.方法根据318例首次急性心肌梗死患者发病前48h内是否发生心绞痛,分为缺血预适应组(186例)和无缺血预适应组(132例),另取健康人11l例作为对照组,测定每例校正Q-T间期离散度(Q-Tcd).结果无缺血预适应组Q-Tcd(70.47±12.05ms)明显大于缺血预适应组(55.96±10.4lms,P＜0.01),缺血预适应组明显大于对照组(42.47±9.17ms,P＜0.01).缺血预适应组室性心动过速、心室颤动及猝死的发生率明显低于无缺血预适应组(P均＜0.01).结论缺血预适应可明显减小急性心肌梗死时的Q-T离散度,降低室性心律失常和猝死的发生率.     

Three layer functional model and energy exchange concept of aging process

Relying on a certain degree of abstraction, we can propose that no particular distinction exists between animate or living matter and inanimate matter. While focusing attention on some specifics, the dividing line between the two can be drawn. The most apparent distinction is in the level of structural and functional organization with the dissimilar streams of ‘energy flow’ between the observed entity and the surrounding environment. In essence, living matter is created from inanimate matter which is organized to contain internal intense energy processes and maintain lower intensity energy exchange processes with the environment. Taking internal and external energy processes into account, we contend in this paper that living matter can be referred to as matter of dissipative structure, with this structure assumed to be a common quality of all living creatures and living matter in general. Interruption of internal energy conversion processes and terminating the controlled energy exchange with the environment leads to degeneration of dissipative structure and reduction of the same to inanimate matter, (gas, liquid and/or solid inanimate substances), and ultimately what can be called ‘death.’ This concept of what we call dissipative nature can be extended from living organisms to social groups of animals, to mankind. An analogy based on the organization of matter provides a basis for a functional model of living entities. The models relies on the parallels among the three central structures of any cell (nucleus, cytoplasm and outer membrane) and the human body (central organs, body fluids along with the connective tissues, and external skin integument). This three-part structural organization may be observed almost universally in nature. It can be observed from the atomic structure to the planetary and intergalactic organizations. This similarity is corroborated by the membrane theory applied to living organisms. According to the energy nature of living matter and the proposed functional model, the decreased integrity of a human body's external envelope membrane is a first cause of the structural degradation and aging of the entire organism. The aging process than progresses externally to internally, as in single cell organisms, suggesting that much of the efforts towards the restoration and maintenance of the mechanisms responsible for structural development should be focused accordingly, on the membrane, i.e., the skin. Numerous reports indicate that all parts of the human body, like: bones, blood with blood vessels, muscles, skin, and so on, have some ability for restoration. Therefore, actual revival of not only aging tissue of the human body's membrane, but the entire human body enclosed within, with all internal organs, might be expected. We assess several aging theories within the context of our model and provide suggestions on how to activate the body's own anti-aging mechanisms and increase longevity. This paper presents some analogies and some distinctions that exist between the living dissipative structure matter and inanimate matter, discusses the aging process and proposes certain aging reversal solutions.     

Unusual responses of nocturnal pineal melatonin synthesis and secretion to swimming: Attempts to define mechanisms

Abstract: The effect of swimming at night on rat pineal melatonin synthesis was compared with that of light exposure at night. Rats were forced to swim at 0030 hr (lights out at 2000 hr) and sacrificed by decapitation 15 and 30 min later, immediately after swimming. Other groups of animals were exposed to white light (650μW/cm²) for 15 and 30 min at same time. Swimming caused a rapid and highly significant drop in the melatonin content in the pineal gland; however, the activity of N-acetyltransferase (NAT), the supposed rate limiting enzyme in the melatonin production, was not changed. Despite the drop in pineal melatonin levels, serum concentrations of the indole remained elevated in the rats that swam. In contrast, melatonin levels in the pineal and serum of light exposed rats fell precipitously, accompanied by a significant suppression of NAT activity. Since we anticipated that the strenuous exercise associated with swimming may induce release of artrial natriuretic peptide (ANP) from the heart, which in turn could cause the release of pineal melatonin, in a second study we injected physiological saline intravenously to stretch the cardiac muscle and release ANP. Three milliliters of normal saline was injected during the day into the jugular vein of anesthetized rats that were pretreated with isoproterenol to stimulate pineal melatonin production. Animals were killed 15 min after the saline injection, and pineal NAT activity and pineal melatonin levels were measured. The saline injections caused no alteration in the elevated levels of either NAT or melatonin. These data suggest that the disparity in pineal NAT activity (which was high) and pineal melatonin (which was low), in animals swum at night, may not be caused by ANP which is released during strenuous exercise such as swimming.     

The immunoneuroendocrine role of melatonin

Abstract: A tight, physiological link between the pineal gland and the immune system is emerging from a series of experimental studies. This link might reflect the evolutionary connection between self-recognition and reproduction. Pinealectomy or other experimental methods which inhibit melatonin synthesis and secretion induce a state of immunodepression which is counteracted by melatonin. In general, melatonin seems to have an immunoenhancing effect that is particularly apparent in immunodepressive states. The negative effect of acute stress or immunosuppressive pharmacological treatments on various immune parameters are counteracted by melatonin. It seems important to note that one of the main targets of melatonin is the thymus, i.e., the central organ of the immune system. The clinical use of melatonin as an immunotherapeutic agent seems promising in primary and secondary immunodeficiencies as well as in cancer immunotherapy. The immunoenhancing action of melatonin seems to be mediated by T-helper cell-derived opioid peptides as well as by lymphokines and, perhaps, by pituitary hormones. Melatonin-induced-immuno-opioids (MHO) and lymphokines imply the presence of specific binding sites or melatonin receptors on cells of the immune system. On the other hand, lymphokines such as -γ-interferon and interleukin-2 as well as thymic hormones can modulate the synthesis of melatonin in the pineal gland. The pineal gland might thus be viewed as the crux of a sophisticated immunoneuroendocrine network which functions as an unconscious, diffuse sensory organ.     

Melatonin and photoperiodic time measurement: Seasonal breeding in the sheep

Abstract: Well-established circadian physiology supports the view that photoperiodic time measurement utilizes the coincidence between the presence of light and a photosensitive phase of a 'biological clock' to alter reproductive status—the so-called external coincidence model of seasonal breeding. In this review, we examine the mechanism whereby photoperiod interacts with presumed suprachiasmatic nuclei activity to allow endogenous melatonin to normally synchronize reproductive activity to the optimal time of year. The Romney Marsh sheep is particularly explored as an experimental model. It is suggested that the on/off activity of seasonal reproduction may be a robust mechanism able to be predictably manipulated by the judicious use of the light/dark cycle and exogenous melatonin, but firmly based on circadian principles.     

Response of rat pineal melatonin to calcium, magnesium, and lithium is circadian stage dependent

Abstract: Herein we documented the response of pineal melatonin production to electrolytes known to be effective on pineal function in view of a possible circadian stage dependence. We studied the release of melatonin by perifused rat pineal glands at 2 different circadian stages corresponding to the middle of the light and dark periods, i.e., respectively, 7 and 19 HALO (Hours After Light Onset, L:D = 12:12). The initial efflux rates were, as expected, much higher in the perifusates of glands removed from rats sacrificed during the dark phase than of those removed during the light phase. After 3 hr of perifusion, melatonin release reached similar levels which were found constant up to the 8th hr of perifusion, whatever the circadian stage. Perifusion of the glands with physiological concentrations for the rat of calcium (5.2 mmol/1) and magnesium (1.34 mmol/1) resulted in a stimulatory effect on the pineal glands removed from rats sacrificed in the middle of the dark period (19 HALO), whereas no effects were observed on the pineal glands removed from rats sacrificed during the light (7 HALO). Lithium (0.28 and 0.55 mmol/1) was ineffective on melatonin release in pineal glands removed 7 and 19 HALO. Our results show differences in the initial efflux rates of melatonin and in the response of perifused pineal glands to calcium and magnesium according to the circadian stage.     

Changes in connexin43, the gap junction protein of astrocytes, during development of the rat pineal gland

Abstract: The abundance of gap junctions between rat pineal astrocytes formed by connexin43 (Cx43) was studied during development. Levels and distribution of Cx43 were measured by immunoblotting and indirect immunofluorescence, respectively. The amount of Cx43 in cells located within the gland was low until about the 7th postnatal day and increased to adult values between the 14th and 21st days postpartum. Although astrocytes, recognized by their vimentin immunoreactivity, were scarce before birth, they were abundant by the 7th postnatal day suggesting that the low levels of Cx43 found at this age corresponded to a low expression of this protein. Localization of the immunoreactivity to Cx43 and vimentin showed a close correlation, indicating that mature or immature pineal astrocytes form gap junctions made of Cx43. Since Cx43 levels attained their adult values at about the time the innervation and the functional state of the gland reached maturity (2–3 weeks after birth), it is proposed that astrocyte gap junctions are involved in the function of the adult rat pineal gland.     

Conservative management of perforated duodenal diverticulum： A case report and review of the literature

Duodenal diverticula are a relatively common condition. They are asymptomatic, unless they become complicated, with perforation being the rarest but most severe complication. Surgical treatment is the most frequently performed approach. We report the case of a patient with a perforated duodenal diverticulum, which was diagnosed early and treated conservatively with antibiotics and percutaneous drainage of secondary retroperitoneal abscesses. We suggest this method could be an acceptable option for the management of similar cases, provided that the patient is in good general condition and without septic signs.