局部血管内低剂量促红细胞生成素和联合 tPA 注射对大鼠脑缺血的影响

目的：探讨局部血管内低剂量促红细胞生成素（ erythropoietin,EPO）联合组织纤溶酶原激活剂（ tissue plasminogen activator,tPA）注射是否可以降低 tPA 单独应用时的不良反应及机制。方法成年雄性 Sprague-Dawley 大鼠进行大脑中动脉闭塞手术,将健康雄性 SD 大鼠按数字表法随机分为5组,每组10只,分别缺血2 h 和4 h,再灌注30 min 后通过大脑中动脉单独注射 tPA,或联合注射 EPO（800 IU/ kg）及 tPA。结果局部血管内低剂量 EPO 联合 tPA 注射可以减小大鼠脑缺血再灌注24 h 后的病死率、改善神经功能、减少脑水肿和脑出血,并且没有产生血液学不良反应。局部血管内低剂量 EPO 联合 tPA 注射组与0.9%（质量分数）氯化钠注射液联合 tPA 注射组比较,p-AKT 和 p-ERK 的表达水平明显升高。结论大鼠脑缺血后,局部血管内低剂量 EPO 和 tPA 联合使用,可减少 tPA 单独使用时的不良反应,并发挥 EPO 的神经保护作用,可能与 AKT 和 ERK 通路激活有关。     

NRK-52E缺血再灌注损伤时Kim-1、NO变化及虫草对其的干预作用

目的通过抗霉素A(Antimycin A,AA)刺激大鼠肾小管上皮细胞(NRK-52E)模拟体外缺血再灌注损伤过程,观察缺血再灌注损伤时NRK-52E中肾损伤分子-1(kidney injury molecule-1,Kim-1)及NO表达的变化及冬虫夏草对其的干预作用。方法将体外培养的NRK-52E分为对照组、模型组和虫草组。虫草组予含40 mg/L虫草原液的培基预处理。培养72 h后NRK-52E去除培基,予10-10 mol/L抗霉素A(AA)刺激1 h,模拟体外缺血过程,1 h后再加入培基,模拟体外再灌注损伤过程。分别在AA刺激前,AA刺激后1 h,加入培基再灌注10 min,30 min,60 min,120 min共6个时间点终止实验。用流式细胞仪以Annexin V/PI双染法检测细胞凋亡;分别用硝酸还原酶法和ELISA检测细胞上清液Kim-1与NO浓度;用RT-PCR法观察Kim-1 mRNA表达。结果 NRK-52E细胞经AA刺激后,细胞凋亡率显著增高,同时Kim-1表达上调;缺血60 min较缺血前Kim-1蛋白水平增加了3.1倍,再灌注10 min增加了3.6倍(P<0.05)。Kim-...     

丹参酮ⅡA保护大鼠肾移植术后缺血再灌注损伤的机制研究

目的 观察丹参酮ⅡA对大鼠同种异体肾移植术后肾脏保护性因子Klotho基因和氧化应激对肾功能等的影响,分析其对肾缺血/再灌注损伤的保护作用机制.方法 SD大鼠48只,分为假手术组、缺血/再灌注组、丹参酮A组和B组,采用同种异体左肾移植手术.术后丹参酮A、B组分别用5％和10％丹参酮按5mL/kg灌胃治疗7d,假手术组和缺血/再灌注组按5mL/kg体积分别灌服生理盐水.采用RT-PCR法检测肾组织Klotho基因表达,从尾静脉采血测定4组大鼠肾功能:肌酐(Cr)、尿素氮(BUN)、胱抑素C(Cys C)]指标.检测肾组织匀浆中氧化物歧化酶(SOD)、乳酸脱氢酶和血清丙二醛(MDA).结果 丹参酮A组和B组大鼠肾移植术后BUN、Cr、CysC显著降低,肾组织匀浆中MDA降低、SOD提高,Klotho蛋白和lotho-mRNA明显上调,与缺血/再灌注组比较,P ＜0.05.丹参酮A组和B组组间比较,P＞0.05.结论 丹参酮Ⅱ A在肾移植术后可提高SOD活性、抑制MDA的产生,上调Klotho蛋白和lotho-mRNA表达,抑制肾小管上皮细胞凋亡而达到肾缺血/再灌注损伤的保护作用.     

缺血性脑卒中并发低钙血症机制及临床意义

目的 :探讨缺血性脑卒中并发低钙血症的机制及临床意义。方法 :回顾性分析 10 2 8例缺血性脑卒中临床及血清钙资料。结果 :10 2 8例中并发低钙血症者 14例 ,发生率为 1.36 % ,以病灶部位为基底节区者发生率最高 (6 .87% ,P <0 .0 5 ) ;发生低钙血症者神经精神症状以潜在型手足抽搦为主 (5 7.14 % ,P <0 .0 1) ;并发低钙血症者较血清钙正常者病死率为高 (P <0 .0 5 )。结论 :下丘脑 -垂体 -肾上腺皮质轴功能紊乱是引起缺血性脑卒中并发低钙血症的主要原因之一。     

Noninvasive finding of local repolarization changes in the heart using dipole models and simplified torso geometry

Two inverse methods using dipole models for noninvasive assessment of local repolarization changes were investigated and compared in the simulation study. Lesions with changed repolarization were modeled by shortening of the action potential durations in ventricular regions typically influenced by occlusion of coronary arteries. Corresponding body surface potentials were computed using a multiple dipole model of the cardiac generator and an inhomogeneous torso model. Position of each lesion was then estimated by an inverse solution to a single dipole and to a group of five neighbouring dipoles. For both methods the lesion localization error was evaluated and its dependence on the lesion size and the noise in input data was studied. When no noise was present in the input data, the use of the inverse method to a group of dipoles instead of a single dipole resulted in an unsubstantial reduction of the mean localization error of small lesions from 0.6 to 0.5 cm. For medium and especially for large lesions the mean localization errors decreased significantly from 1.1 to 0.6 cm and from 2.3 to 1.0 cm, respectively. The inverse solution to a group of five dipoles was more sensitive to noise. However, for large lesions it still gave better results than the solution to a single dipole if the signal to noise ratio was higher than 30 dB.     

Volatile anaesthetics and cardioprotection – lessons from animal studies

Volatile anaesthetics emerged as important cardioprotective agents in both animal models of ischaemia/reperfusion injury and humans with coronary artery disease. Their administration before a prolonged ischaemic episode is known as anaesthetic preconditioning, whereas when given at the very onset of reperfusion, the strategy is termed anaesthetic postconditioning. Both types of anaesthetic conditioning reduce, albeit not to the same degree, the extent of myocardial injury. They share similar, albeit not identical, intracellular signal transduction pathways with their widely investigated counterparts, ischaemic pre‐ and postconditioning. Despite a wealth of preclinical evidence for cardioprotection for anaesthetic conditioning strategies, their translation into clinical therapy has been rather disappointing. This review highlights the major findings on the cardioprotective effects of volatile anaesthetics in experimental settings. It explores hypotheses that may explain the lack of efficacy observed in several past clinical studies paving the way for future preclinical and translational studies.     

Myocardial protection in reperfusion with postconditioning

Reperfusion is the definitive treatment for coronary occlusive disease. However, reperfusion carries the potential to exacerbate lethal injury, termed ‘reperfusion injury’. Studies have suggested that reperfusion injury events are triggered during the early moments of reflow, and determine, in part, the severity of downstream manifestations of postischemic injury, including endothelial dysfunction, infarction and apoptosis. The application of brief iterative episodes of reflow (reoxygenation) and reocclusion (ischemia, hypoxia) at the immediate onset of reperfusion, which has been termed ‘postconditioning’ by the authors, reduces many manifestations of postischemic injury, notably infarct size, apoptosis, coronary vascular endothelial injury and reperfusion arrhythmias. Cardioprotection with postconditioning has been reported to be comparable with that observed using the gold standard maneuver ischemic preconditioning. In contrast to preconditioning, which exerts its effects primarily during the index ischemia, postconditioning appears to exert its effects during reperfusion alone. Postconditioning modifies the early phase of reperfusion in ways that are just beginning to be understood. It appears to first: reduce the oxidant burden and consequent oxidant-induced injury; secondly, attenuate the local inflammatory response to reperfusion; and thirdly, engage end effectors and signaling pathways implicated in other cardioprotective maneuvers, such as ischemic and pharmacologic preconditioning. Postconditioning seems to trigger the upregulation of survival kinases principally known to attenuate the pathogenesis of apoptosis and possibly necrosis. The postconditioning phenomenon has been reproduced by a number of independent laboratories and has been observed in both large and small animal in vivo models, as well as in ex vivo and cell culture models. In contrast to preconditioning, postconditioning may have widespread clinical application because it can be applied during reperfusion at the point of service for angioplasty, stenting, cardiac surgery and organ transplantation.     

不同预处理中线粒体KATP通道开放对未成熟心肌的作用

目的　了解线粒体ATP敏感性钾通道 (mKATP)开放在不同预处理过程中对幼兔心脏的影响 ,并探讨其机制。方法　幼兔 (小于 2 8d) 34只随机分成 5组 ,对照组 (n =8) :平衡 30min后缺血再灌注 ;二氮嗪预处理组 (n =8) :缺血前二氮嗪 ( 10 0 μmol/L)灌注 5min后重碳酸盐缓冲液 (KH液 )冲洗 10min ,St.ThomasⅡ (STH)停跳 ;二氮嗪 + 5 羟葵酸 ( 5 HD)预处理组 (n =5 ) :二氮嗪 ( 10 0 μmol/L)和 5 HD( 10 0 μmol/L)一起灌注 5min ;缺血预处理 (IPC)组 ( n =8) :平衡 15min后全心缺血 5min ,复灌 10min行IPC ,STH停跳 ;IPC + 5 HD组 (n =5 ) :IPC前用 5 HD ( 10 0μmol/L)灌注 5min。采用LangendOrff模型 ,常温 ( 38℃ )缺血 30min ,复灌 45min。 结果　缺血 /再灌注 (I/R)后二氮嗪组的线粒体评分较IPC组 (P <0 .0 5 )和对照组 (P <0 .0 1)低 ,IPC前给予 5 HD后线粒体评分仍较对照组低 (P <0 .0 5 )。二氮嗪组和IPC组左室发展压力 (LVDP)、左室压力上升和下降最大速率 (±dp/dtmax)恢复在多个时间点上均优于对照组 ,心肌组织ATP含量高于对照组 (P <0 .0 1) ,心肌酶较对照组降低 (P <0 .0 1)。结论　二氮嗪预处理能产生与IPC相似的心肌保护作用 ,并且对线粒体的保护效果较IPC好。mKATP通道和细胞膜KATP     

缺血预处理对肺缺血再灌注损伤中细胞因子生成的影响

目的　探讨缺血预处理 (IPC)对肺缺血再灌注 (I/R)损伤的保护作用及其对细胞因子生成的影响。　方法　 36只大白兔分为 3组 :对照组、I/R组和IPC组。通过阻断左肺门造成兔在体I/R损伤 ,观察IPC对肺I/R损伤的保护作用 ,指标为肺组织湿干重比、肺通透性指数及支气管肺泡灌洗液(BALF)中白细胞分类计数 ;以双抗体夹心酶联免疫吸附试验法检测血清中肿瘤坏死因子α(TNFα)、白细胞介素 6(IL 6)、白细胞介素 8(IL 8)的含量。　结果　肺I/R损伤后 ,I/R组肺组织湿干重比、肺通透性指数及BALF中性粒细胞百分比分别为 9 73± 1 1 4、(41 62± 5 77)× 1 0 - 4和 (58 1± 1 0 0 ) % ;IPC组分别为 6 2 3± 0 69、(2 0 31± 4 0 3)× 1 0 - 4和 (2 3 8± 5 2 ) % ,两组差异有极显著意义 (P <0 0 1 )。I/R组血清TNFα、IL 6和IL 8含量分别为 (0 90 78± 0 1 0 6 2 )、(0 2 1 3 7± 0 0 598)和 (0 72 1 1± 0 0 979)ng/ml,IPC组分别为 (0 7478± 0 0 843)、(0 1 2 71± 0 0 0 89)和 (0 590 3± 0 0 746)ng/ml,较I/R组显著降低 (P <0 0 1 )。　结论　IPC对I/R损伤有显著的保护作用 ,机理可能与其抑制炎性细胞因子TNFα、IL 6和IL 8的合成和释放 ,从而减轻中性粒细胞的浸润与激活有关。