美托洛尔对缺氧-再给氧心肌细胞C-FOS表达和游离钙的影响

目的和方法研究表明,c-fos是细胞核内重要的原癌基因,它的表达产物对细胞具有重要意义,c-fos的表达产物Fos单独不能与DNA结合,Fos和Jun通过亮氨酸拉链形成二聚体,即具有活性的转录因子复合物AP.1,AP.1通过顺式作用激活相关的基因,从而调节基因的表达与蛋白质的合成。在正常情况下,c-fos在细胞中仅有低水平表达,但在心肌缺血再灌注中c-fos表达迅速增加。心肌细胞在缺氧-再给氧（A/R）时会产生大量氧自由基,氧自由基可诱导原癌基因表达,原癌基因表达程度与心肌细胞复氧损伤程度及细胞内游离钙有关。Ca²⁺超载可导致细胞不可逆损伤及细胞信息传递的紊乱,大量氧自由基生成及脂质过氧化物增强是心肌缺血再灌注损伤的主要机制之一。超氧化物岐化酶（SOD）作为重要的抗氧化酶可清除超氧阴离子自由基,保护心肌细胞,减轻心脏功能的损伤程度,其活性高低反映了机体清除氧自由基的能力。本研究通过培养心肌细胞,在细胞水平模拟心肌A/R损伤,用粘附式细胞仪,以荧光探针技术激光共聚焦扫描及免疫组化、灰度分析观察美托洛尔对培养心肌细胞A/R时细胞内钙(Ca²⁺)荧光强度、SOD活性及c-Fos表达的影响。结果心肌细胞A/R后,细胞内Ca²⁺荧光强度升高,对照组为:167.3±32.8,0.3±0.04,A/R组为:562±128.6,97.6±12.8,P<0.01。细胞培养液中SOD活性、平均灰度值降低,P<0.01。美托洛尔组上述改变得到明显改善,细胞内钙(Ca²⁺)荧光强度显著降低为376±39.1,22.8±8.2,细胞培养液中SOD活性、平均灰度值显著增高,P<0.05。^#P<0.01与对照组比较*P<0.05与A/R组比较。结论本实验证实美托洛尔能可明显减少c-fos的表达,提高心肌细胞SOD活性,有效清除超氧阴离子自由基,保护细胞膜结构完整性及阻止Ca²⁺内流,减轻Ca²⁺超载,对A/R心肌具?

Two monitoring methods of oral anticoagulation in patients with mechanical heart valve prostheses:a Meta-analysis

Background Oral anticoagulation with warfarin has become the standard antithrombotic therapy for the patients with mechanical heart valve prothesis.The monitoring method of self-monitoring or self-management is promising to optimize the use of warfarin,but most of the previous studies have included patients with various indications of oral anticoagulant therapy other than valve procedure.This study is intended to evaluate the effects of new monitoring method compared with traditional monitoring in patients with mechanical heart valve prostheses.Methods Relevant literature finished before Dec.2010 were searched through a number of digital database.And then they are pooled by RevMan 4.2 in three fields:rate within the target range,test frequency and occurrence rate of poor events.Results Five randomised control trials with a total of 1662 patients were identified.Pooled estimates showed significant reductions in thromboembolic events(odds ratio 0.55,95%CI 0.35～0.85) and major haemorrhage(0.80,0.54～1.18).Trials of combined self-monitoring and self-adjusted therapy showed significant reductions in thromboembolic events(0.56,0.32～0.98),but not major haemorrhage(1.05,0.60～1.83).No difference was noted in minor haemorrhage and all-cause mortality.All trials reported improvements in the mean proportion of international normalisation ratios in range.Conclusions Self-monitoring can improve the quality of oral anticoagulation therapy in the patients with mechanical.Patients capable of self-monitoring and self-adjusting therapy have fewer thromboembolic events than those who self-monitor alone.However,self-monitoring is not feasible for all patients,and requires identification and education of suitable candidates heart valve prostheses.