慢性心力衰竭的免疫调节治疗进展

<正> 慢性心力衰竭作为大多数心血管疾病的最终转归,目前已有较为理想的内科治疗,但病死率和致残率仍然很高。由于改善血流动力学,逆转神经激素的激活,防止心室重构,治疗已取得重大突破,但仍不能完全控制其进行性发展。近年来研究表明,以淋巴细胞亚群数量的改变及炎性细胞因子升高为标志的免疫激活和炎性反应,在慢性心力衰竭进展过程中发挥着重要作用。人们由此开始探索慢性心力衰竭治     

麝香保心丸对心力衰竭大鼠Th1和Th2型细胞因子水平的影响

Objective To investigate the effects of Shexiangbaoxin pills (SXBXP) on the serum levels of T helper type 1 (Th1) cytokines including tumor necrosis factor-a (TNF-α),interferon-γ(IFN-γ) and T helper type 2 (Th2) cytokines incloding interleukin-4 (IL-4),interleukin-10 (IL-10)in rats with chronic heart failure (CHF).Methods The CHF models were established by left anterior descending coronary artery ligation.Fifty-four Wistar rats were randomly divided into six groups:control group,sham operation group,CHF model group,small dose SXBXP group,large dose SXBXP group and positive medicine group.Heart function was examined by echocardiography before and after therapy,the TNF-α and IL-10 levels were measured by radioimmunoassay,IFN-γ and IL-4 levels were measured by enzyme linked immunosorbent assay (ELISA).Results (1) Before therapy,there was no significant difference between control group and sham operation group in ejection fraction of left ventricle (LVEF).Compared with control group and sham operation group,the levels of LVEF were significantly decreased in CHF model group,small dose SXBXP group,large dose SXBXP group and positive medicine group (all P＜0.01).(2) After therapy,compared with sham operation group,the serum levels of TNF-α and IFN-γ were markedly increased,and IL-4 and IL-10 were significantly decreased in CHF model group (all P＜0.01 ).Compared with CHF model group,LVEF was significantly improved,serum levels of TNF-α and IFN-γ were markedly decreased,IL-4 and IL-10 were markedly increased in large dose SXBXP group (all P＜0.05).In small dose SXBXP group,serum levels of IFN-γ were markedly decreased and IL-10 were markedly increased (all P＜0.05).In positive medicine group,serum levels of TNF-α and IFN-γ were markedly decreased and IL-10 were markedly increased (all P＜0.05).In small dose SXBXP group and positive medicine group,serum levels of IL-4 increased and LVEF decreased,even though there was no significant difference compared with CHF model group.Conclusions The SXBXP therapy of rats with CHF induced by myocardial infarction improves the heart function,decreases the serum levels of TNF-α and IFN-γ,and increases serum levels of IL-4 and IL-10.     

奥美沙坦对心力衰竭大鼠肺脏肾上腺素能受体表达的影响

目的:研究奥美沙坦对心力衰竭大鼠肺脏α1A-肾上腺素受体(α1A-AR)和β1、β2肾上腺素受体(β-AR)表达水平及对血浆肾素活性(plasma rennin activity,PRA)和血管紧张素Ⅱ(angiotensinⅡ,AngⅡ)水平的影响。方法:45只Wistar大鼠随机分为正常对照组(A组)、假手术组(B组)、心力衰竭模型对照组(C组)和奥美沙坦组(D组),采用灌胃法给药。超声心动图检测用药前后大鼠心脏功能,灌胃治疗8 w后,腹主动脉取血,采用放射免疫法测定各组大鼠PRA、AngⅡ水平,取大鼠肺组织,采用蛋白质免疫印迹法(Western Blot)测定各组的α1A-AR、β1-AR和β2-AR的蛋白表达水平。超声心动图检测用药前后大鼠心脏功能。治疗8 w后,腹主动脉取血,采用放射免疫法测定各组大鼠PRA、AngⅡ水平,取大鼠肺组织,采用蛋白质免疫印迹法(Western Blot)测定各组的α1A-AR、β1-AR和β2-AR的蛋白表达水平。结果 :用药前A组与B组比较,大鼠左心室射血分数(LVEF)组间差异无统计学意义(P>0.05);与B组比较,C组、D组大鼠LVEF明显降低(均P<0.05)。用药后,与C组比较,D组LVEF显著改善(P<0.05)。用药后,A组与B组大鼠PRA、AngⅡ水平差异无统计学意义(P>0.05);与B组比较,C组大鼠PRA、AngⅡ水平明显升高(P<0.01);与C组比较,D组大鼠血浆PRA、AngⅡ水平明显降低(P<0.05);在蛋白质表达水平,A组与B组用药后比较,各受体水平差异无统计学意义(P>0.05)。与B组比较,C组大鼠α1A-AR、β1-AR表达水平显著下调(P<0.05),β2-AR表达水平明显上调(P<0.01);与C组相比,D组α1A-AR、β1-AR及β2-AR水平均显著升高(均P<0.05)。结论:奥美沙坦能够改善心肌梗死后心力衰竭大鼠的心脏功能,提高LVEF,同时能够降低心力衰竭时血浆中升高的PRA和AngⅡ,并使心力衰竭大鼠肺脏下调的α1A-AR、β1-AR上调,表达增加的β2-AR进一步上调。奥美沙坦对慢性心力衰竭(chronic heart failure,CHF)时交感-肾上腺素系统激活后肾上腺素受体表达的调节作用和对PRA、AngⅡ的抑制作用,有利于维持心力衰竭时肺脏的通气/血流比值,减轻肺水肿,改善心力衰竭时的肺循环淤血,对CHF的肺脏起到了有益的保护作用。     

112例左束支传导阻滞患者冠状动脉造影结果及临床特点分析

目的探讨左束支传导阻滞(LBBB)患者冠状动脉造影结果及临床特点。方法分析112例具有冠状动脉造影结果的LBBB患者的临床资料,冠状动脉至少1支主要分支管腔狭窄>50%为冠心病的诊断标准。结果 112例患者中,46例符合冠心病诊断标准(41.1%),其中24例为冠状动脉单支病变(52.2%),14例为冠状动脉2支病变(30.4%),8例为左主干病变或者3支病变(17.4%)。LVEF>40%的92例患者中,有左主干病变或者3支病变的仅为5例(5.4%);20例LVEF≤40%的患者中,则有3例(15.0%)为左主干病变或者3支病变。结论冠心病为LBBB的第1位病因,依次为高血压、糖尿病、扩张型心肌病及单纯LBBB;诊断为冠心病的LBBB患者中以冠状动脉单支病变为主,因此,冠心病的严重程度与LBBB没有直接关系。LBBB伴有左心室收缩功能不全的患者中左主干或者3支病变的发生率明显高于不伴有左心室收缩功能不全的患者。     

麝香保心丸对心力衰竭大鼠Th1和Th2型细胞因子水平的影响

Objective To investigate the effects of Shexiangbaoxin pills (SXBXP) on the serum levels of T helper type 1 (Th1) cytokines including tumor necrosis factor-a (TNF-α),interferon-γ(IFN-γ) and T helper type 2 (Th2) cytokines incloding interleukin-4 (IL-4),interleukin-10 (IL-10)in rats with chronic heart failure (CHF).Methods The CHF models were established by left anterior descending coronary artery ligation.Fifty-four Wistar rats were randomly divided into six groups:control group,sham operation group,CHF model group,small dose SXBXP group,large dose SXBXP group and positive medicine group.Heart function was examined by echocardiography before and after therapy,the TNF-α and IL-10 levels were measured by radioimmunoassay,IFN-γ and IL-4 levels were measured by enzyme linked immunosorbent assay (ELISA).Results (1) Before therapy,there was no significant difference between control group and sham operation group in ejection fraction of left ventricle (LVEF).Compared with control group and sham operation group,the levels of LVEF were significantly decreased in CHF model group,small dose SXBXP group,large dose SXBXP group and positive medicine group (all P＜0.01).(2) After therapy,compared with sham operation group,the serum levels of TNF-α and IFN-γ were markedly increased,and IL-4 and IL-10 were significantly decreased in CHF model group (all P＜0.01 ).Compared with CHF model group,LVEF was significantly improved,serum levels of TNF-α and IFN-γ were markedly decreased,IL-4 and IL-10 were markedly increased in large dose SXBXP group (all P＜0.05).In small dose SXBXP group,serum levels of IFN-γ were markedly decreased and IL-10 were markedly increased (all P＜0.05).In positive medicine group,serum levels of TNF-α and IFN-γ were markedly decreased and IL-10 were markedly increased (all P＜0.05).In small dose SXBXP group and positive medicine group,serum levels of IL-4 increased and LVEF decreased,even though there was no significant difference compared with CHF model group.Conclusions The SXBXP therapy of rats with CHF induced by myocardial infarction improves the heart function,decreases the serum levels of TNF-α and IFN-γ,and increases serum levels of IL-4 and IL-10.     

浅低温对心肌缺血-再灌注损伤合并脓毒症大鼠模型的心肌保护作用

目的:探究浅低温对心肌缺血-再灌注损伤合并脓毒症大鼠模型的心肌保护作用。方法:共15只SD大鼠随机分为心肌缺血-再灌注损伤合并脓毒症浅低温(MHT)组、心肌缺血-再灌注损伤合并脓毒症常温(NT)组和假手术常温组作为对照组。大鼠心肌缺血后再灌注同时给予内毒素,然后MHT组将大鼠置于冰床降温,15 min内达(33.0±0.5)℃,随后维持2 h。NT组及对照组实验全程维持在(37.0±0.5)℃。实验全程观察和记录血流动力学指标。浅低温或常温维持2 h后用酶联免疫吸附测定法检测血乳酸脱氢酶(LDH)、肌酸激酶同工酶(CK-MB),观察心肌梗死面积、病理学变化,免疫印迹法检测心肌烟酰胺腺嘌呤二核苷酸磷酸氧化酶2(NOX2),免疫组化检测心肌胱天蛋白酶-3(caspase-3)和肿瘤坏死因子-α(TNF-α)。结果:MHT组再灌注2 h心率较NT组降低[(396.63±39.93)次/min vs(.457.74±32.77)次/min,P<0.05];左心室最大收缩压升高[(129.14±34.05)mmHg vs.(85.63±14.74)mmHg,1 mmHg=0.133 kPa,P<0.05]。MHT组收缩期压力最大变化速率(+max dp/dt)、左心室舒张末期压力(LVEDp)和舒张期压力最小变化速率(-min dp/dt)再灌注2 h较NT组绝对值也有所增加,且均高于对照组,但差异无统计学意义。MHT组的LDH和CK-MB均较NT组显著降低[(1153.61±127.85)U/L vs(.2213.34±599.60)U/L,P<0.05;(1103.22±114.75)U/L vs(.1731.33±688.05)U/L,P<0.05]。心肌病理变化提示MHT组心肌坏死呈点状或灶状,心肌间质淤血程度轻且炎细胞浸润较少。NT组心肌出现水肿、灶状或片状坏死,心肌间质区淤血程度重及存在大量炎细胞浸润。此外,MHT组的心肌梗死面积比率明显小于NT组[(11.23±2.82)%vs.(19.25±4.45)%,P<0.05]。免疫印迹法显示,NOX2在MHT组中相对表达量较NT组减少,但差异无统计学意义(P>0.05)。MHT组的caspase-3相对表达量及TNF-α相对表达量均较NT组显著降低[(1.06±0.34)%vs.(3.27±0.67)%;(12.23±3.31)%vs(.31.14±1.69)%],差异均有统计学意义(P均<0.05)。结论:浅低温对心肌缺血-再灌注损伤合并脓毒症有心脏保护作用,可改善心功能,减少心肌梗死面积,减轻心肌损伤、炎症、氧化应激及凋亡。     

中国心脏重症镇静镇痛专家共识解读与更新要点

心脏重症病人需要个体化的镇静与镇痛策略,同时保持血流动力学的稳定。多种药物都可以达到镇静镇痛 的目标值,选择时需要根据患者潜在的病理生理、每个病人血流动力学弱项、需要的镇静镇痛的目标水平来综合选 用短程或长程的镇静镇痛策略。     

右美托咪啶在冠状动脉旁路移植围术期中作用效果的荟萃分析

目的评价右美托咪啶在冠状动脉旁路移植术(CABG)围术期中的作用效果。方法计算机检索Cochrane图书馆、Pub Med、EMBase、Highwire、Medline、CBM、CNKI、CSJD等中外生物医学数据库,收集关于右美托咪啶在CABG围术期中应用的随机对照试验。按Cochrane系统评价方法,评价所纳入研究的文献质量,提取有效数据后采用Rev Man 5.0软件进行Meta分析。结果纳入10项研究,共计562例患者。Meta分析显示,与对照组比较,右美托咪啶注射液治疗组患者机械通气时间明显减少(RR=–2.26,95%CI–4.44~–0.07,P=0.04),室性心动过速发生率明显降低(RR=0.21,95%CI 0.09~0.53,P=0.0009),谵妄发生率明显降低(RR=0.53,95%CI 0.29~0.98,P=0.04),而ICU时间(RR=–0.27,95%CI–0.56~0.02,P=0.06)、病死率(RR=0.77,95%CI 0.20~3.05,P=0.71)、心动过缓(RR=1.46,95%CI0.88~2.44,P=0.14)、低血压(RR=1.55,95%CI 0.98~2.46,P=0.06)、合并应用升压药物(RR=0.99,95%CI 0.56~1.76,P=0.98)及房颤(RR=0.82,95%CI 0.58~1.17,P=0.27)等方面两组比较差异无统计学意义。结论 CABG围术期应用右美托咪啶治疗可明显减少机械通气时间及室性快速性心律失常、谵妄的发生,且不增加并发症的发生率,可改善患者预后。