The vascular endothelium plays a role in insulin action

The endocrine system relies on the vasculature for delivery of hormones throughout the body, and the capillary microvasculature is the site where the hormones cross from the blood into the target tissue. Once considered an inert wall, various studies have now highlighted the functions of the capillary endothelium to regulate transport and therefore affect or maintain the interstitial environment. The role of the capillary may be clear in areas where there is a continuous endothelium, yet there also appears to be a role of endothelial cells in tissues with a sinusoidal structure. Here we focused on the most common endocrine disorder, diabetes, and several of the target organs associated with the disease, including skeletal muscle, liver and pancreas. However, it is important to note that the ability of hormones to cross the endothelium to reach their target tissue is a component of all endocrine functions. It is also a consideration in organs throughout the body and may have greater impact for larger hormones with target tissues containing a continuous endothelium. We noted that the blood levels do not always equal interstitial levels, which is what the cells are exposed to, and discussed how this may change in diseases such as obesity and insulin resistance. The capillary endothelium is, therefore, an essential and understudied aspect of endocrinology and metabolism that can be altered in disease, which may be an appropriate target for treatment.     

反义细胞外信号调节激酶对移植物血管的保护作用

目的探讨反义细胞外信号调节激酶（ERK1／2）基因治疗对移植物血管的保护作用及可能的保护机制。方法建立BN至Lewis大鼠的腹主动脉移植模型。反义ERK1／2治疗组移植前取供者动脉血管段给予经脂质体包装的反义ERK1／2基因转染；腹主动脉移植术后1个月内受者每日从尾静脉或阴茎背静脉注入经脂质体包装的反义ERK1／2寡核苷酸100μl。对照组移植未经任何处理的血管段，移植后也无特殊处理。移植术后60d取移植段主动脉进行组织病理学观察内膜和胶原纤维变化；免疫组织化学法观察移植段血管ERK1／2基因的表达和CD4^＋、CD8^＋T淋巴细胞的浸润情况；ELISA法检测血清中细胞间粘附分子（ICAM-1）的变化。结果移植术后60d，对照组的移植动脉呈慢性移植物血管病表现，血管内膜显著增厚，移植血管中ERK1／2基因高表达，CD4^＋、CD8^＋T淋巴细胞大量浸润；反义ERK1／2基因治疗组移植动脉呈血管内膜炎改变，ERK1／2基因表达不明显，内膜有少量CD4^＋、CD8^＋T淋巴细胞；对照组ICAM-1表达显著高于反义ERK1／2治疗组（P〈0．05）。结论反义ERK1／2基因治疗对移植物血管具有保护作用，可以减缓慢性移植物血管病的发生，这种保护机制可能和减少ICAM-1的表达以及减少移植血管T淋巴细胞的浸润有关。     

阿尔茨海默病与血管性因素的关系探讨

目的探讨阿尔茨海默病（AD）与血管性因素之间的关系。方法选取解放军总医院临床诊断可能的AD患者91例，以性别、职业和受教育程度相匹配的认知功能正常老年人155例为对照，以Logistic回归模型分析各种血管性因素与AD的关系。结果单因素分析显示，起搏器心律、贫血、冠心病、慢性阻塞性肺疾病、脑卒中、心律失常、短暂性脑缺血发作、心脏传导阻滞、高脂血症、糖尿病史、婚姻状况及年龄与AD有关，OR值范围为12．83～1．18。多因素分析校正了年龄和婚姻状况的影响后，证实贫血、冠心病和脑卒中史与AD有关，OR值（95％可信区间）依次为4．87（2．12～11．22）、2．94（1．38～6．27）、2．44（1．28～4．64）。结论AD与血管性因素有关，贫血、冠心病和脑卒中史可能是AD的独立危险因素。     

Ex Vivo Application of Carbon Monoxide in University of Wisconsin Solution to Prevent Intestinal Cold Ischemia/Reperfusion Injury

Carbon monoxide (CO), a byproduct of heme catalysis, was shown to have potent cytoprotective and anti-inflammatory effects. In vivo recipient CO inhalation at low concentrations prevented ischemia/reperfusion (I/R) injury associated with small intestinal transplantation (SITx). This study examined whether ex vivo delivery of CO in University of Wisconsin (UW) solution could ameliorate intestinal I/R injury. Orthotopic syngenic SITx was performed in Lewis rats after 6 h cold preservation in control UW or UW that was bubbled with CO gas (0.1-5%) (CO-UW). Recipient survival with intestinal grafts preserved in 5%, but not 0.1%, CO-UW improved to 86.7% (13/15) from 53% (9/17) with control UW. At 3 h after SITx, grafts stored in 5% CO-UW showed improved intestinal barrier function, less mucosal denudation and reduced inflammatory mediator upregulation compared to those in control UW. Preservation in CO-UW associated with reduced vascular resistance (end preservation), increased graft cyclic guanosine monophosphate levels (1 h), and improved graft blood flow (1 h). Protective effects of CO-UW were reversed by ODQ, an inhibitor of soluble guanylyl cyclase. In vitro culture experiment also showed better preservation of vascular endothelial cells with CO-UW. The study suggests that ex vivo CO delivery into UW solution would be a simple and innovative therapeutic strategy to prevent transplant-induced I/R injury.     

机械压力对人脐静脉内皮细胞ET-1、NO合成的影响和意义

目的探讨压力增高对血管内皮细胞分泌血管活性物质功能的影响及其在门静脉高压症发病机制中的作用。方法用RT-PCR方法半定量研究人脐静脉内皮细胞ET-1、eNOS、i-NOS mRNA的表达;用硝酸还原酶法检测各组细胞培养液中NO代谢产物NO2-/NO3-的含量,免疫荧光标记激光扫描共聚焦显微镜检测培养细胞的ET-1蛋白表达。结果ET-1和eNOS mR-NA在正常培养的内皮细胞中即有表达,iNOS mRNA则几乎无表达。生理水平压力刺激下各组各待测基因mRNA表达与对照组无显著性差异。超生理范围压力刺激后,ET-1 mRNA有显著性升高。eNOS mRNA在40 mm Hg 24 h后才有显著性差异。iNOS mRNA在不同条件下均无显著变化。在细胞培养液中分别加入细胞外钙螯合剂EGTA、PKC抑制剂后,则见ET-1、eNOS mRNA表达下降。结论压力增高可刺激血管内皮细胞合成ET-1、NO,其作用在转录水平,其作用机制分别与PKC信号通路和细胞外钙浓度有关。门静脉压力增高与血管内皮细胞合成ET-1、NO增多之间存在相互作用。