去甲肾上腺素对心肌细胞凋亡、肥大的影响

目的探讨去甲肾上腺素(NE)对心肌细胞凋亡、肥大的影响.方法培养乳鼠心肌细胞暴露于三种浓度NE(2、20、200 μmol/L)36小时,检测心肌细胞凋亡率、DNA梯状带纹、心肌细胞蛋白含量、3H-亮氨酸掺入率的变化.结果高、中两种浓度NE可导致心肌细胞凋亡率明显增高和DNA梯状带纹出现,高、中、低三种浓度NE均能明显增加心肌细胞蛋白含量和3H-亮氨酸掺入率.结论 NE能诱导培养幼鼠心肌细胞凋亡和肥大.高、中、低浓度的NE,均可促进心肌细胞肥大,而较高浓度的NE方诱导心肌细胞凋亡.     

去甲肾上腺素对心肌细胞凋亡、肥大的影响

目的 探讨去甲肾上腺素(NE)对心肌细胞凋亡、肥大的影响。方法 培养乳鼠心肌细胞暴露于三种浓度NE(2、20、200μmol／L)36小时，检测心肌细胞凋亡率、DNA梯状带纹、心肌细胞蛋白含量、^3H-亮氨酸掺入率的变化。结果高、中两种浓度NE可导致心肌细胞凋亡率明显增高和DNA梯状带纹出现，高、中、低三种浓度：NE均能明显增加心肌细胞蛋白含量和^3H-亮氨酸掺人率。结论 NE能诱导培养幼鼠心肌细胞凋亡和肥大。高、中、低浓度的NE，均可促进心肌细胞肥大，而较高浓度的NE方诱导心肌细胞凋亡。     

肾上腺素、去甲肾上腺素刺激培养的大鼠心肌细胞凋亡

目的 :观察肾上腺素 （ AD）或去甲肾上腺素 （ NA）刺激体外培养的大鼠心肌细胞凋亡 ,探讨其作用机制。方法 :大鼠心肌细胞分别暴露于 10 - 7mol/L 的 NA,10 - 7m ol/L 的 AD,NA+酚妥拉明 （ 10 - 7m ol/L） ,NA+艾司洛尔 （ 10 - 7mol/L） ,AD+酚妥拉明 （ 10 - 7m ol/L）或 AD+艾司洛尔 （ 10 - 7mol/L） 2 4 h。流式细胞仪检测凋亡水平。结果 :NA使凋亡细胞百分率由 （ 4 .2± 1.6） %增加到 （ 10 .0± 5 .0 ） % （ P<0 .0 1;n=8） ,此作用可被艾司洛尔完全抑制 ,而不受酚妥拉明影响。AD与 NA的作用相仿 ,使凋亡细胞百分率增加到 （ 12 .8± 7.9） % ,且 AD诱导的凋亡同样被艾司洛尔完全抑制但不受酚妥拉明的影响。结论 :AD和 NA可能通过激活 β肾上腺素能通路 ,促进体外培养的大鼠心肌细胞凋亡     

去甲肾上腺素对心肌细胞CGRP表达变化的影响

目的观察去甲肾上腺素(NE)诱导培养心肌细胞CGRP表达的变化。方法采用1 d~3 d龄的Sprague-Dawley(SD)大鼠建立体外培养新生大鼠心肌细胞模型,选用20孔培养第4天~第5天呈亚融合状态下细胞随机分为5组,每组4孔,即对照组(C组)和NE1 h3、h、6 h、12 h组。细胞培养基内加入NE后,取样本进行测定。采用免疫细胞化学染色技术观察心肌细胞内CGRP表达的变化。结果 NE组CGRP免疫反应阳性物质在各时点均较对照组增多,并随缺血时间延长呈现不同的变化趋势:1h、3 h、6 h和CGRP免疫反应阳性物质显著增多,6 h达最高,12 h稍有下降。结论 NE在细胞水平可上调心肌细胞CGRP表达。     

去甲肾上腺素诱导心肌细胞肥大的机制

目的 :探讨去甲肾上腺素 (NE)诱导产生心肌细胞肥大的机制。方法 :采用测定心肌细胞直径及3 H 亮氨酸 (3 H leu)掺入率的方法 ,观察NE、哌唑嗪 (PRAZ)及普萘洛尔 (Pro)对SpragueWawley大鼠培养心肌细胞肥大的影响。结果 :NE可以促进心肌细胞直径增大及3 H leu掺入率的增加 (均P <0 .0 1)。PRAZ及Pro均可阻断NE的上述作用 ,以Pro的阻断作用最为显著。结论 :NE可促进心肌细胞肥大 ,而这种作用是通过PRAZ和Pro介导的 ,Pro起主要作用     

去甲肾上腺素对肝星状细胞增殖和凋亡的影响

目的探讨交感神经递质去甲肾上腺素（NE）对HSC细胞株（CSFC）增殖和凋亡的影响。方法体外培养CFSC,分为以下6组：（1）空白对照组,为单纯CFSC培养;（2）交感兴奋（NE）组;（3）交感抑制（酚妥拉明＋普萘洛尔）组;（4）α肾上腺素受体（AR）阻滞（酚妥拉明）组;（5）β1AR阻滞（CGP20712A）组;（6）β2AR阻滞（ICI118551）组。MTT法测定细胞增殖;TUNEL法观察CFSC凋亡状况;流式细胞仪检测细胞凋亡率;倒置相差显微镜观察细胞形态学变化。结果MTT法显示,NE对CFSC具有明显的促增殖作用,加入α-AR、β1AR、β2AR阻滞剂后细胞增殖均受到明显抑制。NE作用于CFSC 24h,TUNEL法显示CFSC的凋亡率显著低于对照组（6.60%±3.05%与12.60%±4.76%,P〈0.05）;加入AR阻滞剂后CFSC凋亡率升高,其中α-AR和β2AR阻滞剂作用最显著。同时,流式细胞仪显示加入NE后CFSC凋亡率也显著降低（2.29%±0.22%与3.06%±0.57%,P〈0.05）;与TUNEL结果一致。NE对细胞形态没有明显影响。结论交感神经递质NE对体外活化的CFSC具有促增殖作用,并且可以抑制CFSC的凋亡,可能主要通过α受体和β2体起作用。     

缺血再灌注时心肌细胞凋亡情况及去甲肾上腺素预处理对其影响

目的　探讨微量去甲肾上腺素预处理对大鼠缺血再灌注心肌细胞凋亡的影响。方法　大鼠在体缺血再灌注 (I/ R)模型 ,分别以缺血前去甲肾上腺素预处理 (NE- P) ,缺血预处理 (IP) ;采用末端脱氧核苷酸转换酶介导的生物素平移缺口末端标记技术 (TUNEL )检测各组心肌细胞凋亡情况及心肌梗死范围。结果　 I/ R组细胞凋亡率 (43.33%± 4.92 % )较高 ,NE- P组及 IP组虽然也有一定的心肌细胞凋亡率 :2 5.2 4 %± 1 .56% ,2 4 .44%± 2 .96% ,但较 I/ R组明显降低 (P<0 .0 0 1 )。 IP组及 NE- P组心肌梗死范围较 I/ R组明显减少 ,IP组及 NE- P组两项指标无显著差异。结论　心肌缺血再灌注损伤可诱发心肌细胞凋亡 ,NE- P能明显减少缺血再灌注诱导的心肌细胞凋亡的发生率 ,能明显减少心肌梗死范围 ,减轻缺血再灌注损伤 ;NE- P减少心肌梗死范围、减轻缺血再灌注损伤的机制可能与其能明显减少心肌细胞凋亡有关。     

双去甲氧基姜黄素对星型孢菌素诱导心肌细胞凋亡的影响

目的探讨双去甲氧基姜黄素(BDMC)对星型孢菌素(STS)诱导的原代心肌细胞凋亡的影响。方法常规培养C57BL/6J小鼠原代心肌细胞,分为4组:对照组、STS组、BDMC预处理+STS组、BDMC组。CCK-8法检测心肌细胞生存率,1unel检测心肌细胞凋亡情况,Caspase-3酶活性试剂盒检测caspase-3活性,活性氧检测试剂盒检测心肌细胞内活性氧(ROS)水平。结果终浓度为100μmol/L的BDMC预处理能显著提高心肌细胞生存率降低caspase-3酶活性,降低心肌细胞凋亡率和细胞内ROS水平(P0.05)。结论 BDMC可通过降低STS处理后的心肌细胞内ROS水平,抑制心肌细胞凋亡,达到保护损伤心肌细胞的作用。     

稳心颗粒对去甲肾上腺素诱导的心肌细胞H9C2增殖及其Cx43 mRNA表达的影响

目的观察稳心颗粒(WXKL)对去甲肾上腺素(NE)诱导的心肌细胞H9C2增殖及其缝隙连接蛋白Cx43mRNA表达的影响。方法将H9C2细胞分为四组:对照组用常规培养基培养,NE组用加入NE的常规培养基培养,WXKL组用加入WXKL的常规培养基培养,NE+WXKL组用加入含有NE和WXKL的培养基培养。培养24 h后用MTT法测定心肌细胞活力;在培养72 h后测定心肌细胞直径和细胞蛋白,提取RNA,对Cx43 mRNA进行RT-PCR扩增,琼脂糖凝胶电泳观察结果。结果与对照组相比,NE组H9C2细胞增殖率下降(P<0.05)、直径增大且蛋白含量增加(P均<0.05),其Cx43 mRNA表达减少(P<0.05);与NE组相比,NE+WXKL组H9C2细胞增殖率上升(P<0.05)、直径减小且蛋白含量下降(P均<0.05),其Cx43 mRNA表达上升(P<0.05)。结论 WXKL可改善NE诱导的H9C2细胞的肥大以及Cx43的表达下调,可能是其抗心律失常的机制之一。     

去甲肾上腺素对缺氧心肌细胞钙通道的影响

目的 :研究去甲肾上腺素 ( NE)对缺氧心肌细胞钙通道的影响。方法 :运用全细胞膜片钳记录技术检测 NE对缺氧豚鼠心肌细胞钙通道电流 ( ICa)的影响。结果 :NE( 1× 10 - 8m ol/ L)可明显增加缺氧及缺氧 /再灌注心肌细胞 ICa( P <0 .0 1,<0 .0 5 ) ,使缺氧心肌细胞 ICa电流 -电压曲线下移 ;在缺氧状态及缺氧 /再灌注状态下 ,NE对心肌细胞 ICa的作用差异无显著性意义 ( P >0 .0 5 )。结论 :NE增加心肌细胞 ICa为其致缺血及缺血 /再灌注性心律失常机制之一     

维生素E对再灌注心律失常的预防作用

60只麻醉开胸 SD大鼠 ,可逆结扎左冠状动脉主支 5 m in后解除结扎 6 0 m in,引发再灌注心律失常 (RA) ,动物分为生理盐水 (NS,10 m l/kg,ig)、维生素 (VE,5 0 0 m g/kg,ig)与超氧化物歧化酶 (SOD 5 0 0 0 U /kg,iv) 3组。用 RM-6 0 0 0多导生理记录仪监测 ECG 。结果 NS与 SOD组 RA总发生率均为 95 % ,V E组为 35 % (P<0 .0 0 1)。 N S,SO D及 VE组心室纤颤发生率与死亡率分别为 45 ,40 % ;5 0 ,2 5 % ;15 ,0 %。 V E组显著比 NS,SOD组低     

Effect of Vitamin E on Aspirin-Induced Gastric Mucosal Injury in Rats

We investigated the effect of vitamin E on aspirin-induced gastric mucosal injury in rats. Twenty-eight male Sprague-Dawley rats were divided into four groups and were fed for 20 weeks with a diet containing <0.1 mg/100 g of -tocopherol (vitamin E-deficient), 2 mg/100 g of -tocopherol (normal and vitamin E-sufficient), or 50 mg/100 g of -tocopherol (vitamin E-supplemented). In vitamin E-deficient rats, oral administration of aspirin (200 mg/kg) plus HCl created more severe hemorrhagic erosions than in other rats. Vitamin E-deficient rats had higher levels of thiobarbituric acid reactive substances, myeloperoxidase activity, and cytokine-induced neutrophil chemoattractant in the gastric mucosa. Flow cytometry showed that CD18 expression on stimulated neutrophils was higher in vitamin E-deficient rats than in vitamin E-supplemented rats. These results suggest that vitamin E protects against aspirin-induced gastric mucosal injury by inhibiting lipid peroxidation and accumulation of activated neutrophils.     

不同剂量卡维地洛对心衰大鼠心肌氧化应激和细胞凋亡的影响

目的 :探讨不同剂量卡维地洛 （CAR）对心肌梗死后大鼠心肌细胞凋亡的影响及 CAR治疗充血性心力衰竭（CHF）的作用机制。方法 :将雄性 Waistar大鼠前降支结扎 ,于术后 1周开始分别给予大剂量 CAR（HCAR组 ,6 0mg· kg- 1· d- 1 ）和小剂量 CAR（L CAR组 ,6 m g· kg- 1· d- 1 ）干预 7周 ,观察不同剂量 CAR对大鼠血流动力学参数、心肌细胞凋亡、心肌丙二醛 （MDA）含量和总抗氧化能力 （TAOC）的影响。结果 :CAR可改善心功能指标 ,降低心肌细胞凋亡指数及 MDA浓度 ,上调 TAOC水平 ,其中对心肌细胞凋亡指数 （HCAR组为 4 .6 %± 1.1% ,L CAR组为 8.0 %± 2 .0 % ）、TAOC（HCAR组为 1.92± 0 .2 0 U· mg- 1 ,L CAR组为 1.5 9± 0 .12 U· mg- 1 ）的影响以HCAR组明显。结论 :CAR可有效地减少心肌梗死后心肌细胞凋亡 ,防止 CHF的发生、发展 ,效果以大剂量明显 ,这可能与其维护心肌抗氧化防御系统有关     

Effects of ursodeoxycholic acid in combination with vitamin E on adipokines and apoptosis in patients with nonalcoholic steatohepatitis

Background/Aims: Adipokines and hepatocellular apoptosis participate in the pathogenesis of nonalcoholic steatohepatitis (NASH). In a randomized trial ursodeoxycholic acid (UDCA) with vitamin E (VitE) improved serum aminotransferases and hepatic histology. The present work evaluates the effect of this combination on adipokines and hepatocellular apoptosis. Methods: Circulating levels of adiponectin, resistin, leptin, interleukin (IL)‐6, IL‐8, retinol binding protein‐4, monocyte chemoattractant protein‐1 and tumour necrosis factor‐α were measured by enzyme‐linked immunoassays at the beginning and after 2 years of treatment with either UDCA+VitE, UDCA+placebo (P) or P+P. Apoptosis was assessed by immunohistochemistry for activated caspase‐3 and circulating levels of apoptosis‐associated cytokeratin 18 fragments (M30). Results: Levels of adiponectin increased in patients treated with UDCA+VitE, whereas they decreased in the two other groups (P<0.04) and correlated with the improvement of liver steatosis (P<0.04). M30 levels worsened in the P/P group and improved in the other two groups. They correlated with hepatocellular apoptosis (P<0.02) and steatosis (P<0.02) as well as negatively with adiponectin levels (P<0.04). Conclusions: UDCA+VitE improves not only aminotransferase levels and liver histology of patients with NASH, but also decreases hepatocellular apoptosis and restores circulating levels of adiponectin. These results suggest that the UDCA+VitE combination has metabolic effects in addition to its beneficial cytoprotective properties.     

The Effect of Vitamin E on Haemolysis in Paroxysmal Nocturnal Haemoglobinuria: In vitro and in vivo Studies

The administration of vitamin E, a natural antioxidant, to a patient with paroxysmal nocturnal haemoglobinuria (PNH) failed to diminish the urinary excretion of ⁵⁹Fe as monitored by ⁵⁹Fe whole body counting and urinary loss of isotope. However, in vitro vitamin E corrected the increased sensitivity of PNH red cells to haemolysis by hydrogen peroxide. These results support the concept that the susceptibility of PNH red cells to lipid peroxidation is an in vitro phenomenon bearing little relation to the mechanism of in vivo haemolysis.     

维生素E对醛固酮诱导的大鼠心肌重构及氧化应激的干预作用

目的:观察外源性醛固酮(aldosteronre,Ald)灌注对大鼠心肌重构和氧化应激水平的影响,以及抗氧化剂维生素E(VitE)的干预作用。方法:大鼠随机分为:①对照组,②Ald组,③Ald+VitE组和④Ald+螺内酯(spironolactone,Spi)组。用黄嘌呤氧化法测定超氧化物歧化酶的活性,用巴比妥酸比色法测定丙二醛的含量,Masson三色法检测心肌胶原,细胞凋亡原位检测法检测心肌细胞凋亡。结果:与Ald组比较,Ald+VitE组心肌胶原、凋亡指数、丙二醛明显减少,超氧化物歧化酶明显增加(P<0.05)。Ald+VitE组与Ald+Spi组上述指标差异无统计学意义。结论:VitE能够降低Ald诱导的大鼠心肌氧化应激水平,显著改善心肌纤维化和心肌细胞凋亡。     

Antioxidant Effects of Lovastatin and Vitamin E on Experimental Atherosclerosis in Rabbits

The effects of the administration of vitamin E (10 mg/day) plus lovastatin (2 mg/day; group A, n = 10), lovastatin alone (2 mg/day; group B, n = 10), and placebo (group C, n = 10) were compared over 24 weeks in a randomized, single-blind controlled trial. All groups of rabbits received a trans fatty acid (TFA)–rich diet (5–10 g/day) for 36 weeks. Treatment with vitamin E plus lovastatin (group A) and lovastatin (group B) started after 12 week of administration of TFA-rich diet was associated with a significant but similar decline in serum cholesterol, low-density lipoprotein (LDL) cholesterol, and triglycerides in both groups at 36 weeks. Lipid peroxides and diene conjugates showed a significant decline in association with a significant increase in the plasma level of vitamin E in group A rabbits at 36 weeks. However, the lovastatin group B showed a lesser but significant decrease in lipid peroxides and diene conjugates at 36 weeks, indicating that lovastatin may have antioxidant activity. In control group C, the increase in blood lipids and oxidative stress at 36 weeks was much greater than the decrease in groups A and B. After experimental lipid peroxidation at 24 weeks in all of the rabbits, 2 of 10 group B and 3 of 10 group C rabbits died due to coronary thrombosis; there were no deaths in group A. Thus antioxidant therapy with vitamin E can provide protection against death due to free radical stress. Aortic lipids and sudanophilia indicating athorosclorosis were significantly lower in groups A and B than in group C. The atherosclerotic coronary plaque sizes were significantly smaller in group A (18.5 ± 3.6 μm) than in groups B (41.6 ± 4.2 μm) and C (85 ± 6.7 μm). Aortic plaque sizes were also smaller in group A than in group B and C. It is possible that antioxidant therapy with vitamin E, as an adjunct to lipid lowering with lovastatin, can provide additional benefit in the inhibition of oxidative stress and atherosclerosis. The antioxidant activity of lovastatin has not been reported, to our knowledge. This revised version was published online in July 2006 with corrections to the Cover Date.     

Vitamin E attenuates myocardial ischemia-reperfusion injury in murine AIDS

The incidence of myocardial infarction in patients who have the aquired immunodeficiency syndrome (AIDS) is increasing. However, no effective therapeutic agents have been discovered to reduce myocardial ischemia-reperfusion (I/R) injury in pathologies associated with AIDS. The aim of this study was to determine if infarct size is increased in murine AIDS after I/R injury and if I/R injury could be attenuated with vitamin E supplementation. Three groups of mice were studied: control, murine AIDS, and murine AIDS with vitamin E supplementation. Anesthetized mice were subjected to 30 min of left anterior descending coronary artery occlusion and 120 min of reperfusion. The hearts in mice that had murine AIDS had a larger infarct size compared to controls after I/R injury. Vitamin E supplementation significantly reduced infarct size and inhibited polymorphonuclear neutrophil (PMN) CD11b expression (p<0.05). However, vitamin E supplementation did not affect PMN reactive oxygen species (ROS) production and platelet CD62p expression. These results suggest that the reduction of myocardial I/R injury with vitamin E supplementation may be the result of the inhibition of PMN CD11b expression. Vitamin E may be a promising prophylactic agent for the reduction of the severity of myocardial I/R injury in patients who have AIDS.     

Vitamin E consumption by human blood platelets activated by latex particles

Human blood platelet activation elicited by latex particles is associated to a 30% decrease in the cellular content of vitamin E. The vitamin E consumption is inhibited by the addition of catalase (500 U/ml) and azide (1 mM), but it is not affected by potassium cyanide (1 mM). It may be proposed that the challenge of platelets with particulate stimuli causes generation of oxygen reduction products, which leads to vitamin E depletion.