细胞因子(IL-6、IL-10、TNF-α)在华支睾吸虫病肝功能损伤中作用的研究

目的探讨华支睾吸虫病患者白细胞介素-6(IL-6)、白细胞介素-10(IL-10)、肿瘤坏死因子-α(TNF-α)水平与肝功能的临床关系。方法试验组为50例未经治疗的华支睾吸虫病患者,并参照ChildPugh肝功能分级法,按照评分将其分成Ⅰ、Ⅱ、Ⅲ三组;对照组为20例健康献血员。采集试验组及对照组静脉血,用全自动生化分析仪检测血浆中总胆红素(TBIL)、血清白蛋白(ALB)和谷丙转氨酶(ALT)含量;采用放射免疫法检测血清IL-6、IL-10及TNF-α含量,并进行统计分析。结果华支睾吸虫病患者血清IL-6、IL-10、TNF-α水平明显高于健康人对照组(P0.01)。随着患者肝功能受累程度的加重,血清IL-6、IL-10及TNF-α含量依次递增,Ⅰ组和Ⅲ组间差异均有统计学意义(P0.01)。IL-6、TNF-α含量与其TBIL(γ=0.470、P0.01,γ=0.518、P0.01)及ALT(γ=0.497、P0.01,γ=0.285、P0.05)呈正相关,与ALB呈负相关(γ=-0.620、P0.01,γ=-0.665、P0.01)。结论华支睾吸虫病患者IL-6和TNF-α表达增强,共同参与介导了华支睾吸虫病肝损伤过程。     

医院医技人员对流行区华支睾吸虫病认知状况的调查

目的调查医院医技人员对流行区华支睾吸虫病的认知状况,为该病防治策略的制定提供依据。方法从华支睾吸虫流行病学、临床表现与并发症、诊断和治疗及相关知识的获得途径这几方面设置调查问卷,总分19分。对佳木斯市5家综合性医院和1家传染病专科医院医技人员进行匿名问卷调查。结果共发放问卷340份,回收有效问卷334份,有效应答率98.24%。334名医技人员最低得分2分,最高得分17分,平均得分(11.38±3.50)分(正确率59.89%)。其中5家综合医院医技人员平均得分(10.84±3.27)分,1家传染病专科医院医技人员平均得分(15.78±1.73)分,二者差异有统计学意义(t=14.353,P<0.001)。高级职称医技人员在流行病学、临床表现与并发症、诊断与治疗方面的得分均高于其他职称医技人员(均P<0.05)。结论佳木斯地区医技人员华支睾吸虫病总体认知率不高,应对不同医疗机构和职称的医技人员制定相应的培训内容,鼓励医技人员多途径获取华支睾吸虫病相关知识。     

肠道微生态在华支睾吸虫致宿主肝功能损伤中的作用研究

目的 研究肠道微生态在华支睾吸虫致肝损伤中的作用。方法 建立华支睾吸虫感染大鼠模型。分别在造模后48 h、18 d和35 d检测血浆内毒素、ALT（谷丙转氨酶）、AST（谷草转氨酶）水平;检测肠粘液中sIgA含量;取肠内容物进行乳酸杆菌、双歧杆菌、肠球菌和肠杆菌的培养及定量分析。结果 造模后18 d、35 d,大鼠血浆内毒素、ALT、AST水平明显升高,差异有统计学意义（t内=8.335、7.612,tALT=11.815、9.874,tAST7.433、8.015,P值均<0.01）;造模后48 h,肠黏液sIgA水平高于正常组（t=2.752,P<0.05）,尤以造模后18 d、35 d升高显著（t=13.118、9.546,P值均<0.01）;造模后48 h、18 d和35 d,肠道乳酸杆菌和双歧杆菌数量明显减少（t乳=2.612、4.142、5.556,t双2.302、4.565、3.982,P值<0.05或P值<0.01）,造模后18 d和35 d,肠杆菌和肠球菌数量明显增多（t肠=4.562、5.247,t肠=5.366、4.775,P值均<0.01）。结论 华支睾吸虫感染可致大鼠肠道菌群发生失调,引发内毒素血症,参与介导对肝细胞的损伤。     

凝血酶与血管内皮细胞

凝血酶不仅在凝血过程中起主导作用,还可以引发多种凝血酶受体介导的分子和细胞间相互作用,在动脉粥样硬化和再狭窄形成中起着重要的作用。现就凝血酶及其受体的特性,以及对血管内皮细胞的作用,包括通透性改变、内皮生长因子、基质金属蛋白酶、黏附分子表达作一综述。     

黄芪对急性白血病患者血清黏附分子水平影响的临床研究

目的:探讨黄芪对急性白血病病人可溶性细胞间黏附分子-1和可溶性血管细胞黏附分子-1水平的影响。方法:64例初治急性白血病患者随机分为化疗组32例和化疗加黄芪组32例,采用酶联免疫吸附测定方法(EuSA法),对治疗前后的血清可溶性细胞间黏附分子-1和可溶性血管细胞黏附分子-1水平进行检测。结果:①与正常组比较,急性白血病病人治疗前后可溶性细胞间黏附分子-1和可溶性血管细胞黏附分子-1水平升高(P<0 05)。②治疗后,化疗加黄芪组与化疗组血清可溶性细胞间黏附分子-1和可溶性血管细胞黏附分子-1水平均下降(P<0 05),化疗加黄芪组下降尤为明显(P<0 05)。结论黄芪可通过降低白血病血清sICAM-1和sVCAM-1水平的而发挥抗肿瘤作用。     

感染华支睾吸虫大鼠肠道菌群的实验研究

目的 观察华支睾吸虫感染对大鼠肠道菌群的影响.方法 建立华支睾吸虫感染大鼠模型,分别在造模后48 h、18d和35 d,取肠内容物进行乳酸杆菌、双歧杆菌、肠球菌和肠杆菌的培养及定量分析.结果 与对照组相比,在感染后48 h,大鼠肠道乳酸杆菌和双歧杆菌数量减少(P＜0.05),肠球菌和肠杆菌数量略有增加,但差异无统计学意义(P＞0.05);在感染后18 d(童虫期),乳酸杆菌、双歧杆菌数量进一步减少(P＜0.01),肠杆菌和肠球菌数量明显增加(P＜0.01);在感染后35 d(成虫期),四种肠道菌与童虫期的变化基本一致.结论 华支睾吸虫感染可致大鼠肠道菌群发生失调,其中益生菌减少,致病菌增多,尤以童虫期、成虫期较重.     

白念珠菌与血管内皮细胞黏附后的作用机制

白念珠菌与血管内皮细胞的相互作用是其是否造成血源性播散感染的中心环节,两者的黏附仅仅是作用的初级阶段、黏附的程度对两者作用的性质一感染控制和感染播散之间的关系并不明确。而在黏附后的相互作用研究中提示白念珠菌进入血管内皮细胞并造成其损伤继而进入其他组织,同时血管内皮细胞对白念珠菌感染也具有重要的保护作用,这种作用与血管内皮细胞对白念珠菌的内吞也密切相关。本文对两者黏附后血管内皮细胞对白念珠菌的吞噬,白念珠菌对血管内皮细胞的损伤以及血管内皮细胞对白念珠菌感染的保护作用方面作一综述。     

不同龄期华支睾吸虫囊蚴对猫寄生力的分析

采用捕获于华支睾吸虫病流行区的麦穗鱼,隔离饲养,用不同日龄囊蚴感染猫,感染后30d做解剖,收集成虫做统计分析的方法,进行了不同日龄寄生力分析。结果表明,0、379、762、1038日龄囊蚴感染的获虫率分别为43．07％、85．45％、4．51％、9．80％。结合国内资料,建立了计算华支睾吸虫囊蚴对猫寄生力的数学模型。     

华支睾吸虫感染对大鼠肠道菌群移位和内毒素血症的影响

目的 研究肠道细菌移位在华支睾吸虫病致病机制中的作用。方法 建立华支睾吸虫感染大鼠模型。分别在造模后48 h（后尾蚴期）、18 d（童虫期）和35 d（成虫期）,取肝、肺、淋巴结和血液组织,采用平板培养法进行细菌移位的检测;采用鲎三肽基质染色定量法检测血浆内毒素含量。结果 感染18 d后,实验组肠道细菌移位率开始增高,至感染35 d时,细菌移位率为70%,明显高于对照组的10%,差异有统计学意义（P=0.023＜0.05）;感染鼠以童虫期、成虫期细菌移位现象明显,总移位率为65%,与对照组10%比较,差异有统计学意义（u=3.59,P＜0.01）,且在肝、肺、淋巴结和血液组织中,移位发生率分别为60%、15%、25%和10%,以肝脏部位最高;造模后18 d血浆内毒素水平明显增高,造模后35 d血浆LPS水平略有下降,但仍明显高于对照组,差异有统计学意义（t=7.612,P＜0.01）。结论 华支睾吸虫感染可引发宿主肠道菌群移位,以肝组织多发,从而参与致病机制。     

凝血接触系统对人血管内皮细胞炎症活性的影响

内源性凝血途径的起始部分称为接触系统,包括高分子量激肽原、前激肽释放酶、XII因子和XI因子。以接触系统成分及激活产物分别刺激人血管内皮细胞,检测了其NF-κB活性、细胞间黏附分子1(ICAM-1)表达和炎性细胞因子分泌的变化。结果显示:与对照组相比较,只有游离XI因子和激活的XI因子可以使内皮细胞NF-κB活性升高,并具有统计学差异(P<0.01);而激活的XI因子能够进一步使内皮细胞的ICAM-1和细胞因子分泌显著增加(P<0.01)。其余各组与对照组相比没有统计学差异。这些观察结果提示接触系统可以直接活化血管内皮细胞,说明内源性凝血途径也参与了炎症的发展过程。     

急性脑梗死患者血管内皮功能及同型半胱氨酸水平的变化

目的 探讨急性脑梗死患者的治疗及其血管内皮功能、同型半胱氨酸水平变化。方法 选择延安大学附属医院2015年8月至2016年12月收治的98例急性脑梗死患者为观察组,选择同期进行体检的98例健康者为对照组。对比2组患者血管内皮功能、Hcy水平及治疗前后各项指标的变化情况。结果 治疗前观察组患者FMD、NO、eNOS水平显著低于对照组（t=－11.310、－7.669、－8.883,P0.05）;NIHSS评分下降,BI评分升高（t=10.954、－10.797,P<0.05）。结论 ACI患者血管内皮功能出现障碍,Hcy水平显著升高。叶酸及维生素B12临床疗效显著,可有效缓解血管内皮功能障碍,降低Hcy水平,改善患者预后。     

子痫前期患者肠道菌群变化与炎症反应和血管内皮功能的相关性

分析子痫前期患者肠道菌群变化与炎症反应和血管内皮功能的相关性,为该类患者的治疗提供参考。

选取我院2021年2月至2023年3月收治的子痫前期患者70例作为病例组,选取同期在本单位进行产检的健康妊娠妇女70例作为对照组,比较两组对象一般资料和肠道菌群数量;采用ELISA法检测血清炎症因子水平[C−反应蛋白（CRP）、肿瘤坏死因子（TNF-α）、白细胞介素-6（IL-6）、白细胞介素-8（IL-8）]和血管内皮功能相关因子[血管内皮生长因子（VEGF）、血管内皮素（ET）、一氧化氮（NO）、可溶性内皮因子（sEng）]水平;采用Pearson相关性分析肠道菌群与炎症反应和血管内皮功能的相关性。

两组对象年龄、妊娠前BMI、低密度脂蛋白胆固醇、高密度脂蛋白胆固醇、孕周、是否经产妇、妊娠胎数、是否妊娠糖尿病、流产史、吸烟史、饮酒史比较差异均无统计学意义（均P＞0.05）。病例组患者肠道大肠埃希菌、肠球菌数量均高于对照组,双歧杆菌、乳杆菌数量均低于对照组（均P＜0.05）。病例组患者血清CRP、IL-6、TNF-α、IL-8、NO、VEGF水平均高于对照组,而血清ET、sEng水平均低于对照组（均P＜0.05）。患者肠道大肠埃希菌、肠球菌数量与血清CRP、IL-6、TNF-α、IL-8、ET、sEng水平均呈正相关,与血清NO、VEGF水平均呈负相关（均P＜0.05）;患者肠道双歧杆菌、乳杆菌数量与血清CRP、IL-6、TNF-α、IL-8、ET、sEng水平均呈负相关,与血清NO、VEGF水平均呈正相关（均P＜0.05）。

子痫前期患者肠道菌群紊乱,炎症反应指标升高,血管内皮功能出现损伤,且肠道菌群变化与炎症反应、血管内皮功能具有显著相关性。

     

Platelet endothelial cell adhesion molecule‐1 (PECAM1) plays a critical role in the maintenance of human vascular endothelial barrier function

Cardiovascular endothelial barrier dysfunction is associated with a number of cardiovascular diseases. This study aims to investigate the role of platelet endothelial cell adhesion molecule‐1 (PECAM1) in the maintenance of the vascular endothelial barrier integrate. Human umbilical vein endothelial cells (HUVECs) were cultured into monolayers using as an in vitro model to assess the endothelial barrier function. Knockdown of the gene of PECAM1 markedly reduced the transendothelial resistance and increased the permeability of the HUVEC monolayers. From the wild HUVECs, we detected a complex of PECAM1, claudin1, occluding and endothelial cell selective adhesion molecule (ESAM); such a complex was not detected in the PECAM1‐deficient HUVECs. Knockdown of either claudin1, or occludin, or ESAM, did not affect the formation of the tight junction (TJ) complex. Exposure to recombinant interleukin (IL)‐13 inhibited the expression of PECAM1 and down‐regulated the HUVEC monolayer barrier function. PECAM1 plays an important role in the formation of TJ complex. Copyright © 2015 John Wiley & Sons, Ltd.     

神经细胞粘附分子

神经细胞粘附分子（ＮＣＡＭ）是一种糖蛋白,能介导细胞与细胞及细胞与细胞外基质间相互作用,它在细胞的识别及转移、肿瘤的浸润与生长、神经再生、跨膜信号的传导、学习和记忆等方面均起着一定的作用,本文对神经细胞粘附分子的结构、表达和功能加以概述,以增加对其的了解。     

Globular adiponectin induces adhesion molecule expression through the sphingosine kinase pathway in vascular endothelial cells

The signaling pathways that couple adiponectin receptors to functional, particularly inflammatory, responses have remained elusive. We report here that globular adiponectin induces endothelial cell activation, as measured by the expression of adhesion proteins such as vascular adhesion molecule-1 (VCAM-1), intracellular adhesion molecule-1 (ICAM-1), E-selectin and MCP-1, through the sphingosine kinase (SKase) signaling pathway. Treatment of human umbilical vein endothelial cells with globular adiponectin resulted in NF-kappaB activation and increased mRNA levels of VCAM-1, ICAM-1, E-selectin and MCP-1. Sphingosine 1-phosphate (S1P), but not ceramide or sphingosine, was a potent stimulator of adhesion protein expression. As S1P is generated from sphingosine by SKase, we treated cells with siRNA for SKase to silence the effects of S1P in the endothelial cells. Treatment with SKase siRNA inhibited globular adiponectin-induced NF-kappaB activation and markedly decreased the globular adiponectin-induced mRNA levels of adhesion protein. Thus, we demonstrated that the SKase pathway, through the generation of S1P, is critically involved in mediating globular adiponectin-induced endothelial cell activation.     

The role of the cytoskeleton in cellular adhesion molecule expression in tumor necrosis factor-stimulated endothelial cells

Leukocyte infiltration is a hallmark of the atherosclerotic lesion. These cells are captured by cellular adhesion molecules (CAMs), including vascular cell adhesion molecule-1 (VCAM-1), intercellular adhesion molecule-1 (ICAM-1), platelet-endothelial cell adhesion molecule (PECAM), and E-selectin, on endothelial cells (EC). We examined the role of the actin cytoskeleton in tumor necrosis factor-alpha (TNF-alpha)-induced translocation of CAMs to the cell surface. Human aortic EC were grown on 96-well plates and an ELISA was used to assess surface expression of the CAMs. TNF-alpha increased VCAM-1, ICAM-1, and E-selectin by 4 h but had no affect on the expression of PECAM. A functioning actin cytoskeleton was important for VCAM-1 and ICAM-1 expression as both cytochalasin D, an actin filament disruptor, and jasplakinolide, an actin filament stabilizer, attenuated the expression of these CAMs. These compounds were ineffective in altering E-selectin surface expression. Myosin light chains are phosphorylated in response to TNF-alpha and this appears to be regulated by Rho kinase instead of myosin light chain kinase. However, the Rho kinase inhibitor, Y27632, had no affect on TNF-alpha-induced CAM expression. ML-7, a myosin light chain kinase inhibitor, had a modest inhibitory effect on the translocation of VCAM-1 but not on ICAM-1 or E-selectin. These data suggest that the surface expression of VCAM-1 and ICAM-1 is dependent on cycling of the actin cytoskeleton. Nevertheless, modulation of actin filaments via myosin light chain phosphorylation is not necessary. The regulation of E-selectin surface expression differs from that of the other CAMs.     

Endothelial intercellular cell adhesion molecule 1 contributes to cell aggregate formation in CHO cells cultured in serum-free media

Chinese hamster ovary (CHO) cells have been adapted to grow in serum-free media and in suspension culture to facilitate manufacturing needs. Some CHO cell lines, however, tend to form cell aggregates while being cultured in suspension. This can result in reduced viability and capacity for single cell cloning (SCC) via limiting dilution, and process steps to mitigate cell aggregate formation, for example, addition of anti-cell-aggregation agents. In this study, we have identified endothelial intercellular cell adhesion molecule 1 (ICAM-1) as a key protein promoting cell aggregate formation in a production competent CHO cell line, which is prone to cell aggregate formation. Knocking out (KO) the ICAM-1 gene significantly decreased cell aggregate formation in the culture media without anti-cell-aggregation reagent. This trait can simplify the process of transfection, selection, automated clone isolation, and so on. Evaluation in standard cell line development of ICAM-1 KO and wild-type CHO hosts did not reveal any noticeable impacts on titer or product quality. Furthermore, analysis of a derived nonaggregating cell line showed significant reductions in expression of cell adhesion proteins. Overall, our data suggest that deletion of ICAM-1 and perhaps other cell adhesion proteins can reduce cell aggregate formation and improve clonality assurance during SCC.     

Homocysteine-thiolactone induces caspase-independent vascular endothelial cell death with apoptotic features

Objective. Cell death is generally classified into two large categories: apoptosis, which represents active, physiological programmed cell death, and necrosis, which represents passive cell death without underlying regulatory mechanisms. Apoptosis plays an important role in tissue homeostasis and its role in endothelium integrity can be influenced by the functional status of endothelial cells. Homocysteine, a sulfated amino-acid product of methionine demethylation, is an independent risk factor for vascular disease (arterial and venous thombosis). Our goal was to investigate the thiol-derivatives effect on the endothelial cell apoptosis. Methods. Three parameters were measured: mitochondrial membrane potential using DiOC₆(3) as the probe, DEVDase activation, and phosphatidylserine exposure on the cell surface with fluorosceinated annexin V labeling which allows apoptosis to be distinguished from necrosis. Results. Homocysteine-thiolactone induced endothelial cell apoptosis in a concentration-dependent manner (range: 50–200 M), independently of the caspase pathway. Only homocysteine-thiolactone, among the thiol derivatives tested, induced apoptosis. Apoptosis was not influenced by the serum concentration in culture medium, suggesting that the observed apoptotic process could occur in vivo. None of the inhibitors used (e.g., leupeptin, fumosinin Bl, catalase, or z-VAD-fmk) was able to prevent homocysteine-induced apoptosis of vascular endothelial cells. Conclusion. The apoptosis of vascular endothelial cells induced by high concentration of homocysteine-thiolactone might be one step atherosclerotic cardiovascular disease, and contribute to its complication.     

The effect and action mechanism of resveratrol on the vascular endothelial cell by high glucose treatment

To investigate the effect and action mechanism of resveratrol on the vascular endothelial cell by high glucose treatment. Primarily cultured human umbilical vein endothelial cells (HUVECs) were pretreated by resveratrol (0.2 μmol/L) and holding for 6 h, and then cultured in Dulbecco Modified Eagle Medium (DMEM) within 0.45 mmol/L of palmimte acid and 32.8 mmol/L of glucose, which is holding for 12 h. The cells were collected to analyze the expression of E-selected element. Supernatant of cultured cells, induced by 100 nmol/L insulin for 30 min, was used to analyze the nitric oxide content. Compared with normal control cells, the secretion of nitric oxide is stimulated by insulin decrease, however, the expression of E-selected element increased in HUVEC. Resveratrol treatment increased the secretion of nitric oxide stimulated by insulin and decreased the expression of E-selected element and partly counteracts the impairment of high glucose and palmitate acid on the function of endothelial cells. Resveratrol can improve and protect the function of high glucose and fatty acid cultured endothelial cell, and therefore may be a promising medicine in the prevention or therapy of diabetic macrovascular diseases.