神经调节蛋白-1对心肌梗死大鼠葡萄糖代谢的改善作用

目的:探讨神经调节蛋白-1（NRG-1）对SD大鼠心肌梗死后心脏葡萄糖代谢的改善作用。方法:成年雄性SD大鼠随机分为3组：假手术组、心肌梗死组和心肌梗死+NRG-1组,每组6只。通过结扎冠状动脉左前降支建立心肌梗死模型,心肌梗死+NRG-1组大鼠在建模成功后,于尾静脉注射NRG-1β（100 μg/kg）,每周2次,共...     

神经调节蛋白-1干预对大鼠心肌梗死后低电压区起搏阈值的影响

目的：探讨神经调节蛋白一1（NRG-1）干预对大鼠心肌梗死后低电压区起搏阈值的影响。方法：采用冠状动脉前降支结扎法建立心肌梗死大鼠模型,34只心肌梗死大鼠被随机均分为两组：NRG-1干预组（接受NRG-1腹腔注射）和对照组（接受同体积生理盐水腹腔注射）。2周后测试大鼠心肌梗死后梗死相关的低电压区的起搏阈值,并检测低电压区Cx43（连接蛋白家族的一种蛋白质）的表达。结果：药物干预2周时,NRG-1组起搏阈值明显低于对照组起搏阈值[（O．7167±0．194）V比（1．466±0．503）V,P=0．002];心肌梗死后低电压区NRG-1组Cx43表达较对照组明显增多[（O．95±0．20）比（0．30±0．15）,P〈0．001]。结论：NRG-1明显降低大鼠心肌梗死后低电压区起搏阈值,其机制可能与增加Cx43表达,改善心肌细胞间电传导有关。     

神经调节蛋白-1在脑缺血中的保护作用

神经调节蛋白-1是表皮生长因子家族成员,对神经元的存活、发育、迁移、髓鞘形成、突触可塑性以及功能均有重要作用.文章主要概述神经调节蛋白-l的结构、功能及其在脑缺血过程中的神经保护作用,其机制可能包括抑制早期炎症反应和凋亡,调节神经营养因子表达.     

神经调节蛋白-1在脑缺血中的保护作用

神经调节蛋白-1是表皮生长因子家族成员,对神经元的存活、发育、迁移、髓鞘形成、突触可塑性以及功能均有重要作用.文章主要概述神经调节蛋白-l的结构、功能及其在脑缺血过程中的神经保护作用,其机制可能包括抑制早期炎症反应和凋亡,调节神经营养因子表达.     

神经调节蛋白-1在脑缺血中的保护作用

神经调节蛋白-1是表皮生长因子家族成员,对神经元的存活、发育、迁移、髓鞘形成、突触可塑性以及功能均有重要作用.文章主要概述神经调节蛋白-l的结构、功能及其在脑缺血过程中的神经保护作用,其机制可能包括抑制早期炎症反应和凋亡,调节神经营养因子表达.     

神经调节蛋白-1对大鼠心肌缺血/再灌注损伤保护作用的研究

目的:探讨神经调节蛋白-1(NRG-1)对大鼠心肌缺血/再灌注(I/R)损伤的保护作用及其潜在机制。方法:雄性,SD大鼠,分三组:假手术组(n=8)、心肌(I/R)组(n=8)和NRG-1+I/R组(n=9)。通过结扎冠状动脉左前降支45 min,再灌注3 h建立在体大鼠心肌I/R模型。用伊文氏蓝/2,3,5-三苯基氯化四氮唑(TTC)染色法测定心肌梗死范围。用脱氧核糖核苷酸末端转移酶介导的d UTP缺口末端标记法(TUNEL)染色法检测心肌细胞凋亡指数;免疫荧光法测定线粒体膜电位水平;用Western blot方法检测线粒体细胞色素c的转位、凋亡相关因子Bcl-2和Bax的表达;caspase 3试剂盒检测caspase 3活性;用透射电镜观察心肌组织线粒体超微结构。结果:与假手术组相比,I/R组心肌细胞凋亡显著增加[(23.2±3.8)vs.(3.0±1.3)%,P0.01],心肌线粒体膜电位降低[(209.1±13.6)vs.(336.8±10.3)m V,P0.05],细胞色素c向胞浆发生转位,caspase 3活性显著升高[(20.1±3.6)vs.(8,3±1.5),P0.01]。与单纯I/R组比较,NRG-1给药显著降低I/R大鼠心肌的梗死面积/危险区面积[(28.6±9.2)vs.(51.7±7.8)%,P0.01],减少心肌细胞凋亡指数[(11.9±3.5)vs.(23.2±3.8)%,P0.01],升高Bcl-2/Bax蛋白表达比值[(1.647±0.172)vs.(0.490±0.080),P0.01],升高线粒体膜电位[(327.2±15.4)vs.(209.1±13.6)m V,P0.05],抑制细胞色素c向胞浆的转位[(0.207±0.055)vs.(0.483±0.075),P0.01],降低心肌caspase 3活性[(9.3±2.6)vs.(20.1±3.6),P0.01],改善线粒体超微结构。结论:NRG-1具有抗心肌I/R损伤的保护作用,其机制部分通过抑制线粒体介导的心肌细胞凋亡途径实现。     

植入式心电事件监测仪在心肌梗死大鼠室性心律失常监测中的应用

目的探讨清醒状态下应用废旧的植入式心电事件监测器(Reveal LINQ~(TM))监测大鼠心肌梗死(简称心梗)诱导的室性心律失常的可行性。方法 10只SD大鼠麻醉状态下开胸并结扎冠状动脉左前降支建立心梗模型,经胸骨左缘4～5肋间皮下隧道植入废旧的Reveal LINQ~(TM),选用自动激活模式连续记录全天时段动态心电活动4周,根据事件触发个数手动统计3类室性心律失常总数及发生率。结果心梗术后存活的8只SD大鼠均成功接受Reveal LINQ~(TM)植入,植入相关并发症发生率为0。8只SD大鼠第1周、2周、3周、4周单个室性早搏(简称室早)总数:17、72、28和14次;成对室早总数:1、14、5和1阵;室早三连总数:2、4、2和1阵;4周内室性心律失常发生率:37.5%、87.5%、50%和25%。结论废旧的Reveal LINQ~(TM)可安全、稳定、有效地监测SD大鼠心梗后室性心律失常的发生。     

急性心肌梗死后心脏结构和神经重构的实验研究

目的探讨家猪急性心肌梗死(简称心梗)后心脏结构和神经重构的相关分子机制。方法 16只家猪在禁食12h,禁饮4h后随机分为假手术组(n=6)和心梗组(n=10)。应用置入经皮冠状动脉腔内球囊堵闭前降支的方法制备家猪心梗模型(假手术组放置球囊,但不堵闭);利用超声心动图观察心梗后心脏结构特性,三维标测系统检测左室电压改变。同时应用免疫组化、Western blot和ELISA实验方法分析心肌结构及神经重构相关因子的含量变化。结果心梗组4只家猪因心室颤动死亡。与假手术组比较,心梗组舒张期室间隔厚度和左室舒张期后壁厚度均变薄(P<0.05),而左室舒张末期内经变大(P<0.05);左室短轴缩短率和左室射血分数变小(P<0.05)。与假手术组比较,心梗组神经生长因子相关蛋白-43、酪氨酸羟化酶标记的阳性神经密度明显增加(P<0.05),神经抑制因子Sema3a表达明显下降(P<0.05);心梗组白介素-1β、肿瘤坏死因子-α、内皮素-1、神经生长因子、促血管生成素-2表达明显上调(P<0.05)。结论急性心梗后心脏结构和神经重构发生重大改变,此将影响心肌的功能特性。     

NMDA受体在心肌梗死后抑郁大鼠心电生理异常中的作用

目的 通过建立心肌梗死(MI)后抑郁大鼠模型,检测心室颤动(室颤)阈值及心肌细胞N-甲基-D-门冬氨酸(N Methyl D Aspartate,NMDA)受体亚基(NMDAR1)、Kv4.2的表达情况,探讨NMDA受体在心肌梗死后抑郁大鼠心电生理异常中的作用.方法 将50只SD大鼠随机均分为对照组、抑郁组(MDD组)、心肌梗死组(MI组)、MI后抑郁组(MI+MDD组)和氟西汀组(F组).通过结扎冠状动脉和慢性不可预见性温和应激,建立MI和抑郁大鼠模型,并运用心电图、Masson染色、糖水偏好实验和旷场实验对模型进行鉴定.采用S1S1程序电刺激左心室,测量各组大鼠室颤阈值.通过免疫组化法半定量各组大鼠心肌细胞NMDAR1、Kv4.2的表达.结果 ①心电图、Masson染色、糖水偏好实验和旷场实验结果显示模型制作成功;②与对照组[(8.3±0.7)V]相比,MI组、MDD组、MI+MDD组室颤阈值降低,F组室颤阈值升高[(5.2±0.9)V、(7.4±0.6)V、(4.0±0.5)V、(12.0±0.3)v],差异有统计学意义(P＜0.05),其中MI+MDD组最低;③免疫组化结果:MDD组和MI+MDD组大鼠心肌细胞内NMDAR1呈强阳性表达,显著高于其他3组,F组表达量最低;各组大鼠心肌细胞中均可见Kv4.2阳性表达,对照组的表达量最高,MI+MDD组的表达量最低,F组较MI+MDD组表达增加.结论 心肌细胞NMDA受体过度表达和Kv4.2表达下降可能是MI后抑郁大鼠心电生理异常的分子机制之一.     

血管紧张素Ⅱ对心肌微血管内皮细胞神经调节蛋白-1表达的影响

目的观察血管紧张素Ⅱ(AngⅡ)对心肌微血管内皮细胞(CMEC)表达神经调节蛋白-1(NRG-1)的影响。方法取SD乳鼠心脏组织用含生长因子的培养液诱导培养CMEC,选生长良好的第2代CMEC分为三组:空白对照组单纯培养不干预,AngⅡ组加入AngⅡ100 nmol/L,缬沙坦组加入AngⅡ100 nmol/L及缬沙坦10μmol/L联合干预。培养24 h后分别收集CMEC。RT-PCR法检测NRG-1 mRNA表达变化;Western blot检测NRG-1蛋白表达。结果与空白对照组比较,AngⅡ组NRG-1 mRNA和蛋白表达明显下降(P均<0.05);缬沙坦组NRG-1 mRNA和NRG-1蛋白表达明显高于AngⅡ组(P均<0.05),与对照组比较无显著性意义(P>0.05)。结论 AngⅡ可抑制CMEC表达NRG-1基因,而缬沙坦可拮抗此作用。     

抑郁对大鼠心室肌电生理学特性的影响

目的探讨抑郁对大鼠心室肌电生理学特性的影响。方法将SD大鼠随机分为健康对照组、抑郁组、糖尿病组及抑郁合并糖尿病组各10只。抑郁动物模型通过持续4周的慢性温和应激获得,糖尿病动物模型通过皮下注射四氧嘧啶获得。从第5周开始对各组大鼠进行电生理学检查。测定右室心尖部、左室流出道及左室心尖部三个部位的90%单相动作电位时程(MAPD90)和心室有效不应期(VERP),并记录心室后除极的发生次数,最后通过程序刺激诱发室性心动过速或心室颤动(简称室颤),记录诱发率。结果抑郁组和糖尿病组大鼠心室MAPD90及VERP较健康对照组明显延长,而抑郁合并糖尿病组大鼠心室MAPD90及VERP较抑郁组和糖尿病组进一步延长。抑郁组和糖尿病组后除极发生次数及室颤诱发率较健康对照组增加,抑郁合并糖尿病组后除极发生次数及室颤诱发率较抑郁组和糖尿病组进一步增加。结论抑郁可引起大鼠心室肌电生理学特性的改变;抑郁及糖尿病对大鼠心室肌电生理学特性的影响可能存在累积或协同作用。     

硝酸异山梨酯对大鼠缺血心肌血管新生的影响

目的观察硝酸异山梨酯对急性心肌梗死(AMI)大鼠缺血心肌组织形态、梗死面积及毛细血管新生的影响。方法Wistar大鼠90只建立AMI模型后,随机分为5组,分别为正常组,假手术组,模型组,硝酸异山梨酯低剂量组(IDL组)和硝酸异山梨酯高剂量组(IDH组),每组18只。大鼠饲养7、14天后各随机处死9只,截取心肌组织,进行光镜、电镜观察,利用NBT染色法测定心肌梗死面积,应用免疫组织化学法测定Ⅷ因子,进而计算缺血心肌微血管密度(MVD),通过RT-PCR技术检测血管内皮生长因子(VEGF)及碱性成纤维细胞生长因子(bFGF)基因表达情况。结果光镜下观察,缺血区可见炎细胞浸润、心肌肿胀、梗死区纤维化。与模型组比较,IDL组和IDH组7、14天心肌梗死面积明显缩小,MVD明显增加(P<0.05);正常组、假手术组VEGF mRNA、bFGF mRNA表达有所减少,而IDH组则有所增加。结论硝酸异山梨酯可明显缩小AMI大鼠梗死面积,促进缺血心肌的毛细血管新生,对心肌缺血损伤具有保护作用。     

Sequence of electrophysiological property and metabolic disorder in ischemic myocardium

The relationships of electrical changes to the time course of reduction in adenosine triphosphate (ATP) content were examined in 41 dogs with coronary artery ligation and 14 control dogs. Twenty dogs with malignant ventricular arrhythmias within 10 min of ischemia (VA dogs) were characterized by widening of the composite electrogram duration (147 +/- 47 msec at 5 min). In contrast, the composite electrogram duration was narrower (71 +/- 12 msec at 5 min, p less than 0.001) in 21 dogs without malignant arrhythmias (non-VA dogs). The degree of ATP reduction in VA dogs was significantly less at 3 min (3.11 +/- 0.28 mumol X g-1, p less than 0.05) and at 5 min (2.93 +/- 0.28 mumol X g-1, p less than 0.05) than in non-VA dogs (2.76 +/- 0.22 mumol X g-1, 2.39 +/- 0.44 mumol X g-1, respectively). The width of the electrograms in VA dogs decreased gradually after 10 min of ischemia, and it was not significantly different from non-VA dogs by 13 min, which coincided with disappearance of a difference in ATP content (2.10 +/- 0.34 mumol X g-1 and 2.35 +/- 0.23 mumol X g-1 in VA dogs and non-VA dogs biopsied at 10-20 min of ischemia). It was concluded that the metabolic deterioration in VA dogs advanced more slowly than that in non-VA dogs within 5 min of ischemia and the decrease in the width of the electrogram after 10 min did not result from a partial recovery of ischemia.     

曲美他嗪对心肌缺血时细胞骨架损伤的作用

目的　探讨心肌缺血时细胞骨架改变并观察曲美他嗪对心肌缺血时细胞骨架损伤的影响 ,为临床应用提供理论依据。方法　将大白鼠随机分为对照组和用药组并制成缺血模型 ,分别于缺血 30 m in、6 0 min、12 0 min时取心肌组织用免疫组化的方法观察肌动蛋白、波形蛋白、肌球蛋白、结蛋白等心肌细胞骨架蛋白的改变 ,并用计算机图象模拟分析系统计算骨架蛋白量的变化。结果　心肌缺血 30 min即有肌动蛋白、肌球蛋白损伤 ,12 0 min时有结蛋白损伤 (P<0 .0 5 )。曲美他嗪干预后 ,心肌缺血 6 0 min、12 0 min时肌动蛋白、肌球蛋白损伤明显减少 (P<0 .0 5 )。结论　心肌缺血时可以导致细胞骨架损伤 ,曲美他嗪对心肌缺血时细胞骨架损伤有保护作用     

Effects of L-carnitine on phospholipids in the ischemic myocardium

To evaluate the protective effects of L-carnitine on the ischemic myocardium, the effects of its administration on tissue levels of high energy phosphate and phospholipids were studied in ischemic dog hearts. Myocardial ischemia was induced by the ligation of the left anterior descending coronary artery for 40 min. In the experiment, L-carnitine (300 mg/kg) was administered intravenously prior to coronary artery ligation. Mitochondrial phospholipids were extracted from nonischemic and ischemic regions of the myocardium and subsequently analyzed. In ischemic myocardial tissues, levels of adenosine 5'-triphosphate (ATP) were reduced. The decrease was significantly elevated by L-carnitine pretreatment. The mitochondrial fractions obtained from ischemic myocardia had significantly lower levels of phospholipids than those obtained from nonischemic tissues. Moreover, the amounts of phosphatidylcholine, phosphatidylinositol and phosphatidylethanolamine were significantly decreased in ischemic myocardial tissues. L-carnitine-pretreatment prevented the reduction of these phospholipids. Lysophosphatidylethanolamine and sphingomyelin did not show statistically significant decreases. This may explain why the administration of carnitine has beneficial effects on ischemic myocardium.     

Non-uniform electrophysiological properties and electrotonic interaction in hypertrophied rat myocardium

We studied the distribution and nature of the electrical changes associated with myocardial hypertrophy induced by renal hypertension in rats. Standard microelectrode techniques were used to study transmembrane action potentials recorded from endocardial, papillary muscle, and epicardial stimulation from hypertrophied (HBP) and normal (SHAM) hearts. We also determined the effects of stimulation frequency on the action potentials recorded from these preparations. To assess whether altered intercellular electrical connections contribute to the electrophysiological changes associated with hypertrophy, we analyzed the spatial steady state voltage decrement produced by passing intracellular constant current pulses and determined the effective input resistance (Rin) of endocardial HBP and SHAM preparations. Our results show that the action potential prolongation that accompanies hypertrophy is not uniform. Thus, the entire course of repolarization is prolonged in epicardial and papillary muscle fibers, but only the latter half of repolarization is prolonged in epicardial fibers. Endocardial action potentials is general, and HBP action potentials in particular, have a distinctive steep relation between duration and stimulation frequency which may be due to a difference in the rate dependence of a membrane conductance(s), although relatively greater accumulation of extracellular potassium or altered activity of the Na+-K+ pump cannot be excluded as contributing factors. In addition, the similarity in the profile of spatial voltage decrement and the values for Rin in HBP and SHAM preparations indicates that alterations in electrotonic coupling between cells are unlikely to account for the prolonged action potentials of hypertrophied myocardium.     

Effects of ischemic preconditioning on cyclinD1 expression during early ischemic reperfusion in rats

AIM: To observe the effect of ischemic preconditioning on cyclinD1 expression in rat liver cells during early ischemic reperfusion. METHODS: Fifty-four SD rats were randomly divided into ischemic preconditioning group (IP), ischemia/ reperfusion group (IR) and sham operation group (SO). The IP and IR groups were further divided into four sub-groups (n - 6). Sham operation group (SO) served as the control group (n = 6). A model of partial liver ischemia/reperfusion was used, in which rats were subjected to liver ischemia for 60 min prior to reperfusion. The animals in the IP group underwent ischemic preconditioning twice for 5 min each time prior to the ischemia/reperfusion challenge. After 0, 1, 2, and 4 h of reperfusion, serum and liver tissue in each group were collected to detect the level of serum ALT, liver histopathology and expression of cyclinDi mRNA and protein. Flow cytometry was used to detect cell cycle as the quantity indicator of cell regeneration. RESULTS: Compared with IR group, IP group showed a significantly lower ALT level in 1 h to 4 h sub-groups (P < 0.05). Proliferation index(PI) indicated by the S-phase and G2/M-phase ratio [(S G2/M)/(G0/G1 S G2/M)] was significantly increased in IP group at 0 and 1 h (26.44±7.60% vs 18.56±6.40%,41.87±7.27% vs 20.25±6.70%, P < 0.05). Meanwhile, cyclinDi protein expression could be detected in IP group. But in IR group, cyclinDi protein expression occurred 2 h after reperfusion. The expression of cyclinDi mRNA increased significantly in IP group at 0 and 1 h (0.568±0.112 vs 0.274±0.069, 0.762±0.164 vs 0.348±0.093, P < 0.05). CONCLUSION: Ischemic preconditioning can protect liver cells against ischemia/reperfusion injury, which may be related to cell proliferation and expression of cyclinD1 during early ischemic reperfusion.     

环氧化酶抑制剂干预心肌缺血损伤的实验研究

目的 :评价环氧化酶抑制剂对心肌缺血损伤 （AIM）的保护作用。方法 :将成年家兔 （1.8～ 2 .5 kg） 2 4只随机分为正常对照组 （A组 ） ,单纯心肌缺血组 （B组 ） ,心肌缺血加迪克乐克组 （C组 ） ,建立 AIM模型 ,给予相应的干预 ,术后 6 h观察血液学指标 ,缺血心肌的 HE染色及 COX- 2的多克隆抗体免疫组织化学染色进行病理观察。结果 :缺血心肌中 COX- 2高度表达 ,血液学指标示术后 6 h白细胞计数在 B、C组间有明显差异 （P<0 .0 5 ） ,i NOS测定值在A、B组有显著差异 （P<0 .0 5 ） ,MDA、SOD含量在 A、B组间有显著性差异 （P<0 .0 5 ） ,C组应用非选择性环氧化酶抑制剂 ,在术后 6 h白细胞计数升高程度与 A、B组均有显著性差异 （P<0 .0 5 ） ,i NOS测定值与 B组无显著差异（P>0 .0 5 ） ,MDA、SOD含量与 B组差异显著 （P<0 .0 5 ）。结论 :缺血心肌存在显著的炎症活动 ,环氧化酶抑制剂对实验性心肌缺血损伤有保护作用。     

Effects induced on blood platelets in ischemic and nonischemic myocardium

The function of blood platelets sampled from the coronary sinus and the superior vena cava was studied in 50 men with coronary artery disease at rest and during pacing-induced angina. At rest, a lower platelet aggregation and retention response was found in coronary sinus compared with vena caval blood. This may be due to refractoriness after previous platelet stimulation or to release of platelet inhibitors in the coronary circulation. During pacing-induced angina, lactate levels indicated that blood was sampled from ischemic myocardium in only 27 of the patients. Pacing-induced angina influenced platelet function differently in blood from ischemic and nonischemic regions. Adenosine diphosphate- and collagen-induced aggregation, platelet retention and plasma beta-thromboglobulin levels remained unchanged in blood from ischemic myocardium during pacing, but increased in blood from nonischemic regions. Thus, factors other than ischemia activated platelets in the coronary circulation during tachycardia-induced stress.     

Effects of premature depolarization on refractoriness of ischemic canine myocardium

In 25 pentobarbital anesthetized dogs we measured refractory periods (RPs) of regularly driven complexes and premature ventricular depolarizations (PVDs) with a range of coupling intervals or of regularly driven complexes and the complex following the PVD, i.e. the postextrasystolic depolarization (PED). Measurements were made during control periods and during occlusion of a branch of the left anterior descending coronary artery. The difference in control and occlusion RPs was less following some PVDs with short coupling intervals than following other PVDs with longer coupling intervals. Variations in the coupling interval of PVDs had less effect on RPs of the PVDs in ischemic than in nonischemic tissue. RPs of PEDs were prolonged with respect to RPs of regularly driven complexes in both ischemic and nonischemic tissue, but the prolongation in ischemic tissue was significantly greater than that in nonischemic tissue, 8 ± 4 msec and 2 ± 2 msec respectively, p <.001. The difference in effect of PVDs on RPs of ischemic and nonischemic tissue results in greater disparity of refractoriness between ischemic and nonischemic tissue following some long coupling interval PVDs than following some PVDs with shorter coupling intervals. In addition the greater prolongation of RPs of PEDs in ischemic than in nonischemic tissue can result in increased disparity in RPs than the disparity between ischemic and nonischemic tissue present during regular drive.