Differential effect of simvastatin on activation of Rac(1) vs. activation of the heat shock protein 27-mediated pathway upon oxidative stress,in human smooth muscle cells

In the present study, we have analyzed the response of human smooth muscle cell (SMC)s to oxidative stress, in terms of recruitment of key elements of the stress-activated protein kinase (SAPK) pathway, such as Rac(1), p38, and the small heat shock protein (HSP)27. The level of expression of three small HSPs, alphaB-crystallin, HSP20, HSP27, as well as the phosphorylation levels of HSP27 and p38, were higher in cultured, asynchronously growing SMCs originating from left interior mammary artery (LIMA) than those originating from aorta, saphenous vein, and umbilical vein, validating the choice of SMCs from LIMA as a model system in our study. In synchronized, quiescent SMCs from LIMA, oxidative stress (H(2)O(2) stimulation)-induced membrane translocation of Rac(1), p38 phosphorylation, membrane translocation, and phosphorylation of HSP27. In these cells, simvastatin (S), an HMG-CoA reductase inhibitor, blocked, in a mevalonate-dependent way, oxidative stress-induced membrane translocation of Rac(1). However, S pretreatment prior to oxidative stress increased the levels of p38 phosphorylation, HSP27 membrane translocation/phosphorylation, actin polymerization, and apoptosis in these cells, in a mevalonate-dependent way. These results establish that S pretreatment has a stimulatory effect on the stress-activated p38/HSP27 pathway, despite its blocking effect on Rac(1) activation.     

辛开苦降法对FD大鼠血浆MTL、胃体MTL、ICC及SMC影响的实验研究

Cajal间质细胞(interstitial cells of Cajal,ICC)是胃肠运动的起搏细胞,神经元细胞接受中枢神经系统的信号后传递给ICC,再作用于平滑肌细胞(SMC),从而维持正常的胃肠运动.胃动素(MTL)是目前公认启动胃肠收缩活动的兴奋性脑肠肽,神经冲动传至ICC后可作用于兴奋性神经元产生兴奋性连接电位(excitory junction potential,EJP),使平滑肌细胞产生去极化[1-2].     

染色体结构维持蛋白4在胰腺癌中表达的临床与生物信息学分析

目的 研究染色体结构维持蛋白4(structural maintenance of chromosome 4,SMC4)在胰腺癌组织中的表达差异及其与临床病理特征和预后的关系,并探讨其可能发生相互作用的蛋白网络及调控的可能信号通路.方法 采用Western blotting检测中国人民解放军中部战区总医院收集的12例胰...     

前列腺素E1对人肠系膜动脉平滑肌细胞钙激活钾通道活动的影响

目的：探讨前列腺素E1（PGE1）对人肠系膜动脉平滑肌细胞钙激活钾通道（KCa）活动的影响。方法：选择因消化道疾病手术而无血管病变的患者的肠系膜动脉小分支,用酶消化法获得单个平滑肌细胞（SMC）,应用膜片钳技术观察PGE1对KCα的影响。结果：在内面向外膜片下,PGE1可使KCa开放概率（Po）增加,平均开放时间（To）延长,平均关闭时间（Tc）缩短,并增大单通道电流幅值。结论：PGE1激活KCa,增加K^ 外流,引起细胞膜超极化从而舒张血管。     

天鹅记忆接骨器对实验性骨折愈合中皮质骨血供的影响

目的:观察天鹅记忆接骨器(SMC)对实验性骨折愈合局部血供的影响,探讨SMC促进骨愈合的机理。方法:50只新西兰大白兔双侧肱骨干截骨后,随机选取一侧用SMC固定,对侧用4孔动力加压接骨板(DCP)固定。分别在术后3d,2、4、8、12周时,行微血管碳素墨水造影和放射微球法测定,观察两组固定对骨皮质再血管化过程和局部微循环的影响。结果:SMC组血管再生主要来源于髓内侧,皮质骨再血管化速度明显快于DCP组。SMC组从术后2周开始血流量即开始回升,而DCP组从术后4周才开始回升。术后8周以后,SMC组血供已完全恢复正常,而DCP组一直到术后12周,血供仍未达到正常水平(P<0.05)。结论:SMC具有特殊的空间构型和材质特性,不仅能对骨折形成牢固的固定,而且对骨干血供的损伤较轻,有利于皮质骨的再血管化。     

木贼提取物对大鼠动脉粥样硬化早期血管平滑肌细胞增殖与凋亡的影响

目的研究木贼正丁醇提取物对大鼠动脉粥样硬化（AS）早期主动脉平滑肌细胞增殖及凋亡的影响。方法选用雄性SD大鼠，随机分为正常对照、模型、阻性药对照及提取物组。复制食饵性AS早期模型，同时给予提取物预防性给药。以吉非罗齐为阳性药对照。实验9w，观察主动脉壁病理形态学变化，流式细胞术定量检测主动脉壁平滑肌增殖及凋亡率。结果木贼正丁醇提取物组平滑肌凋亡率明显高于模型组（P〈0．01），增殖指数低于模型组（P〈0．01）。结论木贼正丁醇提取物可促进AS早期平滑肌凋亡，抑制其增殖，具有阻断AS早期病变进展的作用。     

Vascular endothelial growth factors: biology and current status of clinical applications in cardiovascular medicine

Members of the vascular endothelial growth factor (VEGF) family are among the most powerful modulators of vascular biology. They regulate vasculogenesis, angiogenesis, and vascular maintenance during embryogenesis and in adults. Because of their profound effects on blood vessels, VEGFs have received much attention regarding their potential therapeutic use in cardiovascular medicine, especially for therapeutic vascular growth in myocardial and peripheral ischemia. However, completed randomized controlled VEGF trials have not provided convincing evidence of clinical efficacy. On the other hand, recent preclinical proangiogenic VEGF studies have given insight, and anti-VEGF studies have shown that the disturbance of vascular homeostasis by blocking VEGF-A may lead to endothelial dysfunction and adverse vascular effects. Excess VEGF-A may contribute to neovascularization of atherosclerotic lesions but, currently, there is no evidence that transient overexpression by gene transfer could lead to plaque destabilization. Here, we review the biology and effects of VEGFs as well as the current status of clinical applications and future perspectives of the therapeutic use of VEGFs in cardiovascular medicine.