无创性缺血预处理延迟相心肌保护作用及其机制的研究

目的　通过建立大鼠在体缺血再灌注模型 ,探索无创性缺血预处理 (NIPC)延迟心肌保护作用 ,以及核因子κB (NF κB)在此过程中所起的作用。方法　将SD雄性大鼠随机分成 4组 ,Ⅰ组 (I/R组 ) ;Ⅱ组 (NIPC组 ) ;Ⅲ组 (PDTC NIPC组 ) ;Ⅳ组 (PDTC组 )。PDTC为NF κB特异性抑制剂。建立体内大鼠缺血再灌注模型 ,分别结扎前降支 4 5min ,复灌 30min ,观察大鼠心肌超微结构、心律失常发生率 ,并测量超氧化物歧化酶 (SOD)、丙二醛(MDA)、热休克蛋白 70 (HSP70 )、NF κB的值 ;复灌 2h测定心肌梗死面积。其中NIPC为I/R前 2 4h采用止血带阻断双下肢血流 5min ,复灌 5min ,反复 3个循环。结果　Ⅱ组心功能恢复优于其它 3组、心梗面积小于其它 3组(P <0 0 5 ,P <0 0 1) ;心律失常发生率较其他 3组低 (均P <0 0 5 )。Ⅲ组的各项结果与另外 3组比较均有统计学意义 ,Ⅰ和Ⅳ组的结果差别没有统计学意义。结论　无创性缺血预处理可以起到延迟相心肌保护作用 ;NF κB在预处理过程中可以诱导产生心肌保护蛋白 ,但在心肌持续缺血过程中作为一种重要炎症因子可加重心肌损伤。     

脂氧素A4对心肌缺血再灌注损伤的保护作用

Objective To investigate the roles of lipoxin A4, an endegenous lipid mediator with wide anti-inflammatory fea- tures, in attenuating myocardial ischemia-reperfusion injury and the possible mechanisms. Methods Thirty male KM mice were divid- ed randomly into three groups, 10 in each: ischemia-reperfusion group (group A), lipoxin A4 (0.1 mg/kg) group (group B) and Zn- PP (Zinc protoporphyrin Ⅸ, 25 mg/kg)phus lipoxin A4 (0.1 mg/kg)group (group C). A ischemia-reperfusion heart model was de- veloped by ligating the lift anterior descending branch of the coronary artery. A dine of 10% dehydrated alcohol in 0.2 ml for group A, a dose of isochoric lipoxin A4 for group B and a dose of isochoric ZnPP + lipoxin A4 for group C was infused into the ascending aorta through a catheter, which was kpassing the right common carotid artery, 30 minutes after reperfusion. The concentration of serum TNF-α, activities of serum crestine kinase(CK) and lactate dehydrogenase (LDH), activities of myeloperoxidase (MPO) and malond- ialdehyde (MDA) and the cell apoptosis rate in the myocardial tissue were measured 5 hours after reperfusion. Pathological features of the inflammatory infiltration in the myocardium were also observated.Results As compared with group A, the inflammatoryry infiltra- tion in the ischemic and necrotic regions tithe myocardium was reduced, with group C in the intermediate range. The serum activities of CK and LDH wine significantly lower in group B and C than that in group A, and the lowest activities were detected in group B. Similar findings were observed for MPO, an indicator for neutrophil infiltration, and MDA, an indictor for cell injury caused by oxy- gen radicals, in the myocardium. The concentration of TNF-α and the rate of cadiocyte apoptosis were decreased significantly in group B(P < 0.01). ZnPP, an inhibitor of heine oxygenase (HO)-1, attenusted the above protective effects of lipoxin A4 significantly (P<0.05). Conclusion Lipoxin A4 has protective effects against myocardial ischemia-reperfusion injury, and HO-1 may have a potential role in the protectve mechanisms of lipoxin A4, probably pertly by means of reducing the production of reactive oxygen spe- cies and TNF-α, decreasing the activation and infiltration of neutrophils, alleviating inflammatory damage and avoiding apoptosis.     

热休克蛋白70对兔未成熟心肌和心肌间质的影响

目的: 探讨热休克蛋白70(HSP70)对未成熟心肌和心肌间质的影响. 方法:健康新生长耳大白兔12只随机分为2组. 对照组(C组):ip生理盐水0.4 mL,24 h后取离体心脏,常规建立Langendorff离体心脏灌注模型,灌注15 min转为工作心15 min后停灌45 min,恢复灌注15 min改为工作心30 min;实验组(E组):ip去甲肾上腺素, 24 h后取离体心脏,方法同对照组. 测定心肌细胞中HSP70含量、血流动力学指标、心肌含水量(MWC)、心肌肌酸激酶(CK)和乳酸脱氢酶(LDH)漏出率、三磷酸腺苷(ATP)含量、超氧化物歧化酶(SOD)和丙二醛(MDA)含量、心肌组织羟脯氨酸(HP)含量、内皮素(ET) 含量、心肌细胞内Ca2 含量、心肌线粒体Ca2 -ATPase活性及其Ca2 含量、心肌线粒体合成ATP能力[ATP]m,心肌超微结构. 结果:E组HSP70含量明显高于C组(P<0.01);MWC低于C组(P<0.05);ATP含量、SOD活性、心肌线粒体Ca2 -ATPase活性、[ATP]m, HP含量优于C组(P<0.01),MDA含量、CK, LDH漏出率、心肌细胞内Ca2 含量、心肌线粒体Ca2 含量、ET含量低于C组(P<0.01),心肌超微结构损伤较C组明显减轻. 结论:HSP70对缺血再灌注未成熟心肌和心肌间质具有明显的保护作用.     

热休克蛋白70对离体心脏心肌间质的保护作用

目的探讨热休克蛋白70（HSP70）对大鼠离体心脏心肌间质的影响。方法Wistar大鼠16只，分为2组：对照组（C，n=8），腹腔注射生理盐水0．4ml，24h后取离体心脏灌注HTK心脏保护液，4℃保存3h后建立Langendorff灌注模型，灌注KH液2h；实验组（E，n=8），腹腔注射重酒石酸去甲肾上腺素，24h后取离体心脏，方法同对照组。以心肌细胞中HSP70含量、血流动力学指标、心肌组织羟脯氨酸（HP）、内皮索（ET）含量和心肌超微结构等作为观察指标。结果HSP70含量E组与C组比较明显增高；E组心功能恢复方面优于C组（P〈0．05），HP含量优于C组（P〈0．01），ET含量低于C组（P〈0．01），心肌超微结构损伤较C组明显减轻。结论HSP 70对供心心肌间质具有保护作用。     

不同缺血预处理对未成熟心肌细胞功能的影响

目的比较不同方法的缺血预处理对未成熟心肌细胞功能的影响。方法采用Langendorff离体心脏灌注模型。分为4组:缺血/再灌注(I/R)组,离体心脏灌注15min转为工作心15min后停灌45min,恢复灌注15min改为工作心30min;心脏缺血预处理(MIP)组:离体心脏灌注15min转为工作心15min后反复2次缺血5min/再灌注5min,然后重复I/R组缺血/再灌注方法;肾缺血预处理(RIP)组:反复三次阻断左肾动脉5min,放开5min,切取心脏,重复I/R组方法;双下肢缺血预处理(DLIP)组:反复3次捆扎双下肢5min,松开5min,切取心脏,重复I/R组方法。以血清肌酸激酶(CK)和乳酸脱氢酶(LDH)漏出率、心肌组织三磷腺苷(ATP)和丙二醛(MDA)含量、超氧化物歧化酶(SOD)活性、心肌细胞内Ca2+含量、心肌线粒体Ca2+-ATPase活性及其Ca2+含量、心肌线粒体合成三磷腺苷能力[ATP]m作为观察指标。结果MIP、RIP及DLIP组ATP含量、SOD活性、心肌线粒体Ca2+-ATPase活性、[ATP]m均高于I/R组(P<0.01),MDA含量、CK、LDH漏出率、心肌细胞内Ca2+含量、心肌线粒体Ca2+含量均低于I/R组(P<0.01)。结论肾缺血预处理、双下肢缺血预处理与心脏缺血预处理有同等的心肌细胞保护作用。     

协和医院10年科研工作情况调查分析

医学科研成果的多少、质量的高低可从一个侧面反映教学医院的整体科研水平,同时也是衡量该单位教学质量、医疗水平的重要标志之一[1]。华中科技大学同济医学院附属协和医院是一所历史悠久、传统优良,集医疗、教学、科研为一体的大型综合医院。该院拥有一大批优秀的医学专门人才及著名专家,他们长期以来积极开展医学科学研究,取得了大批科研成果,使得协和医院的科研能力得到很大提高。为了真实地了解协和医院科学研究工作的现状,科学地评价协和医院科研课题的质量,找出协和医院科研工作的优势及存在的问题,拟进行了本调查研究。1研究对象与方…     

白细胞介素2、10和转化生长因子β1在大鼠心脏移植急性排斥反应中的表达

目的研究白细胞介素2、10(IL-2、IL-10)与转化生长因子β1(TGF-β1)在大鼠心脏移植急性排斥反应中的表达.方法分两组建立同种大鼠颈部心脏移植模型对照组(n=25)和新赛斯平组(CsA组,n=25),各5例观察移植心脏存活时间,于移植术后第1、5、7、14天分别取移植心组织各5例,半定量RT-PCR的方法动态检测移植心脏中IL-2、IL-10及TGF-β1的表达情况.结果对照组移植心存活时间为(8.6±1.5)d,CsA组移植心存活时间为(20.4±5.1)d,两组间移植心存活时间差异有显著性意义(P<0.01).两组中TGF-β1表达强度不同,对照组中表达较CsA组中弱,二者间差异有显著性意义(P<0.01).IL-2在对照组中先增高,于术后第5～7天达高峰,之后逐渐降至术后第14天的较低水平,而CsA组中IL-2则维持在较低水平.IL-10在对照组中表达维持于较低水平,CsA组中IL-10表达增高,于第7天达峰值,并维持高水平;两组间IL-10的表达差异有显著性意义(P<0.01).结论 IL-10和TGF-β1的产生和表达因CsA的干预而增加,IL-2的表达则受到抑制,CsA的干预明显延长了移植心脏的存活时间.     

脂氧素A4对心肌缺血再灌注损伤的保护作用

Objective To investigate the roles of lipoxin A4, an endegenous lipid mediator with wide anti-inflammatory fea- tures, in attenuating myocardial ischemia-reperfusion injury and the possible mechanisms. Methods Thirty male KM mice were divid- ed randomly into three groups, 10 in each: ischemia-reperfusion group (group A), lipoxin A4 (0.1 mg/kg) group (group B) and Zn- PP (Zinc protoporphyrin Ⅸ, 25 mg/kg)phus lipoxin A4 (0.1 mg/kg)group (group C). A ischemia-reperfusion heart model was de- veloped by ligating the lift anterior descending branch of the coronary artery. A dine of 10% dehydrated alcohol in 0.2 ml for group A, a dose of isochoric lipoxin A4 for group B and a dose of isochoric ZnPP + lipoxin A4 for group C was infused into the ascending aorta through a catheter, which was kpassing the right common carotid artery, 30 minutes after reperfusion. The concentration of serum TNF-α, activities of serum crestine kinase(CK) and lactate dehydrogenase (LDH), activities of myeloperoxidase (MPO) and malond- ialdehyde (MDA) and the cell apoptosis rate in the myocardial tissue were measured 5 hours after reperfusion. Pathological features of the inflammatory infiltration in the myocardium were also observated.Results As compared with group A, the inflammatoryry infiltra- tion in the ischemic and necrotic regions tithe myocardium was reduced, with group C in the intermediate range. The serum activities of CK and LDH wine significantly lower in group B and C than that in group A, and the lowest activities were detected in group B. Similar findings were observed for MPO, an indicator for neutrophil infiltration, and MDA, an indictor for cell injury caused by oxy- gen radicals, in the myocardium. The concentration of TNF-α and the rate of cadiocyte apoptosis were decreased significantly in group B(P < 0.01). ZnPP, an inhibitor of heine oxygenase (HO)-1, attenusted the above protective effects of lipoxin A4 significantly (P<0.05). Conclusion Lipoxin A4 has protective effects against myocardial ischemia-reperfusion injury, and HO-1 may have a potential role in the protectve mechanisms of lipoxin A4, probably pertly by means of reducing the production of reactive oxygen spe- cies and TNF-α, decreasing the activation and infiltration of neutrophils, alleviating inflammatory damage and avoiding apoptosis.     

热休克蛋白70对缺血再灌注未成熟心肌间质的保护作用

目的观察热休克蛋白70在未成熟心肌中的表达及对缺血再灌注未成熟心肌间质的影响。方法①实验于2001-12/2002-06在华中科技大学同济医学院药理实验室完成。选用出生14～21d的健康新生长耳大白兔12只。随机将兔分为2组对照组和实验组,每组6只。②对照组腹腔注射生理盐水0.4m L,注射后24h取体外心脏,常规建立Langendorff体外心脏灌注模型,灌注15m in转为工作心15m in后停灌45m in,恢复灌注15m in改为工作心30m in;实验组腹腔注射重酒石酸去甲肾上腺素,24h后取体外心脏,方法同对照组。③采用蛋白印迹法测定心肌细胞中热休克蛋白70含量。按公式计算羟脯氨酸含量(样本A值/标准A值×10×稀释倍数×1/组织质量)。采用均相放射免疫竞争法直接测定血浆内皮素1水平。④计量资料差异比较采用t检验。结果兔12只均进入结果分析。①实验组心肌细胞中热休克蛋白70含量(A值)明显高于对照组(P<0.01)。②实验组兔心肌羟脯氨酸含量明显高于对照组(P<0.01),血清内皮素1水平明显低于对照组(P<0.01)。结论腹腔注射重酒石酸去甲肾上腺素诱导未成熟大白兔心脏热休克蛋白70表达,在注射24h后热休克蛋白70表达明显增多,热休克蛋白70可明显减轻未成熟心肌内皮素的释放和心肌胶原的降解。