Effect of coenzyme Q10 supplementation on mitochondrial function after myocardial ischemia reperfusion.

BACKGROUND: Coenzyme Q10 (CoQ10) protects myocardium from ischemia-reperfusion (IR) injury as evidenced by improved recovery of mechanical function, ATP, and phosphocreatine during reperfusion. This protection may result from CoQ10's bioenergetic effects on the mitochondria, from its antioxidant properties, or both. The purpose of this study was to elucidate the effects of CoQ10 supplementation on mitochondrial function during myocardial ischemia-reperfusion using an isolated mitochondrial preparation. METHODS: Isolated hearts (n = 6/group) from rats pretreated with liposomal CoQ10 (10 mg/kg iv, CoQ10), vehicle (liposomal only, Vehicle), or saline (Saline) 30 min before the experiments were subjected to 15 min of equilibration (EQ), 25 min of ischemia (I), and 40 min of reperfusion (RP). Left ventricular-developed pressure (DP) was measured. Mitochondria were isolated at end-equilibration (end-EQ), at end-ischemia (end-I), and at end-reperfusion (end-RP). Mitochondrial respiratory function (State 2, 3, and 4, respiratory control index (RCI, ratio of State 3 to 4), and ADP:O ratio) was measured by polarography using NADH (alpha-ketoglutarate, alpha-KG)- or FADH (succinate, SA)-dependent substrates. RESULTS: CoQ10 improved recovery of DP at end-RP (67 +/- 11% in CoQ10 vs 47 +/- 5% in Vehicle and 50 +/- 11% in Saline, P < 0.05 vs Vehicle and Saline). CoQ10 did not change preischemic mitochondrial function. IR decreased State 3 and RCI in all groups using either substrate. CoQ10 had no effect in the mitochondrial oxidation of alpha-KG at end-I. CoQ10 improved State 3 at end-I when SA was used (167 +/- 21 in CoQ10 vs 120 +/- 10 in Saline and 111 +/- 10 ng-atoms O/min/mg protein in Vehicle, P < 0.05). Using alpha-KG as a substrate, CoQ10 improved RCI at end-RP (4.2 +/- 0.2 in CoQ10 vs 3.2 +/- 0.2 in Saline and 3.0 +/- 0.3 in Vehicle, P < 0.05). Using SA, CoQ10 improved State 3 (181 +/- 10 in CoQ10 vs 142 +/- 9 in Saline and 140 +/- 12 ng-atoms O/min/mg protein in Vehicle, P < 0.05) and RCI (2.21 +/- 0.06 in CoQ10 vs 1.85 +/- 0.11 in Saline and 1.72 +/- 0.08 in Vehicle, P < 0.05) at end-RP. CONCLUSIONS: The cardioprotective effects of CoQ10 can be attributed to the preservation of mitochondrial function during reperfusion as evidenced by improved FADH-dependent oxidation.     

缺血后适应对兔短期缺血再灌注心肌细胞凋亡的影响

目的探讨缺血后适应对兔局部短期缺血再灌注心肌细胞凋亡及Bcl-2、Bax蛋白表达的影响。方法18只新西兰白兔随机分成3组，每组6只；假手术对照组（S组）、缺血，再灌注对照组（IR组）、缺血后适应组（Post组）。除S组外，其余两组均接受左冠脉前降支15min阻断和30min再灌注，Post组在15min缺血后接受连续3次每次再灌注30s，缺血30s的后适应。以DNA电泳和TUNEL分析检测兔短期缺血再灌注心肌组织的细胞凋亡情况，免疫组织化学方法检测Bcl-2、Bax蛋白的表达。结果兔IR组缺血区心肌DNA电泳呈现DNA梯形，而Post组和s组未见梯形。Post组心肌细胞凋亡指数显著低于IR组[（28．06±2．92）％，（55．70±13．96）％，P〈0．01]。Bcl-2基因的蛋白表达量Post组高于IR组（10．00±0．89，7．83±1．47，P〈0．05）；Bax基因的蛋白表达量Post组低于IR组（7．50±0．84，9．83±0．98，P〈0．05）。结论缺血后适应显著减少了兔短期缺血再灌注诱导的心肌细胞凋亡程度与上调Bcl-2基因的蛋白表达，下调Bax基因的蛋白表达有关。     

线粒体钙单向转运体对大鼠脑缺血/再灌注损伤中线粒体能量代谢的影响

目的 探讨线粒体钙单向转运体(mitochondrial calcium uniporter,MCU)活动在大鼠脑缺血/再灌注损伤(ischemia/reperfusion injury,I/RI)中对能量代谢的影响. 方法 52只雄性Wistar大鼠按照完全随机法分为对照组(sham)、脑缺血/再灌注(ischemia/reperfusion,I/R)组、脑缺血/再灌注复合钌红(ischemia/reperfusion +ruthenium red,I/R+RR)组、脑缺血/再灌注复合精胺(ischemia/reperfusion+ spermine,I/R+Sper)组,线栓法建立大鼠大脑中动脉闭塞模型,缺血2h,再灌注24 h后检测脑梗死面积百分比,线粒体呼吸链酶复合体Ⅰ～Ⅳ活性、线粒体膜电位(mitochondrial membrane potential,△Ψm)、组织中三磷酸腺苷(adenosine triphosphate,ATP)含量和活性氧(reactive oxygen species,ROS)的含量. 结果 I/R组、I/R+RR组及I/R+Sper组的粒体呼吸链酶复合体Ⅰ～Ⅳ的活性(17.67±0.21)、(6.17±0.42)、(22.29± 1.40)、(31.73±0.84) nmol·mina·mg-1,△Ψm和组织中ATP的含量(5.2±60.19)nmol/mg protein均低于sham组(P＜0.01),而这3组的脑梗死面积百分比(35.43±0.74)％和ROS含量(1 455.21±39.52) U/mg protein高于对照组(P＜0.01).钌红能够改善上述指标:与I/R组比较,I/R+RR组中的钌红能够明显提高线粒体呼吸链酶复合体的活性(22.1±70.55)、(7.50±0.15)、(36.92±2,13)、(49.32 ± 1.33) nmol· min-1· mg-1,△ Ψm和组织中ATP的含量(7.85 ±0.17) nmol/mg protein(P＜0.01),明显缩小梗死面积(26.00 ±1.71)％,降低ROS的含量(1 262.53±29.92) U/mg protein (P＜0.01);而I/R+Sper组中的能量代谢指标则均较脑I/R组差. 结论 抑制MCU的活动可以明显改善I/RI中线粒体的能量代谢.     

Effects of ischemia and reperfusion injury on long-term graft function

Background

The clinical manifestation of ischemia/reperfusion injury in renal transplantation is delayed graft function (DGF), which is associated with an increase in acute rejection episodes (ARE), costs, and difficulties in immunosuppressive management. We sought to evaluated the DGF impact after renal transplant.

Methods

We evaluated a group of 628 patients undergoing deceased donor renal transplantation between 2002 and 2005 at 3 Brazilians institutions to define the main DGF characteristics.

Results

DGF incidence was 56.8%, being associated with elderly donors (P = .02), longer time on dialysis (P = .001), and greater cold ischemia time (CIT; P = .001). Upon multivariate analysis, time on dialysis >5 years increased DGF risk by 42% (P = .02) and CIT >24 hours increased it by 57% (P = .008). In contrast, DGF was associated with an higher incidence of ARE: 27.7% in DGF versus 18.4% in IGF patients (P = .047). The ARE risk was 46% higher among individuals with DGF (P = .02), 44% among patients >45 years old (P < .001), 50% among those with >5 years of dialysis time (P = .02), and 47% lower among the who were prescribed mycophenolate instead of azathioprine (P < .001). Patients with DGF showed worse 1-year graft function (54.6 ± 20.3 vs 59.6 ± 19.4 mL/min; P = .004), particularly those with ARE (55.5 ± 19.3 vs 60.7 ± 20.4; P = .009). One-year graft survival was 88.5% among DGF versus 94.0% among non-DGF patients.

Conclusion

The high incidence of DGF was mainly associated with a prolonged CIT. There was a relationship between DGF and ARE, as well as with a negative influence on long-term graft function.     

芬太尼后处理、肢体远隔缺血后处理和缺血后处理对大鼠心肌缺血/再灌注初期室性心律失常的影响

目的 对比观察芬太尼后处理、远隔缺血后处理和缺血后处理3种干预措施抑制大鼠心肌缺血/再灌注初期室性心律失常作用的差别.方法 将73只成年雄性SD大鼠(体重250 g～350 g)麻醉后按随机数字表法随机分为9组:空白对照组(S组,n=5);对照组(C组,n=7);芬太尼后处理组(F组,n=9);肢体远隔缺血后处理组(R组,n=9);缺血后处理组(P组,n=8);联合应用芬太尼后处理和肢体远隔缺血后处理组(F-R组,n=9);联合应用芬太尼后处理和缺血后处理组(F-P组,n=8);联合应用肢体远隔缺血后处理和缺血后处理组(R-P组,n=9);联合应用芬太尼后处理、肢体远隔缺血后处理和缺血后处理组(F-R-P组,n=9).所有大鼠开胸后采用丝线套扎其冠状动脉左前降支(left anterior descending coronary artery,LAD)做成活结.除S组之外,所有大鼠接受局部心肌缺血30 min和再灌注60 min的处理.C组不采用任何干预措施;F组、F-R组、F-P组和F-R-P组在LAD结扎15 min时缓慢静脉注射芬太尼30 μg/kg;R组、F-R组、R-P组和F-R-P组在LAD结扎15 min时结扎大鼠双下肢造成肢体缺血10 min后恢复双下肢血流灌注;P组、F-P组、R-P组和F-R-P组开放实施再灌注的初期连续实施3个循环的开放LAD 20 s/阻断LAD 20 s的缺血后处理.记录缺血期和再灌期前30 min内的心律失常评分(AS评分)以及室性心动过速(ventricular tachycardia,VT)和心室纤颤(ventricular fibrillation,VF)的发生率和持续时间.结果 缺血期VT和VF的发生率、VT或VF的持续时间以及AS评分在C组、F组、R组、P组、F-R组、F-P组、R-P组和F-R-P组无统计学差异.C组、F组、R组、P组、F-R组、F-P组、R-P组和F-R-P组再灌注初期AS评分的中位数分别为4、2、2、1、2、1、1和2.与C组比较,其余各组再灌注初期室性心律失常发生显著减少;再灌注初期的VT持续时间和AS在F组和R组之间无统计学差异,但F-R组再灌注初期的VT持续时间则显著降低.与F组和R组比较,P组、F-R组、F-P组、R-P组和F-R-P组再灌注初期的VT持续时间和室性心律失常评分显著减低. 结论 与芬太尼后处理和远隔缺血后处理比较,缺血后处理可更有效抑制再灌注初期室性心律失常的发生.联合应用芬太尼后处理和远隔缺血后处理后,抑制心肌再灌注初期室性心律失常的作用相对增强.     

右美托咪定预处理对大鼠心肌缺血-再灌注后心室功能和细胞凋亡的影响

目的探讨右美托咪定预处理对大鼠心肌缺血-再灌注损伤后心室功能和心肌细胞凋亡的影响。方法 30只SD大鼠随机分为三组,右美托咪定组(D组),右美托咪定+育亨宾组(D+Y组)和对照组(IR组),D组给予右美托咪定5μg·kg-1·h-1预处理1h,D+Y组静脉注射育亨宾1mg/kg,10min后按5μg·kg-1·h-1输注右美托咪定1h;IR组仅输注等量生理盐水,建立Langendorff缺血-再灌注模型,每10分钟测定左心室舒张末压(LVEDP)、左心室收缩压(LVSP)、左心室内压最大上升速率、下降速率(±dp/dtmax),计算左心室发展压(LVDP)。60min后取下心脏并以TUNEL检测心肌细胞的凋亡,RT-PCR检测Bcl-2mRNA,Bax mRNA的表达。结果与D组比较,再灌注后不同时点IR组和D+Y组大鼠LVDP、±dp/dtmax、Bcl-2mRNA表达明显降低、LVEDP、Bax mRNA表达明显升高(P0.05)。IR组和D+Y组LVDP、LVEDP、±dp/dtmax、Bcl-2mRNA和Bax mRNA表达差异均无统计学意义。IR组细胞阳性率为(36.1±9.2)%、D+Y组为(38.2±6.5)%,明显高于D组为(24.0±8.3)%(P0.05),而IR组和D+Y组细胞阳性率差异无统计学意义。结论右美托咪定预处理可以显著改善大鼠心肌缺血-再灌注损伤后的心室功能,并且可能通过调控凋亡基因Bcl-2mRNA和促凋亡基因BaxmRNA的表达,减少心肌细胞凋亡。     

Isovolemic hemodilution and skeletal muscle function during ischemia and reperfusion

Hemodilution has previously been shown to improve microcirculation in skeletal muscle after ischemia. We have studied the effects of isovolemic hemodilution with dextran on the function of anterior tibial muscle in the rabbit. Hemodiluted (hematocrit 28%) and nonhemodiluted animals were compared. Hemodilution led to an immediate increase in femoral blood flow. Flow normalized within 1–2 h, possibly due to flow redistribution. Hemodilution increased muscle force by 10%, which can reflect alterations in blood chemical composition or an improved microcirculation. Unilateral hindlimb ischemia induced by arterial occlusion inhibited muscle force to less than 15% in 150 min. Force and blood flow recovered almost completely after ischemia. After longer ischemia (170–300 min) when force was <5%, muscles did not recover. Hemodilution did not alter the muscle force or the extent or rate of force recovery after ischemia, which shows that the increased blood flow and improved microcirculation are not directly associated with changes in the sensitivity of muscle function to ischemia. © 1998 Wiley-Liss, Inc. MICROSURGERY 18:79-85 1998     

瑞芬太尼后处理对大鼠心肌缺血-再灌注损伤的影响

目的探讨瑞芬太尼后处理对缺血-再灌注心肌的影响及其机制。方法清洁级健康雄性SD大鼠78只,体重200~250g,随机分为六组:假手术组(S组)、单纯缺血-再灌注组(IR组)、纳洛酮拮抗剂组(NAL组)、瑞芬太尼5μg·kg~(-1)·min~(-1)后处理组(R1组)、瑞芬太尼10μg·kg~(-1)·min~(-1)后处理组(R2组)和瑞芬太尼20μg·kg~(-1)·min~(-1)后处理组(R3组),每组13只。S组仅在冠状动脉左前降支处穿线,但不结扎;IR组结扎冠状动脉左前降支,缺血45 min,再灌注24h;R1、R2和R3组在缺血35min时,分别静脉输注瑞芬太尼5、10和20μg·kg~(-1)·min~(-1),10min后再灌注24h;NAL组在心肌缺血25min时,静脉注射纳洛酮0.1mg·kg~(-1),10min后静脉输注瑞芬太尼10μg·kg~(-1)·min~(-1),10min后再灌注24h。观察心肌梗死面积和心肌病理学变化,同时测定血清肌钙蛋白I(cTnI)、乳酸脱氢酶(LDH)、肌酸激酶同工酶MB(CK-MB)的浓度。结果与S组比较,IR、NAL、R1、R2和R3组血清cTnI、LDH、CK-MB浓度明显升高,心肌梗死面积百分比明显增大(P0.05),心肌细胞损伤增多;与IR组比较,R1、R2和R3组血清cTnI、LDH、CK-MB浓度明显降低,心肌梗死面积百分比明显减小(P0.05),心肌细胞损伤减少(P0.05)。结论瑞芬太尼后处理可减轻大鼠心肌缺血-再灌注损伤,其机制与瑞芬太尼激活阿片受体有关,此作用具有量效"封顶"效应。     

Perioperative myocardial ischemia reperfusion injury

Myocardial I-R injury contributes to adverse cardiovascular outcomes after cardiac surgery. The pathogenesis of I-R injury is complex and involves the activation, coordination, and amplification of several systemic and local proinflammatory pathways (Fig. 4). Treatment and prevention of perioperative morbidity associated with myocardial I-R will ultimately require a multifocal approach. Combining preoperative risk stratification (co-morbidity and surgical complexity), minimizing initiating factors predisposing to SIRS, limiting ischemia duration, and administering appropriate immunotherapy directed toward systemic and local proinflammatory mediators of I-R injury, should all be considered. In addition, the role of the genetic-environmental interactions in the pathogenesis of cardiovascular disease is also being examined. Thus, in the near future, preoperative screening for polymorphisms of certain inflammatory and coagulation genes should inevitably help reduce morbidity by permitting the identification of high-risk cardiac surgical patients and introducing the opportunity for gene therapy or pharmacogenetic intervention [42,64].     

Coronary and systemic vascular resistance during reperfusion after global myocardial ischemia

During controlled aortic root reperfusion after global myocardial ischemia for the performance of coronary artery bypass grafting (N = 16), coronary blood flow was the highest during the first 1 minute to 2 minutes even though the aortic root pressure was controlled at about 40 mm Hg. Even during the period of controlled low pressure, flow began to decline, and the decline continued during the period in which the pressure was controlled at 75 mm Hg. Calculated coronary vascular resistance rose steadily from an initially low value to one well above the normal value for beating hearts. A transient fall in resistance resulted from the administration of a bolus of nitroglycerin into the aortic root. When the initial reperfusate was normokalemic, coronary flow was less and coronary vascular resistance higher during the initial phase of reperfusion. The systemic arterial pressure and resistance fell during the first 1 minute to 3 minutes of reperfusion and in 25% of patients, remained low. The greater the potassium load delivered during the initially hyperkalemic phase, the longer the interval between the beginning of reperfusion and the resumption of cardiac systole.     

Effects of in vivo myocardial ischemia and reperfusion on interstitial nitric oxide metabolites

BACKGROUND: There have been numerous studies examining the role of nitric oxide (NO) in myocardial ischemia-reperfusion injury; however, few studies have included measurements of NO or related reactive nitrogen species. The purpose of this study was to determine the effects of in vivo regional myocardial ischemia on interstitial fluid (ISF) reactive nitrogen species. METHODS: Open chest pigs were submitted to one of three protocols: (1) 15 minutes coronary occlusion and 2 hours reperfusion, (2) 60 minutes coronary occlusion and 2 hours reperfusion, or (3) two-cycle ischemic preconditioning (IPC) followed by prolonged ischemia and 2 hours reperfusion. The stable NO metabolites, nitrite plus nitrate (NOx), in cardiac microdialysis samples were measured by ozone chemiluminescence. RESULTS: NOx concentration decreased 40% +/- 6% (p < 0.05) during brief ischemia but returned to baseline during reperfusion. Dialysate NOx levels decreased further after 60 minutes ischemia (60% +/- 3% of baseline, p < 0.01) but reperfusion dialysate NOx concentration increased 34% +/- 9% above baseline (p < 0.05). Preconditioning did not increase dialysate NOx but did accelerate the ischemia-induced decrease in NOx levels (p < 0.05). Reperfusion NOx levels in preconditioned pigs were significantly lower than in nonpreconditioned pigs (p < 0.05). CONCLUSIONS: These results suggest that ischemia is associated with decreased ISF NOx concentration. Reperfusion NOx levels are increased after prolonged ischemia, an effect that is significantly blunted by ischemic preconditioning.     

线粒体钙单向转运体在二氮嗪预处理脑保护中的作用

目的探讨线粒体钙单向转运体是否参与了二氮嗪预处理所发挥的脑保护作用方法将52只健康雄性Wistar大鼠按照完全随机方法分为4组（每组13只）：A组,假手术组;B组,脑缺血厢獾注组;C组,脑缺血,再灌注＋二氮嗪组;D组,脑缺血,再灌注＋二氮嗪＋精胺组。采用线栓法建立大鼠大脑中动脉闭塞模型,缺血2h再灌注24h后观测各组神经行为变化,缺血侧脑组织线粒体钙含量及超氧化物歧化酶（superoxide dismutase,SOD）活性、丙二醛（malondialdehyde,MDA）含量、一氧化氮（nitric oxide,NO）含量和谷胱甘肽过氧化物酶（glutathione peroxidase,GSH-Px）活性。结果与B组比较,C组二氮嗪预处理可以改善大鼠脑缺血／再灌注引起的神经行为障碍（13．1±0．8,P〈0．01）,降低缺血侧脑线粒体钙含量（293±7）nmol／mgprot,（P〈0．05）,提高SOD（143±18）U／mgprot及GSH-Px（84±8）U／mgprot活性、降低MDA（0．799±0．092）nmol／mgprot,及NO（0．216±0．138）nmol／mgprot,含量（脚．05）。与c组比较,D组精胺可减弱二氮嗪预处理改善神经行为障碍（8．0±0．7,P〈0．01）、降低脑线粒体钙含量（322±10）nmol／mgprot,提高SOD（128±7）U／mgprot和GSH-Px（731-6）U／mgprot活性以及降低MDA（0．955±0．141）nmo]]mgprot,和NO（0．575±0．292）nmol／mgprot,含量的效应（P〈0．05）。结论二氮嗪预处理对抗大鼠脑缺血/再灌注损伤所发挥的脑保护效应,可能与其再灌注时减少线粒体钙单向转运体的活动以减少线粒体内钙含量及过氧化损伤有关。     

阿司匹林对小鼠心肌缺血/再灌注损伤时心肌组织炎症反应的影响

目的:研究阿司匹林对小鼠心肌缺血/再灌注损伤（myocardial ischemia/reperfusion injury, MI/RI）时心肌组织炎症反应的影响。方法:将60只雄性C57BL/6小鼠按随机数字表法分为3组（每组20只）：假手术组（S组）、缺血/再灌注（ischemia/reperfusion, I/R...     

尼可地尔预先给药对心肌缺血再灌注兔心肌细胞凋亡的影响

目的观察尼可地尔预先给药对心肌缺血再灌注兔心肌细胞凋亡的影响。方法 雄 性新西兰白兔40只,随机分为5组(n=8),假手术组(Sham组):仅穿线,不结扎;IR组:缺血30 min再 灌注120min;Nic组:缺血前10min静脉注射尼可地尔100μg·kg-1负荷量,随后以10μg·kg-1·min-1的 速率持续静脉输注至缺血前即刻;Nic 5-HD、Nic Gli组:在缺血前20 min静脉注射五羧基葵酸钠或 格列本脲5 mg·kg-1,其余的处理同Nic组。再灌注120 min时处死兔,计算心肌梗塞面积,通过两种染 色方法检测心肌细胞凋亡情况,观察心肌超微结构改变,并用免疫组织化学方法测定活化的caspase-3 蛋白表达。结果与IR组比较,Nic组心肌梗塞面积减小,早期凋亡细胞数减少,活化的caspase-3蛋 白表达下降(P<0．05),与Sham组比较,Nic组心肌仍有一定损伤,但较IR组明显改善。与Nic组比 较,Nic 5-HD、Nic Gli组心肌梗塞面积、早期凋亡细胞数、活化的caspase-3蛋白表达增加(P< 0．05)。结论尼可地尔预先给药对缺心肌血再灌注损伤有一定的保护作用,主要通过开放mito-KATPC 及下调活化的caspase-3蛋白的表达。     

Effects of intermittent reperfusion during temporal focal ischemia.

There is controversy regarding the role of intermittent reperfusion employed as a cerebroprotective measure when temporary arterial occlusion is necessary during repair of difficult aneurysms. The intraluminal suture middle cerebral artery (MCA) occlusion technique was used in 23 Wistar rats under barbiturate anesthesia to induce 60, 90, or 120 minutes of uninterrupted MCA occlusion. The total infarcted areas obtained were compared to those occurring in 27 animals subjected to identical cumulative ischemic periods but with 5 minutes of reperfusion after every 10-minute ischemic period. The mean total infarcted areas in the groups with 60-minute (1.8 +/- 0.89 sq mm), 90-minute (1.08 +/- 1.02 sq mm), and 120-minute (8.72 +/- 5.89 sq mm) intermittent reperfusion were significantly smaller than those occurring in the 60-minute (12.02 +/- 3.10 sq mm), 90-minute (11.54 +/- 2.68 sq mm), or 120-minute (30.43 +/- 6.51 sq mm) control groups, respectively (p < 0.05). Furthermore, there was no difference in the occurrence of blood-brain barrier breakdown, intraparenchymal hemorrhage, hemispheric edema, or seizures between control and intermittent reperfusion groups. The results support the hypothesis that intermittent reperfusion is beneficial if vessel occlusion is required during aneurysm repair.     

中性粒细胞与心肌缺血/再灌注损伤

背景 现已明确,炎症过程是心肌缺血/再灌注损伤(ischemia/reperfusion injury,I/RI)最重要的致病因素之一,而中性粒细胞是炎症反应的核心介导者.针对中性粒细胞的这种致病作用,部分研究者提出了抗中性粒细胞治疗,但是治疗效果却不尽相同,甚至大相径庭.更有研究者指出,中性粒细胞在心肌I/RI中尚发挥着一定的有益作用.针对这种现状,我们在此将中性粒细胞与心肌I/RI作一综述. 目的 评价中性粒细胞在心肌I/RI致病机制中的作用,探索抗中性粒细胞治疗的方向.内容 包括中性粒细胞对心肌I/RI的致病作用,抗中性粒细胞治疗的现状及其当前存在矛盾之处. 趋向 通过全面理解中性粒细胞在心肌I/RI中的作用,为今后进行适度的抗中性粒细胞治疗提供参考,并为今后发展多靶向联合措施治疗心肌I/RI提供思路.     

右美托咪定预处理对大鼠心肌缺血/再灌注损伤时心肌组织高迁移率族蛋白B1的影响

目的 探讨右美托咪定(dexmedetomidine,Dex)预处理对大鼠心肌缺血/再灌注损伤(myocardial ischemia/reperfusion injury,MFRI)时心肌组织高迁移率族蛋白B1(high mobility group box-1 protein,HMGB1)表达量的影响. 方法 健康雄性SD大鼠52只,体重250～300 g,按随机数字表法分为4组(每组13只):假手术组(S组)、缺血/再灌注(ischemia/reperfusion,I/R)组(I/R组)、Dex+I/R组(D组)、Dex+育亨宾+I/R组(D/Y组).结扎左冠状动脉前降支30 min,恢复灌注120 min制备MI/RI模型.再灌120 min时采血ELISA法测定血清中IL-6、TNF-α浓度,随后处死大鼠摘取心脏,用2,3,5-氯化三苯基四氮唑(2,3,5-triphenyltetrazolium chloride,TTC)染色法测定心肌梗死面积,Western blot法测定心肌组织HMGB1蛋白的表达量. 结果 与S组比较,I/R组血清中IL-6、TNF-α含量[(336±41)、(636±25) ng/L]均显著增高(P＜0.05),心肌梗死面积明显增大(P＜0.05),心肌组织HMGB1蛋白表达量明显升高(P＜0.05);与豫组比较,D组血清中IL-6、TNF-α含量[(153±10)、(233±9) ng/L]均明显降低(P＜0.05),心肌梗死面积明显减少(P＜0.05),心肌组织HMGB1蛋白表达量显著降低(P＜0.05);与D组比较,D/Y组血清中IL-6、TNF-α含量[(230±20)、(386±32) ng/L]均显著增高(P＜0.05),心肌梗死面积明显增大(P＜0.05),心肌组织HMGB1蛋白表达量明显升高(P＜0.05). 结论 Dex预处理减轻MI/RI心肌组织HMGB1的表达量,减轻I/R损伤的炎症反应.Dex通过α2受体发挥保护作用.