扩张型心肌病与血管紧张素转换酶基因、chymase基因多态性的研究

目的 :探讨血管紧张素转换酶 (ACE)基因插入 /缺失 (I/D)多态性及chymase(CMA)基因B种A/G多态性是否是扩张型心肌病 (DCM )的易感性标志。 方法 :采用聚合酶链反应 (PCR)和限制性片段长度多态性方法 (RFLP)检测 4 3例DCM患者和 6 3例健康者中ACE基因I/D多态性和CMA/B基因A/G多态性的频率分布 ,同时超声心动图测量左心室内径 (LVDd、LVDs)大小 ,计算射血分数 (EF)值 ,测量心胸比、血压和心率等临床指标。结果 :①ACE基因II、ID、DD基因型及I、D等位基因频率在DCM组与对照组的分布差异无显著性意义。②CMA基因AA、AG、GG基因型及A、G等位基因频率在DCM组与对照组的分布差异无显著性意义。③ACE、CMA基因型间年龄、患病史、NYHA心功能分级、LVDd、LVDs、EF值、心胸比、心率、收缩压、舒张压差异无显著性意义。④ACE、CMA基因型与LVDd、LVDs、EF值不相关。结论 :ACE基因I/D多态性及CMA/B基因A/G多态性与DCM患者心脏大小及收缩功能不相关。     

体外诱导大鼠骨髓间充质干细胞向心肌细胞定向分化的研究

Objective To investigate the role of cardiac myocytes in the differentiation of bone marrow mesenchymal stem cells (MSCs) to cardiac myocytes and the biological properties in the course. Methods The bone marrow of the extremities of the rats was flushed, and bone marrow MSCs were obtained by method of density gradient centrifugation. They were cultured. The second passage of cultured MSCs were labelled with bromodeoxyuridine (BrdU). The cardiac myocytes were obtained from the apex of rat heart with trypsin digestion method, and they were cocultured with labeled MSCs. The developmental changes of bone marrow MSCs were observed under light microscope with immunohistochemical staining for BrdU and a-sarcomeric actin on the 3rd day, anti electron microscopic examination on the 5th day. Results MSCs proliferated fast in primary culture and subculture, positive rate was (90. 34± 2. 31)%, and there was statistical difference when it compared with control group [(4.07±1.35)%, P<0. 01]. The morphology of MSCs changed significantly after coculture. There were new cells nuclei of which were positively stained for BrdU and its cytoplasm positive for actin. Under transmissive electron microscope, sarcomeres like structure and abnormal Z line were observed in cytoplasm. Conclusion Cardiac myocytes can effectively induce bone marrow MSCs to differentiate into cardiac myocytes by coculturing.     

原发性高血压患者空腹血清游离脂肪酸组成的变化

目的观察原发性高血压患者空腹血游离脂肪酸(freefattyacid,FFA)组成改变。方法采用社区人群整群抽样、病例对照方法,筛选出高血压患者109例,其中肥胖患者70例,非肥胖患者39例,并以饮食习惯相近的123例血压正常个体(其中肥胖个体66例,非肥胖者57人)为对照,用高效液相色谱直接衍生化法检测空腹血清各种FFA浓度,放免法测定胰岛素水平。结果(1)与血压正常个体比较,原发性高血压患者血清游离多不饱和脂肪酸(PUFA)水平降低(P=0.004),饱和脂肪酸(SFA)水平有增高趋势(P=0.06),P/S比值降低(P=0.000);血清PUFA中,n3PUFA水平降低[(高血压组95.8±39.6vs正常组122.0±33.4)μmol/L,P=0.000],n6PUFA水平有降低趋势(P=0.124);前者主要是DHA水平(22:6n3)降低所致[分别为(高血压组64.7±39.2vs正常组94.2±31.3)μmol/L,P=0.000],EPA(20:5n3)水平无明显变化,而α亚麻酸水平(18:3n3)则升高(分别为高血压组21.2±7.2vs正常组17.5±7.6)μmol/L,P=0.000],后者的亚油酸(18:2n6)水平有降低趋势(P=0.052)而AA(20:4n6)水平无明显变化。(2)与非高血压者相比较,原发性高血压患者C22:6/C20:5比值(n3Δ6去饱和酶活性指数)降低(P=0.002),C20:5/C18:3比值(n3Δ5、Δ6去饱和酶活性指数)有降低趋势(P=0.065)。(3)回归分析显示空腹血n3PUFA水平与舒张压水平独立负相关。结论原发性高血压患者存在空腹血游离脂肪酸组成改变,表现为PUFA(主要是n3类)水平降低和P/S比值降低;这种改变提示α亚麻酸向DHA的(22:6n3)生物转化缺陷与n3Δ6去饱和酶活性降低有关;这种改变与舒张压水平的升高独立相关。     

比索洛尔对心衰大鼠心室肌细胞瞬时外向钾电流的影响

目的观察比索洛尔对容量超负荷心衰大鼠左室心肌细胞瞬时外向钾电流(Ito)的影响。方法成年雄性SD大鼠(180~200g)随机分为正常组、假手术组、心衰组和比索洛尔干预组,采用腹主动脉-下腔静脉穿刺造瘘法制作容量超负荷心衰模型。术后8周,比索洛尔干预组给予比索洛尔(1mg/kg,1次/日)灌胃,干预4周后,检测血流动力学及脑钠肽(BNP)以评价心功能。急性酶解法分离大鼠左室心肌细胞,采用全细胞膜片钳技术记录Ito电流,并绘制I-V曲线及激活、失活、恢复曲线。结果心衰组与假手术组大鼠比较,心功能明显下降,QTc间期明显延长(198.52±3.90ms vs.163.23±4.15ms,P0.01),Ito电流密度在-20m V~+90m V明显减小(P0.05),其失活过程延迟(V1/2:-34.60±0.40m V vs.-38.40±0.46m V;k:5.92±0.35 vs.7.78±0.41,P0.05),激活曲线及恢复曲线无明显变化。比索洛尔干预可明显改善心功能,缩短QTc(180.32±5.43ms vs.198.52±3.90ms,P0.01),增加Ito电流密度,改善失活过程(V1/2:-38.62±0.37m V vs.-34.60±0.40m V;k:6.7±0.3 vs.5.92±0.35,P0.05)。结论比索洛尔干预可改善慢性心衰大鼠的心功能,增加Ito电流密度。     

干细胞循环及其潜在应用前景

干细胞(stemcell)是胚胎发育过程中产生的或在个体成长中存留的一些能无限自我更新(self-renewing)并同时又能定向分化生成一系列组织的原始细胞。目前，据其来源分为胚胎干细胞和成体干细胞；按其分化能力分为全能干细胞(totipotent stem cell，TSC)和多能干细胞(multipotent stem cell，MSC)。一般认为胚胎干细胞为全能干细胞，而成体干细胞则多为多能干细胞。