阿托伐他汀预处理对心肌缺血再灌注损伤大鼠心室重构、炎症反应和氧化应激的影响

目的:研究阿托伐他汀预处理对心肌缺血再灌注损伤大鼠心室重构、炎症反应和氧化应激的影响。方法:选取90只SD级大鼠进行研究,将其随机分成假手术组、缺血再灌注组、阿托伐他汀组,每组30只。假手术组与缺血再灌注组大鼠予以生理盐水(5 m L/d)连续灌胃7d处理,阿托伐他汀组予以阿托伐他汀20 mg/(kg·d)连续灌胃7 d,上述干预结束后,缺血再灌注组与阿托伐他汀组大鼠通过阻断大鼠冠状动脉左前降支的方式建立心肌缺血再灌注损伤模型。比较三组大鼠心室重构指标水平、炎症反应以及氧化应激相关指标水平。结果:缺血再灌注组、阿托伐他汀组大鼠的左室相对重量、右室相对重量、室间隔厚度、肿瘤坏死因子-α(TNF-α)、白细胞介素-1β(IL-1β)、丙二醛(MDA)、乳酸脱氧酶(LDH)水平均高于假手术组,且阿托伐他汀组大鼠上述指标均低于缺血再灌注组(均P<0.05);缺血再灌注组、阿托伐他汀组大鼠白介素-10(IL-10)、超氧化物气化酶(SOD)水平低于假手术组,且阿托伐他汀组大鼠IL-10、SOD水平高于缺血再灌注组(均P<0.05)。结论:阿托伐他汀预处理可有效预防心肌缺血再灌注损伤大鼠心室重构,同时可在一定程度上改善大鼠的炎症反应和氧化应激反应。     

NF-κB激活在兔急性心肌梗死再灌注后无复流中的意义

目的:观察心肌核因子-κB(NF-κB)在急性心肌梗死(AMI)再灌注后无复流的活化情况,探讨NF-κB促进无复流发生发展的作用机制。方法:24只新西兰大白兔随机分为假手术组(冠状动脉只穿线不结扎)和缺血再灌注组(结扎冠状动脉2小时,再灌注1小时),每组12只。采用凝胶阻滞迁移分析方法(EMSA)检测正常区、缺血区和无复流区心肌组织中NF-κB活性;ELISA法测定不同时点血浆中白细胞介素-6(IL-6)、超敏C反应蛋白(CRP)以及肿瘤坏死因子-α(TNF-α)的含量;光镜、电镜观察心肌组织病理变化。结果:(1)与正常区相比,缺血区和无复流区心肌组织中NF-κB活性异常升高(P<0.01)。(2)与结扎前相比结扎后2h、再灌注后1h血浆IL-6、CRP、TNF-α水平呈进行性升高(P均<0.05)。(3)NF-κB的活性与无复流面积、血浆IL-6、CRP以及TNF-α水平呈正相关(分别为r=0.844,P<0.01;r=0.682,P<0.05;r=0.687,P<0.05;r=0.893,P<0.01)。(4)无复流面积与血浆IL-6、CRP以及TNF-α水平呈正相关(分别为r=0.861,P<0.01;...     

不同剂量阿托伐他汀对老年急性冠脉综合征患者经PCI术后血清炎症因子水平和内皮功能的影响

目的:探讨不同剂量阿托伐他汀对老年急性冠脉综合征患者经PCI(经皮冠状动脉介入治疗,percutaneous coronary intervention)术后血脂、血清炎症因子水平及血管内皮功能的影响。方法:选取2015年8月至2017年4月我院收治的老年急性冠脉综合征患者80例,依据随机数据表法分为观察组和对照组,每组40例。对照组给予小剂量阿托伐他汀(20 mg/d)治疗,观察组给予大剂量阿托伐他汀(40 mg/d)治疗。比较两组治疗前后总胆固醇(total cholesterol,TC)、甘油三酯(triglyceride,TG)、低密度脂蛋白胆固醇(low-density lipoprotein,LDL-C)、高密度脂蛋白胆固醇(high-density lipoprotein,HDL-C)、超敏C反应蛋白(hypersensitive C-reactive protein,hs-CRP)、白介素-6(interleukin-6,IL-6)、肿瘤坏死因子(tumor necrosis factor-α,TNF-α)、一氧化氮(nitric oxide,NO)及内皮素-1(endothelin-1,ET-1)水平的变化。结果:治疗前,两组血清TC、TG、LDL-C、HDL-C、hs-CRP、IL-6、TNF-α、NO及ET-1水平比较差异均无统计学意义(P0.05);治疗后,两组血清TC、TG、LDL-C、hs-CRP、IL-6、TNF-α及ET-1水平与本组治疗前相比均显著性降低,且观察组治疗后血清TC、TG、LDL-C、hs-CRP、IL-6、TNF-α及ET-1的水平均显著低于对照组(P0.05);两组血清HDL-C、NO水平与治疗前相比均显著性升高(P0.05),且观察组治疗后的血清HDL-C、NO水平显著高于对照组(P0.05)。结论:阿托伐他汀用于经PCI术治疗的老年ACS患者可显著减轻再灌注后的炎症反应,降低血脂水平并改善内皮功能,且大剂量阿托伐他汀的治疗效果明显优于小剂量治疗。     

SPECT心肌灌注显像对急性心肌梗死患者PCI术后疗效评估

目的:探讨用单光子发射型计算机断层(single photon emission computedtomography,SPECT)心肌灌注显像,评估心肌梗死(AMI)经冠脉介入治疗(PCI)后的心肌灌注疗效。方法:采用99mTc-tetrofosmin(P53)SPECT心肌灌注显像对54例行PCI治疗的AMI患者评估心肌灌注情况,并追踪记录6个月内心脏事件发生率。结果:SPECT显示无复流组22例,有复流组32例,两组心肌梗死患者近期预后差异有统计学意义(P<0.05)。无复流组不良事件发生率较有复流组有增加趋势;另外,急诊PCI组的预后明显好于择期PCI组,差异有统计学意义(P<0.05)。结论:SPECT心肌灌注显像可对AMI患者梗死相关血管(IRA)再通治疗疗效进行可靠的无创性评价。     

NF-κ B激活在兔急性心肌梗死再灌注后无复流中的意义

目的：观察心肌核因子-κB（NF-κB）在急性心肌梗死（AMI）再灌注后无复流的活化情况,探讨NF-κB促进无复流发生发展的作用机制。方法：24只新西兰大白兔随机分为假手术组（冠状动脉只穿线不结扎）和缺血再灌注组（结扎冠状动脉2小时,再灌注1小时）,每组12只。采用凝胶阻滞迁移分析方法（EMSA）检测正常区、缺血区和无复流区心肌组织中NF-κB活性;ELISA法测定不同时点血浆中白细胞介素-6（IL-6）、超敏C反应蛋白（CRP）以及肿瘤坏死因子-α（TNF-α）的含量;光镜、电镜观察心肌组织病理变化。结果：（1）与正常区相比,缺血区和无复流区心肌组织中NF-κB活性异常升高（P〈0.01）。（2）与结扎前相比结扎后2h、再灌注后1h血浆IL-6、CRP、TNF-α水平呈进行性升高（P均〈0.05）。（3）NF-κB的活性与无复流面积、血浆IL-6、CRP以及TNF-α水平呈正相关（分别为r=0.844,P〈0.01;r=0.682,P〈0.05;r=0.687,P〈0.05;r=0.893,P〈0.01）。（4）无复流面积与血浆IL-6、CRP以及TNF-α水平呈正相关（分别为r=0.861,P〈0.01;r=0.806,P〈0.01;r=0.877,P〈0.01）。（5）光镜及电镜结果显示无复流区的心肌组织损伤较缺血区更为严重。结论：急性心肌梗死再灌注后无复流现象的发生可能与局部心肌组织中NF-κB的过度活化有关,活化的NF-κB通过促进IL-6、TNF-α等炎症因子的表达,参与无复流的发生发展过程。     

阿托伐他汀对肥胖家兔心房肌及心外膜脂肪中致心房颤动炎症因子的影响

目的:探讨肥胖家兔心外膜脂肪、血液、心房肌中致房颤炎症因子C反应蛋白(hs-CRP)、白细胞介素-6(IL-6)、白细胞介素-12(IL-12)、肿瘤坏死因子a(TNF-α)水平及阿托伐他汀的干预作用.方法:45只家兔随机分为普通饮食组(n=15)、肥胖饮食组(n=15)和阿托伐他汀干预组(n=15),肥胖饮食组预先给予高蛋白高脂饲料喂养4周制成肥胖模型(超重20％),肥胖组给予他汀喂养4周.ELISA法测定三组家兔血液、心肌、心外膜脂肪hs-CRP、IL-6、IL-12、TNF-α的水平.比较普通组、肥胖组、他汀干预组hs-CRP、IL-6、IL-12、TNF-α的水平,并进行统计学分析.结果:①肥胖组血清、心房肌、心外膜脂肪hs-CRP、IL-6、IL-12、TNF-α.的水平均高于普通组(P＜0.05);心房肌、心外膜脂肪中hs-CRP、IL-6、IL-12、TNF-α的水平均明显高于血液(P＜0.05).②肥胖他汀干预组血清、心房肌、心外膜脂肪hs-CRP、IL-6、IL-12、TNF-α的水平均低于肥胖组(P＜0.05).结论:肥胖可导致促房颤炎症因子的表达升高,心外膜脂肪中炎症因子表达高于心房肌,心房肌中炎症因子表达高于血液,心外膜脂肪组织可能是促房颤炎性因子的来源,参与了房颤的发生、发展,可能为始动环节,肥胖患房颤风险增高,阿托伐他汀可降低这种危险.     

围术期阿托伐他汀强化治疗对急性ST段抬高型心肌梗死患者Lp-PLA2与炎症因子的影响

目的:探讨阿托伐他汀强化治疗对急性ST段抬高型心肌梗死患者经皮冠状动脉介入治疗术后脂蛋白相关磷脂酶A2及炎症因子的影响。方法:选取98例行急诊经皮冠状动脉介入治疗术的急性ST段抬高型心肌梗死患者作为研究对象,随机分为A组和B组,各49例。A组患者术前顿服阿托伐他汀40 mg,术后继续口服阿托伐他汀40 mg/24 h;B组患者术前顿服阿托伐他汀20mg,术后继续口服阿托伐他汀20 mg/24 h。比较两组患者在治疗前后的脂蛋白相关磷脂酶A2(Lp-PLA2)、白细胞介素(IL)-6/肿瘤坏死因子(TNF)-α、丙氨酸转氨酶(ALT)及天冬氨酸转氨酶(AST)等炎症因子的水平。结果:治疗前两组患者的Lp-PLA2、IL-6、TNF-α、ALT及AST等因子水平的差异均无统计学意义(P0.05);治疗后,两组患者的Lp-PLA2、IL-6、TNF-α、ALT及AST等因子水平均高于治疗前(P0.05),且A组患者的Lp-PLA2、IL-6及TNF-α因子水平明显低于B组(P0.05),两组患者ALT、AST的水平无统计学差异(P0.05)。结论:围术期阿托伐他汀强化治疗能显著降低急性ST段抬高型心肌梗死患者的炎症因子水平与稳定斑块,疗效显著。     

缬沙坦联合阿托伐他汀钠对尿毒症维持性血液透析患者炎症因子及营养状况的影响

目的:探讨缬沙坦联合阿托伐他汀钠对维持性血液透析患者炎症因子及其营养状况的影响.方法:将120例维持性血液透析患者随机分为对照组与观察组,每组各60例.给予对照组患者口服阿托伐他汀,观察组患者给予缬沙坦联合阿托伐他汀钠口服.比较两组治疗前后C-反应蛋白(CRP)、IL-6、肿瘤坏死因子(TNF-α)、抵抗素及血清白蛋白(ALb)、血红蛋白(Hb)的变化情况.结果:治疗后6月两组患者hs-CRP、TNF-α、IL-6及抵抗素水平均显著下降(P＜0.05),但观察组患者上述指标显著低于对照组(P＜0.05);观察组治疗后Alb及Hb水平显著高于对照组,差别具有统计学意义(P＜0.05).结论:缬沙坦联合阿托伐他汀钠用于维持性血液透析患者,可显著减少炎症因子水平,改善患者营养状况.     

阿托伐他汀联合双抗血小板治疗对脑梗死患者疗效及对血清炎性因子水平的影响

目的:观察阿托伐他汀联合双抗血小板治疗对脑梗死患者脑血管事件复发率、神经功能缺损、血清炎性因子水平的影响,探讨其疗效和安全性。方法:选择2014年6月到2016年6月我院收治的脑梗死患者110例,按照随机数字表分为实验组和对照组,每组55例。两组患者均接受脑梗死常规治疗,对照组服用阿托伐他汀和阿司匹林,实验组服用阿托伐他汀、阿司匹林和氯毗格雷。在治疗前和治疗后2周、4周分别采用美国国立卫生研究院卒中量表(NIHSS)对患者神经功能缺损程度进行评分,检测血清炎性因子白细胞介素-6(IL-6)、白细胞介素-8(IL-8)和肿瘤坏死因子-α(TNF-α)水平,随访4周并统计脑血管事件复发率。结果:两组患者治疗2周、4周后NIHSS评分均低于治疗前(P0.05),且实验组低于对照组(P0.05)。两组患者治疗2周、4周后血清IL-6、IL-8和TNF-α均低于治疗前(P0.05),治疗4周后,实验组血清IL-6、IL-8和TNF-α水平均明显低于对照组(P0.05)。实验组患者脑血管事件复发率低于对照组,但差异无统计学意义(P0.05)。结论:阿托伐他汀联合双抗血小板疗法具备一定的抗炎作用,有助于脑梗死患者神经功能缺损恢复,且脑血管事件复发率低,值得临床推广应用。     

阿托伐他汀对冠心病大鼠心肌细胞的凋亡及caspase-12表达的影响

目的:探讨阿托伐他汀对冠心病大鼠心肌细胞的凋亡及caspase-12表达的影响。方法:21只清洁剂SD大鼠经高脂饮食冠心病造模成功后随机分为空白组、对照组和阿托伐他汀组每组7只。空白组大鼠未经处理,对照组给予生理盐水10 m L/kg体重灌胃,1天一次连续4周;阿托伐他汀组大鼠给予阿托伐他汀10 mg/kg体重灌胃,1天一次连续4周。4周后处死大鼠并取大鼠心肌组织采用TUNEL法检测细胞凋亡情况,Western-blot法检测caspase-12表达情况。结果:三组大鼠心肌凋亡比较空白组、对照组及阿托伐他汀组大鼠细胞凋亡比例分别为(3.72±0.89)%、(3.84±1.01)%和(1.47±0.62)%,阿托伐他汀大鼠心肌细胞凋亡比例明显低于空白组和对照组(P0.05);阿托伐他汀组大鼠心肌细胞Caspase-12表达水平显著低于空白组与对照组(P0.05),而空白组与对照组比较无统计学差异(P0.05)。结论:阿托伐他汀可能通过抑制大鼠心肌细胞caspase-12表达来阻断心肌细胞凋亡途径的激活。     

Myoglobin concentration and the state of myocardial organelles following myocardial infarction]

A study was made of the quantitative changes in myoglobin and the subcellular organization of the myocardium at early periods of experimental infarction of the heart in dogs. There proved to be a correlative relationship between the myoglobin content and the state of subcellular organization of the cardiomyocytes in the ischemic area and the so-called intact portions of the right and the left ventricles.     

Two-dimensional analysis of myocardial protein expression following myocardial ischemia and reperfusion in rabbits

Myocardial ischemia and reperfusion injury (MI/R) can be related to leukocyte activation with subsequent release of cytokines and oxygen derived free radicals. Activation of the complement system has been implicated in the pathogenesis of myocardial ischemia and reperfusion injury. Inflammatory injury will subsequently result in cellular activation and protein synthesis. In the present study we analyzed the myocardial protein expression and its pattern following myocardial ischemia and reperfusion, with and without complement inhibition with the synthetic serine protease inhibitor Futhan/nafamstat mesilate (FUT-175) known to inhibit classical and alternative complement pathway in a rabbit model of myocardial ischemia and reperfusion (60 min I+180 min R). FUT-175 significantly reduced myocardial necrosis, i.e. creatine kinase release which were analyzed for the three groups (p<0.05). Similarly, histological analysis demonstrated preservation of myocardial tissue injury and reduced leukocyte accumulation following FUT-175 treatment. Further, the myocardial protein expression was analyzed by two-dimensional gel electrophoresis following MI/R in the different groups. The protein patterns were evaluated by means of MELANIE III, a computer assisted gel analysis system. The biochemical identification of the proteins of interest was, achieved using nanohigh-performance liquid chromatography/electrospray ionization-tandem mass spectrometry. On average, 509 +/- 25 protein spots were found on the gels. A pattern of 480 spots with identical positions was found on every gel of five animals of each group. We analyzed ten spots which were significantly altered (i.e., in eight spots we observed decreased protein expression and in two spots we observed increased expression, vehicle vs. sham), by using mass spectrometry. Superoxide dismutase precursor and alphaB-crystallin were identified. We compared sham group vs. vehicle group and vehicle group vs. FUT-175 treated animals. Expression of the two identified proteins decreased by half the amount in the vehicle group when compared to sham treated animals. Treatment with FUT-175 preserved significantly superoxide dismutase precursor and alphaB-crystallin protein expression when compared to vehicle animals. The results present marked differences in myocardial protein expression after ischemia and reperfusion and following treatment with the complement inhibitor FUT-175. Our results illustrate the application of proteomics to discover possible new therapeutic targets or to detect unexpected effects of pharmacological inhibitors.     

脑钠肽及心肌活动指数在急性心肌梗死中的研究进展

脑钠肽(B type natrinretic peptides BNP)主要由心脏分泌的循环激素,具有扩血管利钠利尿抑制肾素醛固酮分泌的作用.急性心肌梗塞早期BNP即明显升高,对急性心肌梗塞患者预后有很好的指导作用;心肌活动指数(myocardial performance indexMPI)因不受超声条件、心脏几何形态、心室收缩及舒张压等影响,较之传统左室射血分数更为客观、准确,已被广泛应用于评价心功能.脑钠钛作为神经内分泌激素,心肌活动指数作为机械因素联合用于评价急性心肌梗死患者的预后及筛检急性冠脉事件的高危患者将起到更加重要的作用,本文现将两项指标在AMI最新研究进展作一综述.     

Mechanics of the left ventricular myocardial interstitium: effects of acute and chronic myocardial edema

Myocardial interstitial edema forms as a result of several disease states and clinical interventions. Acute myocardial interstitial edema is associated with compromised systolic and diastolic cardiac function and increased stiffness of the left ventricular chamber. Formation of chronic myocardial interstitial edema results in deposition of interstitial collagen, which causes interstitial fibrosis. To assess the effect of myocardial interstitial edema on the mechanical properties of the left ventricle and the myocardial interstitium, we induced acute and chronic interstitial edema in dogs. Acute myocardial edema was generated by coronary sinus pressure elevation, while chronic myocardial edema was generated by chronic pulmonary artery banding. The pressure-volume relationships of the left ventricular myocardial interstitium and left ventricular chamber for control animals were compared with acutely and chronically edematous animals. Collagen content of nonedematous and chronically edematous animals was also compared. Generating acute myocardial interstitial edema resulted in decreased left ventricular chamber compliance compared with nonedematous animals. With chronic edema, the primary form of collagen changed from type I to III. Left ventricular chamber compliance in animals made chronically edematous was significantly higher than nonedematous animals. The change in primary collagen type secondary to chronic left ventricular myocardial interstitial edema provides direct evidence for structural remodeling. The resulting functional adaptation allows the chronically edematous heart to maintain left ventricular chamber compliance when challenged with acute edema, thus preserving cardiac function over a wide range of interstitial fluid pressures.