Network pharmacology and subsequent experimental validation reveal the synergistic myocardial protection mechanism of Salvia miltiorrhiza Bge.and Carthamus tinctorius L.

Objective:To reveal the molecular mechanism underlying the compatibility of Salvia miltiorrhiza Bge(S.miltiorrhiza,Dan Shen)and C.tinctorius L.(C.tinctorius,Hong Hua)as an herb pair through network pharmacology and subsequent experimental validation.Methods:Network pharmacology was applied to construct an active ingredient-efficacy target-disease protein network to reveal the unique regulation pattern of s.miltiorrhiza and C.tinctorius as herb pair.Molecular docking was used to verify the binding of the components of these herbs and their potential targets.An H9c2 glucose hypoxia model was used to evaluate the efficacy of the components and their synergistic effects,which were evaluated using the combination index.Western blot was performed to detect the protein expression of these targets.Results:Network pharmacology analysis revealed 5 pathways and 8 core targets of s.miltiorrhiza and C.tinctorius in myocardial protection.Five of the core targets were enriched in the hypoxia-inducible factor-1(HIF-1)signaling pathway.S.miltiorrhiza-C.tinctorius achieved vascular tone mainly by regulating the target genes of the HIF-1 pathway.As an upstream gene of the HIF-1 pathway,STAT3 can be activated by the active ingredients cryptotanshinone(Ctan),salvianolic acid B(Sal.B),and myricetin(Myric).Cell experiments revealed that Myric,Sal.B,and Ctan also exhibited synergistic myocardial protective activity.Molecular docking verified the strong binding of Myric,Sal.B,and Ctan to STAT3.Western blot further showed that the active ingredients synergistically upregulated the protein expressionof STAT3.Conclusion:The pharmacodynamic transmission analysis revealed that the active ingredients of S.miltiorrhiza and C.tinctorius can synergistically resist ischemia through various targets and pathways.This study provides a methodological reference for interpreting traditional Chinese medicine compatibility.

Research Progress on Myocardial Protection Strategies

Myocaridial protection aims to salvage myocardium from ischemia and reperfusion injury and to reduce infarct size and its consequences.After more than 30 years of development,the concept of ischemic preconditioning has evolved into"ischemic conditioning",a term that encompasses a number of related endogenous cardioprotective strategies,which can be applied either directly to the heart(ischemic preconditioning or postconditioning)or from afar,for example to a limb(remote ischemic preconditioning,preconditioning,or postconditioning).A variety of cardioprotective therapies have shown promising results in reducing infarct size and improving clinical outcomes in patients with ischemic heart disease.

Sevoflurane Versus Propofol for Myocardial Protection in Patients Undergoing Coronary Artery Bypass Grafting Surgery: a Meta-analysis of Randomized Controlled Trials

Objective To systematically review randomized controlled trials to compare myocardial protection profiles of sevoflurane with propofol in patients undergoing coronary artery bypass grafting （CABG） surgery. Methods Electronic databases were searched to identify all randomized controlled trials comparing sevoflurane with propofol for protecting myocardium in adult patients undergoing CABG surgery. Two authors independently extracted patients＇ perioperative data, including patients＇ baseline characteristics, surgical variables, and outcome data. For continuous variables, treatment effects were calculated as weighted mean difference （WMD） and 95% confidential interval （C/）. For dichotomous data, treatment effects were calculated as odds ratio （OR） and 95% CI. Each outcome was tested for heterogeneity, and randomized-effects or fixed-effects model was used in the presence or absence of significant heterogeneity （Q test P〈0.05）. Sensitivity analyses were done by examining the influence of statistical model on estimated treatment effects. Publication bias was explored through visual inspection of funnel plots of the outcomes. Statistical significance was defined as P〈0.05. Results Our search yielded 13 studies including 696 patients, and 402 patients were allocated into sevoflurane group and 294 into propofol group. There was no significant difference in postoperative mechanical ventilation time, inotropic support, mortality, myocardial infarction, and atrial fibrillation between the two groups （all P〉0.05）. Patients randomized into sevoflurane group had higher post-bypass cardiac index （WMD=0.39, 95% CI： 0.18 to 0.60, P=0.0003）, lower troponin I level （WMD=-0.82, 95% CI：-0.87 to -0.85, P=0.0002）, lower incidence of myocardial ischemia （OR=0.37, 95% CI： 0.16 to 0.83, P=0.02）, shorter ICU and hospital stay length （WMD=-10.99, 95% CI： -12.97 to -9.01, P〈0.00001; WMD=-0.78, 95% CI： -1.00 to -0.56, P〈0.00001, respectively）. Conclusion This meta-analysis has found some evidence showing that sevoflurane has better myocardial protection than propofol in CABG surgery.

Effects of Warm Blood Cardioplegic Solution on Myocardial Protection

To evaluate the effects of warm blood cardioplegic solution on myocardial protection, normothermic induction and terminal perfusion of oxygenated blood cardioplegia in combination with intermittent administration of cold blood cardioplegia during ischemia were studied in an isolated working rat heart model.The experimental protocol consisted of a 120 min cardioplegic arrest followed by 45 min normothermic reperfusion. Myocardial content of adenosine triphosphate (ATP), recovery of the left ventricular function, release of creatine phosphokinase (CPK) and ultrastructure of myocardium were assessed before and after ischemia. The results showed that the hearts preserved with warm blood cardioplegic induction and terminal perfusion had significantly higher levels of ATP,better recovery of cardiac function and lower releases of CPK than those receiving cold blood cardioplegia alone, with myocardial tissue being of generally normal structure. These findings suggest that warm induction and terminal perfusion of blood cardioplegic solution can accelerate myocardial metabolic and functional recovery, preserve high-energy phosphate, reduce myocardial injury and enhance myocardial protection.

Experimental and Clinical Research of Myocardial Protection Effect Using MHBC Perfusion

Objectives To determine themyocardium -protecting effect of medium hypothermalblood cardioplegia (MHBC); further demonstrates thatthe optimal temperature between these hypothermaland normothermic can overcome the disadvantages;and thus discovers a more effective myocardium pro-tecting method. Methods Section 1: 14 mongreldogs (15-20 kg) were randomly divided into twogroups: experimental group and control group; car-dialpulmonary bypass was conventionally instituted,moderate hypothermia blood cardioplegia was used inexperimental group, Blood samples from right atriumtaken for examination of lactate dehydrogenase (LDH)creatine kinase(CK-MB) and Topin Ⅰ(cTn-Ⅰ). speci-mens of left ventricular subendocardial myocardiumwere biopsied to observe changes of ultrastructure.Section 2: 24 patients were randomly divided into twogroups and both groups received two types of treat-ment (same as Section 1) after aorta cross-clamp(ACC). Biochemical index and Clinical observationwere caculated as the indicators. Results In the ex-perimental research, LDH, CK-MB, cTn-Ⅰ were foundincreased afer reperfusion in both groups, but the ex-tent of changes in experimental group is tiny (statisti-cal difference). Compared with control group the effectof MHBC on cardial function is litile; the ultrastruc-ture. of cardiac muscle has no obvious change. In theclinical research, compared the test results of venousblood drawn before CPB, after beating recovery andafter CPB, CBC perfused group (LDH, CK-MB leak-age and cTn-Ⅰ value increase.) compared with MHBCperfused group had no remarkable difference (P>0.05), but at the result of clinical observation: MHBCperfused group had red, soft hearts after cardiac arrestbut CBC perfused group had pale, spasmatic heartsafter cardiac arrest; 0 case in MHBC perfused groupand 3 cases in CBC perfused group had twitch-re-moving beat recovery; 11 cases in MHBC perfusedgroup and 3 cases in CBC perfused group recoveredsinus heart rhythm after surgery; average consumptionof lidocaine was 16.67 (±55.28) mg for MHBC per-fused group and 118.33(±82.65) mg for CBC perfusedgroup (P<0.01) afer surgery; 4 cases in MHBC per-fused group and 11 cases in CBC perfused group suf-fered arrhythmia after surgery. Conclusions As anew myocardium - protecting method, MHBC perfusionin combination with natural body temperature drop ofCPB is worth clinical dissemination and application.

Efficacy of electroacupuncture on myocardial protection and postoperative rehabilitation in patients undergoing cardiac surgery with cardiopulmonary bypass:a systematic review and Meta-analysis

OBJECTIVE:To evaluate the efficacy of electroacupuncture(EA)intervention on myocardial protection and postoperative rehabilitation in patients undergoing cardiac surgery with cardiopulmonary bypass(CPB).METHODS:Eight databases,including Pub Med,Embase,the Cochrane Library,Web of Science,Chinese Bio Medical Literature Database,China National Knowledge Infrastructure Database,Wanfang Data,China Science and Technology Journal Database,and two clinical trial registries,were searched.All randomized controlled trials(RCTs)related to EA intervention in cardiac surgery with CPB were collected.Based on the inclusion and exclusion criteria,two researchers independently screened articles and extracted data.After the quality evaluation,RevMan 5.3 software was used for analysis.RESULTS:Fourteen RCTs involving 836 patients were included.Compared with the control treatment,EA significantly increased the incidence of cardiac automatic rebeat after aortic unclamping[relative risk(RR)=1.15,95%confidence interval(CI)(1.01,1.31),P<0.05;moderate].Twenty-four hours after aortic unclamping,EA significantly increased the superoxide dismutase[standardized mean difference(SMD)=0.96,95%CI(0.32,1.61),P<0.05;low],and interleukin(IL)-2[SMD=1.33,95%CI(0.19,2.47),P<0.05;very low]expression levels and decreased the malondialdehyde[SMD=-1.62,95%CI(-2.15,-1.09),P<0.05;moderate],tumour necrosis factor-α[SMD=-1.28,95%CI(-2.37,-0.19),P<0.05;moderate],and cardiac troponin I[SMD=-1.09,95%CI(-1.85,-0.32),P<0.05;low]expression levels as well as the inotrope scores[SMD=-0.77,95%CI(-1.22,-0.31),P<0.05;high].There was no difference in IL-6 and IL-10 expression levels.The amount of intraoperative sedative[SMD=-0.31,95%CI(-0.54,-0.09),P<0.05;moderate]and opioid analgesic[SMD=-0.96,95%CI(-1.53,-0.38),P<0.05;low]medication was significantly lower in the EA group than in the control group.Moreover,the postoperative tracheal intubation time[SMD=-0.92,95%CI(-1.40,-0.45),P<0.05;low]and intensive care unit stay[SMD=-1.71,95%CI(-3.06,-0.36),P<0.05;low]were significantly shorter in the EA group than in the control group.There were no differences in the time to get out of bed for the first time,total days of antibiotic use after surgery,or postoperative hospital stay.No adverse reactions related to EA were reported in any of the included studies.CONCLUSIONS:In cardiac surgery with CPB,EA may be a safe and effective strategy to reduce myocardial ischaemia-reperfusion injury and speed up the recovery of patients after surgery.These findings must be interpreted with caution,as most of the evidence was of low or moderate quality.More RCTs with larger sample sizes and higher quality are needed to provide more convincing evidence.

Preliminary study on the protective effect of electroacupuncture Neiguan acupoint pretreatment on rats with myocardial ischemia-reperfusion injury:role of the miR-214-3p/NCX1 axis

Background:Ischemia-reperfusion can worsen myocardial damage and increase the risk of death.Studies have revealed that ischemic preconditioning provides the best endogenous protection against myocardial ischemia-reperfusion injury(MIRI),and the principle of electroacupuncture(EA)preconditioning is comparable to that of myocardial ischemic preconditioning adaption.Our earlier research demonstrated that EA pretreatment inhibits the expression of calmodulin-dependent protein kinase IIδ(CaMKIIδ),sodium/calcium exchanger 1(NCX1),and cyclophilin D,hence providing protection against MIRI.However,the exact mechanism is still unknown.The expression of NCX1 mRNA is directly regulated by microRNA-214(miR-214).Moreover,it suppresses the levels of CaMKIIδand cyclophilin D.Whether these variables contribute to EA preconditioning to improve MIRI needs to be investigated,though.This study aimed to preliminarily determine whether EA pretreatment ameliorates MIRI by modulating the miR-214-3p/NCX1 axis.Methods:We used a rat MIRI model to investigate the effect of EA pretreatment on MIRI and the expression of miR-214-3p.In addition,adenovirus injection inhibited miR-214-3p expression in the rat MIRI model,and the influence of EA pretreatment towards MIRI was observed in the context of blocked miR-214-3p expression.Both the myocardial histological abnormalities and the alterations in the ST segment of the rat electrocardiogram were analyzed.NCX1 mRNA,cyclophilin D,and CaMKIIδexpression levels were also analyzed.Results:EA pretreatment improved MIRI.In rats with MIRI,EA administration increased miR-214-3p expression while decreasing NCX1 mRNA,cyclophilin D,and CaMKIIδproteins in cardiac tissues.The beneficial effect of EA pretreatment against MIRI was reversed,coupled with elevated levels of NCX1 mRNA,cyclophilin D,and CaMKIIδprotein expression,when an adenovirus injection disrupted the expression of miR-214-3p.Conclusions:Our findings preliminarily show that EA pretreatment inhibits the expression of NCX1 mRNA,cyclophilin D,and CaMKIIδproteins via miR-214-3p,hence exerting MIRI protection.

MORPHOMETRIC EVALUATION ON MYOCARDIAL PROTECTION OF COLD CRYSTALLOID VERSUS WARM BLOOD CARDIOPLEGIA

Twenty patients undergoing open-heart valve replacement were divided randomly into two groups in this study; intermittent perfusion of cold crystalloid (St. Thomas Hospital solution) with hypothermic cardiopulmonary bypass (CPB) (hypothermic group) and continuous administration of warm blood cardioplegia with normothermic CPB (normothermic group) respectively. Tissue samples were taken from the right atrium before weaning from CPB and from the right appendage 30 minutes after removal of the cross-clamp. The results of pathological study in these two groups were as follows: the structural alterations were most severe during the ischemic period in the hypothermic group. Damages of the myocardial

Effect of a distal protection device on epicardial blood flow and myocardial perfusion in primary percutaneous coronary intervention

Objective: The beneficial effect of percutaneous coronary intervention (PCI) in patients with acute myocardial infarction (AMI) has been well established, but there is the problem of no-reflow phenomenon which is an adverse prognostic factor in primary PCI. In the present study the effect of a distal protection device (PercuSurge GuardWire; GW) on epicardial blood flow and myocardial perfusion was evaluated. Methods and Results: Patients with AMI were randomly divided into 2 groups, the GW and the control groups. The GW group included 52 patients with AMI who underwent primary PCI with GW protection and the control group included 60 patients who underwent primary PCI without GW protection. Epicardial blood flow in the infarct-related artery (IRA) and myocardial perfusion were evaluated according to the thrombolysis in myocardial infarction (TIMI) flow grade and the myocardial blush grade (MBG). We found TIMI score of 3 was obtained significantly more frequently in the GW group (96%) than in the control group (80%). The MBG score of 3 was obtained also significantly greater in the GW group (65%) than in the control group (33%). Conclusion: Primary PCI with GW protection can significantly improve epicardial blood flow and myocardial perfusion.

Myocardial Protection during Cardiac Surgery: Warm Blood versus Crystalloid Cardioplegia

Purpose: Prevention of myocardial injury is essential during cardiac surgery. Both crystalloid and blood cardioplegia are popular methods for myocardial protection. Most experimental studies have been in favor of blood cardioplegia. The objective of this study is to determine whether the use of warm blood cardioplegia (BCP) is superior to crystalloid cardioplegia (CCP) by means of myocardial injury markers and clinical outcome parameters. Materials and Methods: In a consecutive series of 293 patients, the first 150 received crystalloid cardioplegia, whereas the next 143 patients received blood cardioplegia. Postoperative myocardial injury was assessed by CTnI and CK-MB. Perioperative morbidity and mortality and clinical outcome parameters (need for inotropic support, ICU and hospital stay) were recorded. An unpaired student t-test was performed to analyse continuous postoperative variables relating to myocardial damage. The presence of possible confounders influencing the CTnI or CK-MB concentrations was tested using a student t-test for continuous variables, for categorical variables ANOVA was used. A final longitudinal model was created for CTnI and CK-MB. CTnI was analyzed by a mixed model with random intercept and slope. For all tests performed, statistical significance was 5%. Results: Both groups were well matched with respect to preoperative variables. No significant difference could be found in maximum postoperative levels of CTnI (8.8 ± 18.4 μg/l in BCP vs 9.6 ± 16.5 μg/l in CCP, p = 0.6455) or CK-MB (19.2 ± 31.0 μg/l in BCP vs 26.4 ± 41.5 μg/l in CCP, p = 0.1209). Nor was there any significant difference in other postoperative variables. Testing treatment effect over time proved only significant influence of the surgical intervention type on CTnI levels in time (p < 0.001). Conclusion: This study could not show significantly higher myocardial injury in the group of patients receiving crystalloid cardioplegia versus warm blood cardioplegia. This suggests that warm blood cardioplegia does not confer superior myocardial protection. Surgical intervention type has an important effect on CTnI concentration in time, while the type of cardioplegia does not.

阿芬太尼调节SphK1/S1P信号通路保护心肌缺血再灌注损伤大鼠

[目的]探究阿芬太尼对心肌缺血再灌注损伤(MIRI)大鼠的作用及在该过程中对鞘氨醇激酶1(SphK1)/鞘氨醇-1-磷酸(S1P)信号通路的调节机制。[方法]将SPF级SD雄性大鼠随机分为假手术组、模型组、阳性药物组(复方丹参组)和阿芬太尼低剂量组、阿芬太尼高剂量组、阿芬太尼高剂量+SphK1激动剂组(阿芬太尼+PMA组),每组20只。除假手术组,其余组均利用结扎左前降支冠状动脉后再灌注复制MIRI模型。全自动生物化学分析仪检测血清乳酸脱氢酶(LDH)、肌酸激酶(CK)和谷草转氨酶(AST)的活性;TTC检测大鼠心肌梗死面积;HE染色观察大鼠心肌组织形态学特征;TUNEL染色检测大鼠心肌细胞凋亡;ELISA检测血清肿瘤坏死因子α(TNF-α)、白细胞介素6(IL-6)、白细胞介素1β(IL-1β)及S1P的水平;试剂盒检测心肌组织中丙二醛(MDA)含量和超氧化物歧化酶(SOD)的活性;Western blot检测心肌组织SphK1蛋白表达。[结果]相较于假手术组,模型组大鼠心肌组织病理损伤严重,血清中心肌损伤标志物LDH、CK和AST的活性,心肌梗死面积和心肌细胞凋亡率,TNF-α、IL-6、IL-1β、MDA、S1P水平及SphK1蛋白表达均升高,SOD活性降低(P<0.05);相较于模型组,阳性药物组和阿芬太尼低、高剂量组大鼠心肌组织损伤减轻,血清中心肌损伤标志物LDH、CK和AST的活性,心肌梗死面积和心肌细胞凋亡率,TNF-α、IL-6、IL-1β、MDA、S1P水平及SphK1蛋白表达均降低,SOD活性升高(P<0.05)。SphK1激动剂可逆转高剂量阿芬太尼对上述指标的影响(P<0.05)。[结论]阿芬太尼对MIRI大鼠发挥保护作用,其机制可能与抑制SphK1/S1P信号通路有关。

天麻素在心肌缺血再灌注损伤中的作用机制和研究进展

缺血性心血管疾病是一种全球范围内高发的高病死率疾病,目前对于缺血及再灌注对脏器的损伤仍缺乏有效的治疗措施。天麻素作为一种多用于头痛惊厥的重要药物近年来被应用于心肌缺血再灌注损伤(MIRI)的保护治疗。MIRI的保护机制相关研究主要聚焦于细胞死亡、氧化应激、细胞自噬、炎症损伤、钙超载及微循环损伤等。以往临床研究证据表明,天麻素可通过调节细胞自噬作用影响MIRI多种损伤机制,同时,减少梗死面积及修复损伤功能。本文将近年最新有关天麻素和MIRI的文献进行高度凝练,并阐述天麻素在MIRI中发挥作用与调节自噬、恢复细胞稳态强密切相关,以期为临床应用天麻素保护MIRI提供重要的依据和方向。

阿芬太尼预处理通过抑制内质网应激发挥对心肌缺血再灌注损伤的保护作用

目的探究阿芬太尼预处理对心肌缺血再灌注损伤(myocardial Ischemia reperfusion injury,MIRI)大鼠的改善作用及可能存在的分子机制。方法纳入60只雄性SD大鼠,随机将其分为假手术组(Sham组,n=15)、模型组(MIRI组)、阿芬太尼低剂量预处理组(L-alfentanil组,3 mg/kg)及阿芬太尼高剂量预处理组(H-alfentanil组,6 mg/kg),每组15只;除去假手术组,剩余各组大鼠均构建MIRI模型。统计各组大鼠心功能参数[左心室舒张末期内径(LVEDD)、左心室收缩末期内径(LVESD)、左心室射血分数(LVEF)、左心室短轴缩短率(LVFS)]、血清心肌损伤因子[肌酸激酶同工酶(CK-MB)、肌钙蛋白Ⅰ(cTnI)]水平差异性;双染色法观察大鼠心肌梗死面积;HE染色分析心肌组织病理损伤;TUNEL检测心肌组织凋亡;免疫荧光及Western-blot检测各组大鼠心肌组织内质网应激蛋白(GRP78、CHOP、FAM134B)表达差异性。结果与Sham组相比,MIRI模型建立可以提升LVEDD、LVESD、CK-MB、cTnI水平、心肌梗死面积占比、心肌组织细胞凋亡程度及GRP78、CHOP表达及荧光强度,下调LVEF、LVFS水平及内质网应激蛋白FAM134B表达及荧光强度(P<0.05)。与MIRI组相比,阿芬太尼预处理可以下调LVEDD、LVESD、CK-MB、cTnI水平、心肌梗死面积占比、心肌组织细胞凋亡程度及GRP78、CHOP表达及荧光强度,上调LVEF、LVFS水平及内质网应激蛋白FAM134B表达及荧光强度(P<0.05)。与阿芬太尼低剂量组相比,阿芬太尼高剂量组大鼠LVEDD、LVESD、CK-MB、cTnI水平、心肌梗死面积占比、心肌组织细胞凋亡程度及GRP78、CHOP表达及荧光强度明显降低,LVEF、LVFS水平及内质网应激蛋白FAM134B表达及荧光强度明显提升,体现出剂量依赖性(P<0.05)。结论阿芬太尼预处理具有减轻心肌缺血再灌注大鼠心肌组织病理损伤,减少心肌梗死面积占比及抑制心肌组织细胞凋亡的作用,剂量依赖性明显,其分子机制可能与抑制内质网应激性程度有关,值得临床进一步研究。

右美托咪定辅助全身麻醉对老年非体外循环冠状动脉搭桥术患者血流动力学、心肌保护效应及术后转归的影响

目的探讨右美托咪定辅助全身麻醉对老年非体外循环冠状动脉搭桥术(CABG)患者血流动力学、心肌保护效应及术后转归的影响。方法前瞻性选取2021年6月至2023年6月邯郸市第一医院收治的110例非体外循环CABG患者,采用随机数字表法分为观察组和对照组,各55例。观察组给予右美托咪定辅助全身麻醉(麻醉诱导前15 min静滴0.6μg/kg,以0.2~0.4μg·kg^(-1)·h^(-1)持续泵注至手术结束),对照组给予等体积0.9%氯化钠溶液,其余同观察组。比较两组患者麻醉前(T_(0))、穿刺完毕5 min(T_(1))、手术结束即刻(T_(2))与手术后12 h(T_(3))的围手术期血流动力学指标[血氧饱和度(SpO_(2))与平均动脉压(MAP)、心率],手术前、手术后24、48 h的心肌损伤标志物[肌钙蛋白T(CTnT)和肌酸激酶同工酶(CK-MB)],手术前、手术后6、12、24 h的认知功能[蒙特利尔认知评估量表(MoCA)评分],术后转归情况(气管拔管、ICU滞留、苏醒、定向力恢复与术后住院时间)及躁动发生率。结果T_(0)时,两组SpO_(2)、MAP、心率比较,差异均无统计学意义(P>0.05);T_(1)、T_(2)、T_(3)时,观察组SpO_(2)、MAP、心率均高于对照组,差异均有统计学意义(P<0.05)。手术后24、48 h,观察组的cTnT和CK-MB水平均低于对照组,差异均有统计学意义(P<0.05)。手术后6、12、24 h,观察组的MoCA评分分别为(26.65±1.41)、(27.58±1.11)、(28.69±1.15)分,均高于对照组[(25.31±1.22)、(26.47±1.23)、(27.11±1.24)分],差异均有统计学意义(P<0.05)。两组苏醒时间、定向力恢复时间比较,差异均无统计学意义(P>0.05),观察组气管拔管时间、ICU滞留时间、术后住院时间分别为(15.86±3.36)h、(51.39±5.77)h、(11.39±2.48)d,均短于对照组[(19.75±3.41)h、(60.48±5.63)h、(13.65±2.61)d],差异均有统计学意义(P<0.05)。手术后6、24、48 h,观察组患者的躁动发生率分别为5.45%、3.64%、1.82%,均低于对照组(21.82%、16.36%、14.55%),差异均有统计学意义(P<0.05)。结论右美托咪定辅助全身麻醉在老年非体外循环冠脉搭桥术患者中可稳定患者围术期血流动力学,减少心肌损害,改善患者早期认知功能,同时可促进患者术后转归,降低术后躁动发生率。

基于TLR4/NF-κB/NLRP3信号通路探讨黄连解毒汤对冠状动脉性心脏病小鼠心肌保护作用

目的 研究基于Toll样受体4(TLR4)/核转录因子-κB(NF-κB)/NOD样受体蛋白3(NLRP3)信号通路探讨黄连解毒汤对冠状动脉粥样硬化性心脏病(CHD)小鼠心肌保护作用。方法 50只6周的雄性SD小鼠中取10只作正常对照组,其余小鼠给予高脂饮食建立CHD模型。采用随机数字表法将40只模型小鼠分为模型组、黄连解毒汤低、中、高剂量组,每组各10只。黄连解毒汤低、中、高剂量组每日分别以10、20、40 g/kg剂量进行灌胃,每日1次,持续6周;正常组、模型组每日给予等量蒸馏水灌胃。干预后采用生化法检测各组总胆固醇、甘油三酯、低密度脂蛋白(LDL)、高密度脂蛋白(HDL)水平,酶联免疫吸附试验检测超氧化物歧化酶(SOD)、丙二醛、内皮素水平;采用苏木精-伊红染色法观察小鼠心肌细胞病理形态,蛋白质印迹法检测心肌组织中TLR4、NF-κB、NLRP3的表达。比较各组小鼠血脂、心肌组织中抗氧化相关指标和TLR4、NF-κB、NLRP3的表达。结果 模型组、黄连解毒汤低、中、高剂量组血脂水平均高于对照组,差异均有统计学意义(P<0.05);黄连解毒汤低剂量组与模型组血脂水平比较,差异无统计学意义(P>0.05);黄连解毒汤中、高剂量组总胆固醇、甘油三酯、LDL水平均低于模型组,HDL水平高于模型组,差异均有统计学意义(P<0.05)。模型组、黄连解毒汤低、中、高剂量组心肌组织中SOD水平均低于对照组,丙二醛、内皮素水平均高于对照组,差异均有统计学意义(P<0.05);黄连解毒汤低、中、高剂量组SOD水平均高于模型组,丙二醛、内皮素水平均低于模型组,差异均有统计学意义(P<0.05)。对照组心肌纤维排列整齐,横纹清晰且细胞完整,无细胞肿胀、炎症浸润等;模型组心肌纤维排列紊乱,结构发生异常,有严重细胞肿胀、炎症浸润;黄连解毒汤低、中、高剂量组未见心肌纤维断裂,黄连解毒汤中、高剂量组细胞肿胀和炎症浸润情况优于黄连解毒汤低剂量组,黄连解毒汤高剂量组优于黄连解毒汤中剂量组。模型组、黄连解毒汤中、高剂量组TLR4、NF-κB、NLRP3蛋白表达量均高于对照组,差异均有统计学意义(P<0.05);黄连解毒汤低、中、高剂量组TLR4、NF-κB、NLRP3蛋白表达量均低于模型组,差异均有统计学意义(P<0.05)。且黄连解毒汤各剂量组中以上指标变化呈剂量依赖性。结论 黄连解毒汤能降低CHD小鼠血脂水平,保护心肌细胞,其能够通过下调组织TLR4、NF-κB、NLRP3蛋白表达以调节血脂水平并改善心肌功能,且黄连解毒汤的效果随着剂量的增加而增强。

瓜蒌皮注射液调控JNK/p38通路对缺氧/复氧诱导的心肌细胞损伤和凋亡的影响

目的探究瓜蒌皮注射液通过调节c-Jun N末端激酶/p38丝裂原活化蛋白激酶(JNK/p38)通路提高缺氧/复氧损伤条件下心肌细胞活力及抑制其凋亡的作用及可能机制。方法使用H9c2心肌细胞构建缺氧/复氧(H/R)模型,随后根据处理情况将细胞分为对照组、H/R组、H/R+瓜蒌皮组和H/R+瓜蒌皮+茴香霉素组。通过细胞计数试剂盒(CCK-8)检测各组细胞活力,试剂盒检测各组细胞中乳酸脱氢酶(LDH)、半胱天冬酶3(Caspase 3)活性;采用末端脱氧核苷酸转移酶介导的dUTP末端标记法(TUNEL)检测各组细胞凋亡并采用免疫印迹(WB)检测各组细胞中凋亡相关蛋白如B细胞淋巴瘤2(BCL-2)、BCL-2相关的X蛋白(BAX)、前半胱天冬蛋白3(Pro-caspase 3)、裂解的半胱天冬酶3(Cleaved-caspase 3)及JNK/p38通路蛋白表达。结果与对照组相比,H/R组的细胞活力显著降低,LDH和Caspase 3活性显著增加,细胞凋亡率升高,促凋亡蛋白BAX、Pro-caspase 3、Cleaved-caspase 3的表达上升,而抗凋亡蛋白Bcl-2的表达下降;同时,JNK/p38通路蛋白(JNK、p-JNK、p38、p-p38)的表达水平也显著升高,差异有统计学意义(P<0.05)。与H/R组相比,不同浓度的瓜蒌皮注射液处理后细胞活力均有所提升,尤其是2%瓜蒌皮注射液组表现出最佳效果(P<0.05)。与H/R组相比,H/R+瓜蒌皮组以及H/R+瓜蒌皮+茴香霉素组的细胞活力均显著升高,且两组的LDH和Caspase 3活性降低,细胞凋亡率及促凋亡蛋白(BAX、Pro-caspase 3、Cleaved-caspase 3)的表达下降,抗凋亡蛋白Bcl-2的表达上升,JNK/p38通路蛋白(JNK、p-JNK、p38、p-p38)的表达受到抑制(P<0.05)。与H/R+瓜蒌皮组相比,H/R+瓜蒌皮+茴香霉素组细胞活力受到抑制,LDH和Caspase 3活性升高;BAX、Pro-caspase 3、Cleavedcaspase 3及JNK、p-JNK、p38、p-p38的表达显著上升,而Bcl-2表达下降(P<0.05)。结论瓜蒌皮注射液能够通过抑制JNK/p38通路的激活增加细胞活力并减少细胞凋亡。

麝香保心丸联合人脑利钠肽对急性ST段抬高型心肌梗死患者的心肌保护作用及对动脉血流参数、ST2和IL-33的影响

目的:探讨麝香保心丸联合人脑利钠肽对急性ST段抬高型心肌梗死患者的心肌保护作用,以及对动脉血流参数、可溶性生长刺激表达基因2(ST2)和白细胞介素33(IL-33)的影响。方法:该前瞻性研究的研究时间为2021年3月至2023年3月,受试对象为105例急性ST段抬高型心肌梗死患者,共脱落5例,最后完成疗程并有完整记录的为100例。将100例患者采用随机数字表法分为研究组和对照组,每组50例。两组患者入院后均采取常规吸氧、心电监护等措施,立即建立静脉通路,并行经皮冠状动脉介入治疗;对照组患者采用注射人脑利钠肽进行治疗,研究组患者在对照组的基础上口服麝香保心丸,两组患者均连续治疗14 d。比较研究组与对照组患者治疗前后胸痛胸闷、心悸、气短、疲倦乏力、面肢浮肿和气喘等中医症状积分并比较疗效,比较研究组与对照组患者冠状动脉再通率,治疗前后心肌标志物水平、动脉血流参数以及血清ST2、IL-33、一氧化氮(NO)和内皮素-1(ET-1)水平变化。结果:治疗后,研究组患者胸痛胸闷、心悸、气短、疲倦乏力、面肢浮肿和气喘等各项中医症状积分较对照组更低,差异均有统计学意义(P<0.05)。研究组患者的治疗总有效率为96.00%(48/50),显著高于对照组的84.00%(42/50),差异有统计学意义(P<0.05)。治疗后,研究组患者血清N末端B型利钠肽前体、乳酸脱氢酶、心肌肌钙蛋白T和肌酸磷酸激酶含量较对照组更低;研究组患者冠状动脉再通率分级情况显著优于对照组;研究组患者左心室射血分数、左心室高峰充盈率、收缩期血流速度峰值、舒张期血流速度峰值和冠状动脉血流速度储备较对照组更高,左心室舒张末期内径较对照组更低;研究组患者血清ST2、IL-33和ET-1水平较对照组更低,血清NO水平较对照组更高,上述差异均有统计学意义(P<0.05)。结论:麝香保心丸联合人脑利钠肽对急性ST段抬高型心肌梗死患者的疗效较好,有助于保护心肌细胞,改善动脉血流循环,其心肌保护作用机制可能与减少ST2和IL-33的表达以及减轻血管损伤有关。

A型主动脉夹层术后急性心肌梗死相关危险因素的套索回归分析

目的探索A型主动脉夹层(TAAD)术后急性心肌梗死(PAMI)患者的危险因素并构建模型,以预测此类患者PAMI的风险。方法回顾性分析2018年1月至2022年10月,就诊于北京安贞医院并接受外科手术治疗TAAD患者的临床资料。以PAMI为终点,随机将这些患者的70%划分为训练集,剩余30%的患者划分为验证集。在训练集中应用套索(LASSO)回归探寻危险因素,构建模型,绘制列线图,并在验证集中验证模型的区分度和校准度。结果本研究共纳入1206例患者,83例(6.9%)患者发生终点事件。LASSO回归分析表明冠脉灌注不良、凝血酶原时间、纤维蛋白原降解产物、淀粉酶、手术时间、心肺转流时间对TAAD PAMI有较高的重要度。根据预测因子构建出的模型在训练集中区分度良好,一致性指数(C-index)为0.843,且模型的准确度较高。模型在验证集中的C-index为0.845。在预测的主要终点事件发生风险低于50%的患者中,校准曲线表明预测风险和观测风险基本一致。结论本研究形成的TAAD患者PAMI预测模型具有良好的区分能力,有助于临床医生早期干预PAMI的发生发展,进而提高TAAD患者临床预后。

心血管白塞氏病的体外循环管理

目的 总结心血管白塞氏病(CBD)患者行外科治疗的体外循环管理经验。方法 回顾性分析首都医科大学附属北京安贞医院2018年3月至2024年5月间行外科治疗的19例CBD患者的病例资料。结果 男性18例,女性1例,发病年龄在29~53岁之间。体外循环时间(180.53±95.12)min,主动脉阻断时间(122.74±41.63)min。心脏自动复跳8例,9例经电除颤后全部恢复自主心跳,全部患者体外循环过程顺利,安返ICU。术后1例患者发生低心排综合征死亡,其余患者恢复良好,顺利出院。结论 CBD患者再次手术几率高,手术难度大,对体外循环要求高,合适的体外循环管理可为手术提供重要保障。

线粒体酸5对阿霉素诱导的心肌细胞损伤的保护作用

目的探讨线粒体酸5(mitochonic acid 5,MA5)对阿霉素(doxorubicin,DOX)引起的心肌细胞损伤的保护机制。方法采用DOX处理的H9c2为细胞损伤模型,细胞分为:CON组(正常组)、DOX(1μmol/L DOX处理心肌细胞24 h)组、DOX+MA5组[1μmol/L DOX+MA5(1、5、10μmol/L)作用心肌细胞24 h]、CON+MA5(10μmol/L)组(10μmol/L MA5加入心肌细胞处理24 h)。免疫印迹法检测凋亡(Bax、Bcl-2、cleaved caspase3、cleaved caspase9)、焦亡(NLRP3、Caspase-1、IL-18)及炎症相关蛋白[核因子-κB(nuclear factor kappa B,NF-κB)、肿瘤坏死因子-α(tumor necrosis factor-α,TNF-α)、白细胞介素(interleukin,IL)-1β、IL-6]表达水平变化。结果与CON组相比,DOX组心肌细胞炎症相关蛋白(NF-κB,TNF-α,IL-1β,IL-6)表达上调,给予MA5(5、10μmol/L)处理后,炎症相关蛋白的表达受到明显抑制(P<0.05)。DOX组较CON组焦亡相关蛋白(NLRP3、Caspase-1、IL-18)表达量明显升高(P<0.05),而给予MA5(5、10μmol/L)处理后,焦亡相关蛋白的表达量明显减低(P<0.05),促凋亡蛋白表达量明显下降(P<0.05),抑制凋亡蛋白表达量上升(P<0.05)。结论MA5可能通过抑制DOX诱导的细胞炎症、焦亡和凋亡作用从而对DOX心脏毒性产生保护作用。