不同剂量氯吡格雷联合阿司匹林在CYP2C19基因即时检测下对HR-NICE患者的疗效研究

目的 探讨不同剂量氯吡格雷联合阿司匹林在即时检测(point-of-care testing, POCT)细胞色素P-450 2C19(CYP2C19)基因型精准指导下治疗高危非致残性缺血性脑血管事件(high-risk non-disabling ischemic cerebrovascular events, HR-NICE)的疗效。方法 采用单中心、随机、前瞻、盲法评估。在2021年3月～2022年1月于徐州市中心医院脑卒中绿色通道及神经内科病房连续纳入HR-NICE患者,刮取颊黏膜行POCT筛选CYP2C19功能缺失等位基因携带者,按照随机数字表法分为强化组(氯吡格雷150mg/d)和常规组(氯吡格雷75mg/d)均联合阿司匹林(100mg/d)双重抗血小板治疗21天。收集两组患者的一般基线资料、急性脑卒中Org 10172 治疗试验(TOAST)分型及90天改良Rankin量表(mRS)评分、不良事件及严重不良事件发生等情况。主要疗效结局为90天内新发脑卒中,主要安全结局为90天内严重或中度出血。结果 共筛查1301例HR-NICE患者,携带CYP2C19功能缺失等位基因727例,符合纳入标准的476例:强化组236例,常规组240例。两组患者基线比较,差异均无统计学意义(P＞0.05);两组90天新发脑卒中强化组4例(1.7%),常规组26例(10.8%),两组比较差异有统计学意义(χ2=16.827,P<0.001);两组90天中重度出血强化组0例,常规组1例(2.5%),两组比较差异无统计学意义(P>0.05)。结论 对于CYP2C19功能缺失等位基因的HR-NICE患者,在抗血小板药物阿司匹林联合氯吡格雷的治疗中,强化氯吡格雷剂量的有效性优于常规剂量,且其安全性一致,未发生更多的出血等不良事件。     

缝隙连接蛋白43在老年大鼠缺血性室性心律失常中的作用

Objective To investigate the expression of connexin43 ( Cx43 ) and effect of vagal nerve stimulation (VNS) on ventricular tachyarrhythmias during acute myocardial ischemia( MI )in aged rats. Methods Male Sprague-Dawley rats[Adult group ( ≤ 4 months) and Aged group ( ≥24 months)]:MI (n = 15 ):ligated left anterior descending coronary for 30 minutes; MI-vagal nerve stimulation(VNS) ( n = 15 ); MI-VNS-atropine (0. 5 mg/kg, n = 13 ); MI-VNS-carbenoxolone ( 10 mg/kg, n = 11 ); sham operation (SO, n = 10):without coronary ligation. Ventricular arrhythmias were monitored by an electrocardiogram. Cx43 protein expression was analyzed by Western blot. Results During the 30 minutes ligation,incidences of ventricular tachycardia (VT) and ventricular fibrillation(VF) in aged rats increased significantly compared to those of adult rats ( P ＜ 0. 05 ). VNS did not affect the occurrence of VT and VF ( both P ＞ 0.05 ); however, VNS suppressed the occurrence of irreversible VF ( P ＜ 0. 05 ); both atropine and carbenoxolone ( a gap junction inhibitor) could abolish the effect of VNS on ischemia-induced irreversible VF ( both P ＜0. 05). Ischemia did not result in changes of total Cx43 amount in adult and aged rats compared to that of SO group,respectively. The amount of nonphosphorylated Cx43 was increased markedly in adult and aged rats compared to that of SO group,respectively.Cx43 dephosphorylation induced by ischemia was significantly suppressed by VNS in adult and aged rats( P ＜0. 05 ). However,the amount of total Cx43 of SO group in aged rats was significantly decreased by 50% compared to that of SO group in adult rats ( P ＜ 0. 05 ). Conclusion The present study suggested that the incidence of ischemia-induced ventricular tachyarrhythmias increased markedly and the anti-arrhythmic effect of VNS was decreased significantly in aged rats, which may be associated with reduction of Cx43 protein of ventricle in aged rats.     

缝隙连接蛋白43在老年大鼠缺血性室性心律失常中的作用

目的 探讨缝隙连接蛋白43(Cx43)在老年大鼠心室肌中的表达及急性心肌缺血时迷走神经刺激对老年大鼠缺血性室性心律失常的影响.方法 结扎大鼠冠状动脉前降支制备急性心肌缺血模型,随机分为(1)成年组:假手术组(SO,n=10)、心肌缺血组(MI,n=15)、心肌缺血+迷走神经刺激组(MI-VNS,n=15)、心肌缺血+迷走神经刺激+阿托品(0.5 mg/kg)组(MI-VNS-Atr,n=13)和心肌缺血+迷走神经刺激+生胃酮(10 mg/kg)组(MI-VNS-CBX,n=11).(2)老年组:假手术组(SO,n=10)、心肌缺血组(MI,n=15)、心肌缺血+迷走神经刺激组(MI-VNS,n=15)、心肌缺血+迷走神经刺激+阿托品(0.5 mg/kg)组(M1-VNS-Atr,n=13)和心肌缺血+迷走神经刺激+生胃酮(10 mg/kg)组(MI-VNS-CBX,n=11).心电图监测室性心律失常的发生.Western blot分析Cx43蛋白表达变化.结果 结扎冠状动脉30 min内,老年MI组室性心动过速(室速)和心室颤动(室颤)发生率较成年MI组显著增加(P＜0.05);老年MI-VS组室速和室颤发生率与老年MI组相比差异无统计学意义(P＞0.05),但老年MI-VS组不可逆性室颤发生率较老年MI组明显减少(P＜0.05).冠状动脉结扎30 min后,缺血没有引起成年组和老年组的总Cx43含量改变(P＜0.05);但缺血引起成年组和老年组的非磷酸化Cx43含量明显增加,迷走神经刺激能够明显抑制成年组和老年组中缺血引起的Cx43脱磷酸化(P＜0.05);而阿托品和生胃酮明显阻断了迷走神经刺激抑制缺血引起的Cx43脱磷酸化的作用(P＜0.05).但实验发现老年SO组Cx43表达较成年SO组明显减少(P＜0.05).结论 老年大鼠缺血性室性心律失常发生率明显增加,而迷走神经刺激的抗缺血性室性心律失常的效应明显减弱,其机制可能与老年大鼠心室肌Cx43表达较成年大鼠明显减少有关.     

迷走神经刺激对老年大鼠缺血性室性心律失常的影响

目的：探讨急性心肌缺血时迷走神经刺激对老年大鼠缺血性室性心律失常的影响及其潜在的作用机制。方法：雄性SD大鼠80只,结扎大鼠冠状动脉前降支制备急性心肌缺血模型分为：（1）成年组：心肌缺血组（MI组,陀=15）、心肌缺血＋迷走神经刺激组（MI—Vs组,乃=15）和假手术组（sO组,n=10）;（2）老年组：心肌缺血组（MI组,儿=15）、心肌缺血＋迷走神经刺激组（MI．VS组,凡=15）和假手术组（S0组,n=10）。心电图监测各组室性心律失常的发生,并进行比较。结果：结扎冠状动脉30min内,老年MI组室速和室颤发生率较成年MI组显著增加（P〈0．05）;老年MI．VS组与老年MI组室速和室颤发生率无明显变化（P〉0．05）,老年MI—VS组不可逆性室颤发生率较老年MI组明显减少（P〈0．05）。结论：老年大鼠缺血性室性心律失常发生率明显增加,而迷走神经刺激的抗缺血性室性心律失常的效应却明显减弱。     

冠心病患者血清磷脂多不饱和脂肪酸谱与炎症关系

目的探讨冠心病患者血清磷脂多不饱和脂肪酸谱与炎症关系。方法选择2016年6月至2018年6月在郑州中心医院接受治疗的100例冠心病患者(观察组)及100例同期健康体检者(对照组)进行研究。受试者均经禁食12 h后抽取空腹外周静脉血5 mL,进行炎症因子、血清饱和脂肪酸与不饱和脂肪酸检测。结果观察组超敏C反应蛋白(hs?CRP)、白细胞介素?6(IL?6)、肿瘤坏死因子α(TNF?α)水平明显高于对照组,差异有统计学意义(P0.05),血清磷脂中饱和和单不饱和脂肪酸的组成差异无统计学意义(P0.05)。与健康对照组相比,观察组患者亚油酸(LA)浓度和n?6/n?3比值高于对照组,观察组患者的EPA水平、n?3 PUFA总量和EPA/AA比值低于对照组,差异有统计学意义(P0.05)。相关性分析结果显示LA浓度,n?6/n?3比值与各炎症因子均呈显著正相关,差异有统计学意义(r0,P0.05),EPA水平、n?3 PUFA总量、EPA/AA比值与各炎症因子水平均呈显著负相关,差异有统计学意义(r0,P0.05)。结论冠心病患者LA浓度,n?6/n?3比值与各炎症因子均呈显著正相关,EPA水平、n?3PUFA总量、EPA/AA比值与各炎症因子水平均呈显著负相关。     

阻断Nav1.8通道对右侧星状神经节的影响

目的 研究利用电压门控钠离子通道1.8(Nav1.8)特异性阻断剂A-803467局部阻断Nav1.8对右侧星状神经节(RSG)的影响.方法 24只成年家犬随机分为对照组(DMSO)、低浓度组、中浓度组和高浓度组,每组6只,向RSG内局部分别注射0.1 mL DMSO和低(10 mmol/L)、中(15 mmol/L)、高浓度(20 mmol/L)的A-803467,并在注射前和注射后30 min测定由高频刺激RSG引起的最大心率的变化情况和RSG的神经活性频率和振幅变化情况.以刺激电压为横坐标,心率变化的最大百分比为纵坐标绘制出的电压-心率反应曲线以反映RSG的功能情况.结果 在基础状态时,对照组和低、中、高浓度组的RSG功能和神经活性比较,差异均无统计学意义(P>0.05);在注射A-803467后30 min,可观察到电压-心率反应曲线明显钝化,RSG功能显著降低,RSG神经活性频率和振幅明显减小,差异均有统计学意义(P<0.05).且A-803467的浓度越高,电压-心率反应曲线钝化程度越大,RSG功能降低越显著,频率和振幅越小.结论 阻断Nav1.8通道可以抑制RSG功能和神经活性,且阻断剂浓度越大,抑制效应越强.     

肠-脑轴与心血管疾病的研究进展

肠道菌群对人体代谢和肠外器官产生广泛的影响。最近研究表明,肠道菌群失调通过多种途径促进心血管疾病的发生和发展。中枢神经系统调节心血管系统,近年来研究发现由肠道菌群及其代谢产物和中枢神经系统构成的肠-脑轴在高血压、心律失常和心力衰竭等心血管疾病的发生和发展中发挥重要作用。目前,肠-脑轴与心血管疾病的详细机制日渐清晰,现就肠道菌群通过肠-脑轴促进心血管疾病的最新研究机制进行综述。     

米诺环素预处理对大鼠心肌缺血再灌注损伤和HMGB1表达的影响

目的:探讨米诺环素预处理对大鼠心肌缺血再灌注损伤的保护作用及其可能的机制。方法:成年雄性SD大鼠缺血前1h给予米诺环素(45mg/kg,ip),结扎冠脉前降支缺血30min后,恢复灌注4h;应用2,3,5-氯化三苯基四氮(TTC)法检测心肌梗死面积;试剂盒检测乳酸脱氢酶(LDH)、肌酸激酶(CK)、丙二醛(MDA)和超氧化物歧化酶(SOD);采用原位脱氧糖核苷酸末端转移酶介导的缺口末端标记(TUNEL)法检测心肌细胞的凋亡;Western blot检测高迁移率族蛋B1(HMGB1)表达。结果:与对照组相比,米诺环素预处理显著减小了心肌梗死面积,降低了心肌细胞凋亡和LDH、CK等血清心肌坏死标记物的表达(P<0.05)。米诺环素预处理也显著降低了MDA的表达,抑制了SOD的减少(P<0.05)。同时,米诺环素预处理抑制了缺血再灌注引起的HMGB1的表达(P<0.05)。结论:米诺环素预处理能够减轻心肌缺血再灌注损伤并抑制心肌细胞凋亡,这种保护作用可能与其抑制缺血再灌注诱导的HMGB1的表达有关。     

缝隙连接蛋白43在老年大鼠缺血性室性心律失常中的作用

Objective To investigate the expression of connexin43 ( Cx43 ) and effect of vagal nerve stimulation (VNS) on ventricular tachyarrhythmias during acute myocardial ischemia( MI )in aged rats. Methods Male Sprague-Dawley rats[Adult group ( ≤ 4 months) and Aged group ( ≥24 months)]:MI (n = 15 ):ligated left anterior descending coronary for 30 minutes; MI-vagal nerve stimulation(VNS) ( n = 15 ); MI-VNS-atropine (0. 5 mg/kg, n = 13 ); MI-VNS-carbenoxolone ( 10 mg/kg, n = 11 ); sham operation (SO, n = 10):without coronary ligation. Ventricular arrhythmias were monitored by an electrocardiogram. Cx43 protein expression was analyzed by Western blot. Results During the 30 minutes ligation,incidences of ventricular tachycardia (VT) and ventricular fibrillation(VF) in aged rats increased significantly compared to those of adult rats ( P ＜ 0. 05 ). VNS did not affect the occurrence of VT and VF ( both P ＞ 0.05 ); however, VNS suppressed the occurrence of irreversible VF ( P ＜ 0. 05 ); both atropine and carbenoxolone ( a gap junction inhibitor) could abolish the effect of VNS on ischemia-induced irreversible VF ( both P ＜0. 05). Ischemia did not result in changes of total Cx43 amount in adult and aged rats compared to that of SO group,respectively. The amount of nonphosphorylated Cx43 was increased markedly in adult and aged rats compared to that of SO group,respectively.Cx43 dephosphorylation induced by ischemia was significantly suppressed by VNS in adult and aged rats( P ＜0. 05 ). However,the amount of total Cx43 of SO group in aged rats was significantly decreased by 50% compared to that of SO group in adult rats ( P ＜ 0. 05 ). Conclusion The present study suggested that the incidence of ischemia-induced ventricular tachyarrhythmias increased markedly and the anti-arrhythmic effect of VNS was decreased significantly in aged rats, which may be associated with reduction of Cx43 protein of ventricle in aged rats.     

清眩补肾汤治疗原发性高血压疗效及对患者肾素-血管紧张素-醛固酮影响

目的:观察清眩补肾汤对原发性高血压患者肾素-血管紧张素-醛固酮系统的作用。方法:采用前瞻性随机临床研究方法,将150例符合标准的患者随机分为对照组75例,治疗组75例。对照组口服苯磺酸氨氯地平片,治疗组在对照组基础上加用清眩补肾汤。通过比较动态血压变化情况和血管紧张素、肾素、醛固酮指标以及用药安全性的检测进行疗效和安全性评定。结果:与对照组比较,治疗组能明显降低患者各时段血压N-SBP:(118.42±6.49)mmHg、(127.37±7.43)mmHg; D-DBP:(76.31±5.83)mmHg、(82.57±6.32)mmHg; 24-SBP:(121.23±6.31)mmHg、(129.56±7.57)mmHg;24-DBP:(73.22±5.34)mmHg、(79.46±6.54)mmHg,差异具有统计学意义(P<0.05)。同时能够降低高血压患者血管紧张素、肾素、醛固酮指标[AngⅡ(ng/L):51.93±12.39 vs. 79.33±14.26; Renin(pg/ml):5.26±1.31 vs. 7.32±1.57; ALD (ng/L):138.42±26.48 vs. 177.38±29.67,P<0.05]。比较两组患者治疗后用药安全性,肾功(UREA、Cr)、肝功(ALT、AST)情况无明显不良影响(P>0.05)。结论:清眩补肾汤可安全有效的通过抑制原发性高血压患者RAAS水平,进而降低血压水平。