冠状动脉搭桥材料的内皮细胞分泌的一氧化氮和内皮素水平研究

目的检测冠状动脉搭桥患者桡动脉和大隐静脉内皮细胞所分泌的一氧化氮(NO)和内皮素(ET)水平,并与脐静脉内皮细胞相比较,了解内皮细胞的功能。方法利用剩余的冠状动脉搭桥移植材料,采用Ⅱ型胶原酶消化的方法获取内皮细胞并培养,收集培养细胞的上清液,利用试剂盒检测内皮细胞分泌的NO和ET水平。结果与人正常脐静脉内皮细胞相比,冠状动脉搭桥材料桡动脉和大隐静脉内皮细胞分泌的NO水平显著降低(P<0.05),ET水平显著增高(P<0.05)。结论冠状动脉搭桥患者桡动脉和大隐静脉的内皮细胞与脐静脉内皮细胞相比,所分泌的NO和ET差异有统计学意义,冠状动脉搭桥患者搭桥材料的内皮细胞分泌功能可能存在功能障碍。     

脂质过氧化损伤诱导培养的人脐静脉内皮细胞表达细胞间粘附分子1

为探讨脂质过氧化损伤能否诱导血管内皮细胞表达细胞间粘附分子 1,用胰酶消化法分离人脐静脉内皮细胞进行原代培养 ,内皮细胞用不同浓度联胺作用相同时间或同一浓度联胺作用不同时间 ,使之发生脂质过氧化损伤 ,逆转录聚合酶链反应检测内皮细胞细胞间粘附分子 1mRNA表达 ,细胞酶链免疫吸附实验测定内皮细胞细胞间粘附分子 1蛋白表达。逆转录聚合酶链反应结果发现 ,不同浓度联胺 (1μmol L、5 μmol L和 10 μmol L)作用 8h ,内皮细胞细胞间粘附分子 1对 β actin吸光度比值依次为 0 .5 35、0 .90 8和 1.186 ,分别是对照组 (0 .185 )的 2 .89倍、4 .91倍和 6 .4 1倍 ;而同一浓度联胺 (5 μmol L)作用 4h和 2 4h ,吸光度比值依次为 0 .5 98和 1.2 92 ,分别是对照组 (0 .185 )的 3.2 3倍和 6 .98倍。细胞酶链免疫吸附实验结果发现 ,经 1μmol L、5 μmol L和 10 μmol L联胺作用 4h后 ,内皮细胞细胞间粘附分子 1蛋白表达的吸光度值依次为 0 .1387、0 .1775和 0 .2 32 6 ,分别是对照组 (0 .10 35 )的 1.34倍、1.71倍和 2 .2 5倍 (P <0 .0 1)。结果表明 ,联胺诱导的内皮细胞细胞间粘附分子 1的表达在一定作用时间和浓度范围内呈时间和剂量依赖性。提示联胺诱导的脂质过氧化损伤可能上调细胞间粘附分子 1mRNA和     

Resistance Exercise Restores Endothelial Function and Reduces Blood Pressure in Type 1 Diabetic Rats

Background

Resistance exercise effects on cardiovascular parameters are not consistent.

Objectives

The effects of resistance exercise on changes in blood glucose, blood pressure and vascular reactivity were evaluated in diabetic rats.

Methods

Wistar rats were divided into three groups: control group (n = 8); sedentary diabetic (n = 8); and trained diabetic (n = 8). Resistance exercise was carried out in a squat device for rats and consisted of three sets of ten repetitions with an intensity of 50%, three times per week, for eight weeks. Changes in vascular reactivity were evaluated in superior mesenteric artery rings.

Results

A significant reduction in the maximum response of acetylcholine-induced relaxation was observed in the sedentary diabetic group (78.1 ± 2%) and an increase in the trained diabetic group (95 ± 3%) without changing potency. In the presence of NG-nitro-L-arginine methyl ester, the acetylcholine-induced relaxation was significantly reduced in the control and trained diabetic groups, but not in the sedentary diabetic group. Furthermore, a significant increase (p < 0.05) in mean arterial blood pressure was observed in the sedentary diabetic group (104.9 ± 5 to 126.7 ± 5 mmHg) as compared to that in the control group. However, the trained diabetic group showed a significant decrease (p < 0.05) in the mean arterial blood pressure levels (126.7 ± 5 to 105.1 ± 4 mmHg) as compared to the sedentary diabetic group.

Conclusions

Resistance exercise could restore endothelial function and prevent an increase in arterial blood pressure in type 1 diabetic rats.     

The impact of rapid atrial pacing on ADMA and endothelial NOS

Background

The endothelial nitric oxide synthase (eNOS) inhibitor asymmetric dimethylarginine (ADMA) is a well-established risk factor for oxidative stress, vascular dysfunction, and congestive heart failure. The aim of the present study was to determine the impact of rapid atrial pacing (RAP) on ADMA levels and eNOS expression.

Methods and results

ADMA levels were studied in 60 age- and gender-matched patients. Thirty five patients had persistent atrial fibrillation (AF) ≥ 4 months. In AF-patients, parameters were studied before and 24 h after electrical cardioversion. Moreover, ADMA, eNOS expression, and calcium-handling proteins were studied in pigs subjected to RAP as well as in endothelial cell (EC) cultures. ADMA level was significantly higher in AF compared to sinus rhythm patients (p = 0.024). ADMA was highest in AF-patients, who also showed elevated troponin T (TnT) levels. Moreover, ADMA showed a significant linear correlation to TnT (r = 0.47; p < 0.01). After electrical cardioversion ADMA returned to normal within 24 h. In pigs, RAP for 7 h increased ADMA levels (p = 0.018) and TnI (p < 0.05), and reduced mRNA expression of ventricular and aortic eNOS (− 80%; p < 0.05) compared to sham-control. However, ADMA per se did not affect eNOS mRNA level in EC cultures.

Conclusion

The current study shows that acute and persistent episodes of atrial tachyarrhythmia are associated with elevated ADMA levels accompanied by increased ischemic myocardial markers. Moreover, RAP increases ADMA and down-regulates eNOS expression in an ADMA-independent manner. We conclude that the combination of these two separate and potentially synergistic mechanisms may contribute to long-term vascular injury during atrial tachyarrhythmia.     

Neuroprotective effects of progesterone in traumatic brain injury: blunted in vivo neutrophil activation at the blood-brain barrier

Background

Progesterone (PRO) may confer a survival advantage in traumatic brain injury (TBI) by reducing cerebral edema. We hypothesized that PRO reduces edema by blocking polymorphonuclear (PMN) interactions with endothelium (EC) in the blood-brain barrier (BBB).

Methods

CD1 mice received repeated PRO (16 mg/kg intraperitoneally) or vehicle (cyclodextrin) for 36 hours after TBI. Sham animals underwent craniotomy without TBI. The modified Neurological Severity Score graded neurologic recovery. A second craniotomy allowed in vivo observation of pial EC/PMN interactions and vascular macromolecule leakage. Wet/dry ratios assessed cerebral edema.

Results

Compared with the vehicle, PRO reduced subjective cerebral swelling (2.9 ± .1 vs 1.2 ± .1, P < .001), PMN rolling (95 ± 1.8 vs 57 ± 2.0 cells/100 μm/min, P < .001), total EC/PMN adhesion (2.0 ± .4 vs .8 ± .1 PMN/100 μm, P < .01), and vascular permeability (51.8% ± 4.9% vs 27.1% ± 4.6%, P < .01). TBI groups had similar a Neurological Severity Score and cerebral wet/dry ratios (P > .05).

Conclusions

PRO reduces live pericontusional EC/PMN and BBB macromolecular leakage after TBI. Direct PRO effects on the microcirculation warrant further investigation.     

冠状动脉慢血流现象患者内皮功能的研究

目的 探讨冠状动脉慢血流(CSF)现象患者的内皮功能.方法 我院2006年1月-2007年3月因可疑冠心病行冠状动脉造影检查显示冠状动脉无明显病变的患者60例,采用TMI记帧法记录各支冠状动脉的TMI帧数,冠状动脉平均的TMI帧数＞27为CSF,将患者分为CSF组(28例)和对照组(32例).所有患者分别于冠状动脉造影术24h后取血,行血清一氧化氮(NO)、血浆内皮素-1(ET-1)测定.结果 CSF组患者血NO 水平显著低于对照组,ET-1水平高于对照组,两组比较差异均有统计学意义(P＜0.05).结论 CSF患者可能存在内皮功能障碍,内皮功能障碍发生的病理生理机制可能参与CSF现象发生的病理生理过程中.     

Association between endothelial dysfunction and arterial stiffness in continuous ambulatory peritoneal dialysis patients

Objective To investigate the association between endothelial dysfunction and arterial stiffness in continuous ambulatory peritoneal dialysis （CAPD） patients. Methods Ninety-four stable CAPD patients from a single center were enrolled in this cross-sectional study. Ultrasound evaluation was conducted on brachial artery to estimate endothelial-dependent flow-mediated dilation (FMD). Automatice pulse wave velocity (PWV) measuring system was applied to examine the carotid-femoral PWV. Blood pressure and biochemical parameters were detected. Pearson's correlation and Stepwise multiple regression analysis were performed to explore the relationship between FMD and PWV. Results PWV was significantly higher in patients with diabetes as compared to those without diabetes[(13.25±1.66) m/s vs (11.24±1.92) m/s, P＜0.01]. Furthermore, PWV was positively correlated with age(r＝0.319, P＝0.002), SBP (r＝0.289, P＝0.005) and C-reactive protein (r＝0.211, P＝0.041), was negatively correlated with albumin (r＝-0.429, P＝0.001) and FMD (r＝-0.466, P＝0.001). In multivariate regression analysis, diabetes mellitus, albumin, FMD, age and SBP were independently associated with PWV after adjustment. Conclusion Endothelial dysfunction is associated with greater arterial stiffness in CAPD patients.     

血管化肋软骨结合纤毛化内皮内壁的人工气管重建

目的：探讨血管化肋软骨结合纤毛化内皮内壁合成人工气管重建气管长段及特殊缺损的可行性,建立与天然气管的生理结构、功能更接近的人工气管模型。方法以8例新西兰白兔为动物实验模型,I期颈部双层带血供筋膜包埋培养自体肋软骨和鼻中隔黏膜,II期人工气管原位移植,术后定期评估生理、呼吸及病理学等指标。结果8例实验兔II期术后平均存活时间21.9 d,死亡原因为呼吸困难。人工气管组织解剖可见瘢痕增生,无塌陷,有弹性和硬度。组织病理可见肋软骨和气管环软骨在组织学上有较高相似度;肋软骨在带血供筋膜包裹培养下均未被吸收,仍可见肋软骨组织;鼻中隔黏膜在体内加压及带血供筋膜营养下继续分化,HE染色切片下可见人工气管内壁覆有上皮样组织。结论肋软骨可作为制备人工气管塑形材料;包裹肋软骨的带血供筋膜可提供充足的血供,弥补了游离培养肋软骨致其吸收的缺陷;鼻中隔黏膜在体内加压及带血供筋膜的营养下,有望模拟气管纤毛上皮,从而发挥其与气管内壁相似的生物学特性。     

Modulation of ATP/ADP Concentration at the Endothelial Surface by Shear Stress: Effect of Flow Recirculation

The extracellular presence of the adenine nucleotides ATP and ADP induces calcium mobilization in vascular endothelial cells (ECs). ATP/ADP concentration at the EC surface is determined by a balance of convective-diffusive transport to and from the EC surface, hydrolysis by ectonucleotidases at the cell surface, and flow-induced ATP release from ECs. Our previous numerical simulations in a parallel plate geometry had demonstrated that flow-induced ATP release has a profound effect on nucleotide concentration at the EC surface. In the present study, we have extended the modeling to probe the impact of flow separation and recirculation downstream of a backward facing step (BFS) on ATP/ADP concentration at the EC surface. The results show that for both steady and pulsatile flow over a wide range of wall shear stresses, the ATP + ADP concentration at the EC surface is considerably lower within the flow recirculation region than in areas of undisturbed flow outside the recirculation zone. Pulsatile flow also leads to sharp temporal gradients in nucleotide concentration. If confirmed experimentally, the present findings suggest that disturbed and undisturbed flow may affect EC calcium mobilization differently. Such differences might, in turn, contribute to the observed endothelial dysfunction in regions of disturbed flow.     

心房颤动患者左心房血清炎性因子和血管内皮损伤标志物水平变化与血栓的相关性研究

背景 心房颤动（以下简称房颤）容易合并脑卒中和外周动脉栓塞。研究房颤血栓形成的具体机制并进行有效干预以降低血栓形成的风险,是目前房颤基础和临床研究的重要方向。 目的 探讨房颤患者左心房血清炎性因子和血管内皮损伤标志物水平变化与血栓的相关性。 方法 选取2017年7月至2019年12月在广西医科大学第一附属医院接受开胸心脏手术的瓣膜性心脏病患者29例和冠心病患者10例,依据心律情况分为窦性心律组15例和房颤组24例。房颤组的24例患者再依据血栓情况分为无左心耳血栓和有左心耳血栓两个亚组,分别为房颤+左心耳血栓亚组和房颤无左心耳血栓亚组,各12例。收集患者的一般资料,并检测左心房内径（LAD）、左心室射血分数（LVEF）,术中抽取左心房血液标本检测蛋白激酶B（AKT）、核转录因子κB（NF-κB）、超敏C反应蛋白（hs-CRP）、白介素（IL）-6、IL-8、肿瘤坏死因子α（TNF-α）、内皮素（ET-1）、一氧化氮（NO）、血管性血友病因子（vWF）、细胞间黏附分子（ICAM-1）及血管细胞黏附因子（VCAM-1）水平,并检测房颤+左心耳血栓亚组患者血栓面积。房颤+左心耳血栓亚组患者LAD、LVEF、炎性因子水平和血管内皮损伤标志物的水平与左心耳血栓面积的关系采用Pearson相关分析。 结果 窦性心律组、房颤无左心耳血栓亚组与房颤+左心耳血栓亚组患者LAD、LVEF比较,差异有统计学意义（P<0.05）;房颤无左心耳血栓亚组和房颤+左心耳血栓亚组患者LAD、LVEF比较,差异无统计学意义（P>0.05）。房颤无左心耳血栓亚组患者AKT、NF-κB、IL-8、ET-1、ICAM-1、VCAM-1水平高于窦性心律组,NO水平低于窦性心律组（P<0.05）。房颤+左心耳血栓亚组患者AKT、hs-CRP水平高于房颤无左心耳血栓亚组,NO水平低于房颤无左心耳血栓亚组（P<0.05）;房颤无左心耳血栓亚组和房颤+左心耳血栓亚组患者NF-κB、IL-6、IL-8、TNF-α、ET-1、vWF、ICAM-1、VCAM-1水平比较,差异无统计学意义（P>0.05）。房颤+左心耳血栓亚组患者血栓面积最大为4.8 cm2,最小为1.67 cm2,平均为（3.48±0.83）cm2。Pearson相关分析结果显示,房颤合并左心耳血栓患者LAD、LVEF、AKT、NF-κB、hs-CRP、IL-6、IL-8、TNF-α、ET-1、NO、vWF、ICAM-1、VCAM-1与血栓面积无直线相关关系（P>0.05）。 结论 房颤患者左心房血液炎性因子和血管内皮损伤标志物水平明显升高,且合并左心房血栓时上述指标更高。检测炎性因子和血管内皮损伤标志物的水平有助于评估房颤患者的血栓状态。