血管通透性增高的基本机制

The increased microwascular permeability appears msinly in venule during inflammation,shock,and bums.Endothelial cells play an important role in venule permeability enhancement.There are two kinds of pathway for macromolecule extravasation.One is paracellular pathway and another is transcellular pathway,which are related to the formation of endothelial gap or transcellular openings seperately.The alter-ation of intercellular reated portein,such as occludin,claudin,zona occludens(ZO),junctional adhesion molecule(JAM),VE-cadherin,catenin,integrin,etc,and the alteration of endothelial cytoskeleton,such as rearrangement of actin filament,formation of stress fiber and focal ahdesion,etc,involve in the pathogenesis of increased microvascular permeability.     

体外震波对骨微血管内皮细胞生理功能的影响

BACKGROUND: Extracorporeal shock wave has been shown to influence the physiological function of endothelial cells via the activation of mechanoreceptors and specific signal transduction system, and gene expression regulation. OBJECTIVE:To explore the impact of different energy flow densities and numbers of shots of extracorporeal shock waves on the new vessel formation ability, migration capability and apoptosis of bone microvascular endothelial cells. METHODS: Bone microvascular endothelial cells isolated from the femoral head of patients undergoing arthroplasty were subcultured in vitro, and then were immunofluorescently evaluated with endothelial cell marker antibodies to CD31 and von Willebrand factor (vWF), and grouped according to different energy flow densities (low, 0.03 mJ/mm2; high, 0.11 mJ/mm2) and numbers of shots (400 and 800). Capillary-like tube formation, migration capability and apoptosis of bone microvascular endothelial cells were determined by 3-D culture in vitro, scratch test, and flow cytometry, respectively. RESULTS AND CONCLUSION: vWF and CD31 were positively expressed in approximately 100% of bone microvascular endothelial cells, which indicates the cultured cells had characterization of microvascular endothelial cells. Extracorporeal shock wave enhanced angiogenesis and migration capability of bone microvascular endothelial cells derived from the femoral head, and especially low-energy flow density of extracorporeal shock wave exerted more superior effects. Angiogenesis of bone microvascular endothelial cells was decreased with the increased shot number in the low-energy flow density group. In addition, extracorporeal shock wave inhibited bone microvascular endothelial cell apoptosis induced by steroids. Our results suggest that energy flow density and number of shots of extracorporeal shock waves impact the physiological function of bone microvascular endothelial cells derived from the femoral head. 中国组织工程研究杂志出版内容重点：组织构建;骨细胞;软骨细胞;细胞培养;成纤维细胞;血管内皮细胞;骨质疏松;组织工程     

Relaxin protects myocardial microvascular endothelial cells from hypoxia-reoxygenation injury北大核心

BACKGROUND: Relaxin can significantly improve cardiac and renal dysfuction caused by pathological factors, inhibit myocardial hypertrophy, have an anti-fibrosis effect, and improve ischemia-reperfusion injury. However, its protective mechanism against hypoxia-reoxygenation injury of endothelial cells remains unclear. OBJECTIVE: To investigate the protective mechanism of relaxin against hypoxia-reoxygenation injury of myocardial microvascular endothelial cells. METHODS: Mouse myocardial microvascular endothelial cell line (H5V cells) was used for the experiment. Cells were treated by three different interventions: in control group, cells were normally cultured for 33 hours; in model group, cells were treated by 6-hour hypoxia followed by 3-hour reoxygenation); and in relaxin group, 24 hours of routine culture (180 ng/mL relaxin), 6 hours of hypoxia and 3 hours of reoxygenation (180 ng/mL relaxin) were given to simulate myocardial hypoxia-reperfusion injury. Cell permeability and Caspase-3 activity were then detected. Levels of tumor necrosis factor-α, interleukin-1β and interleukin-6 in cell supernatants were detected by ELISA. Expressions of VE-cadherin, Akt, and GSK-3β at mRNA and protein levels were detected by RT-PCR and western blot, respectively. RESULTS AND CONCLUSION: Compared with the control group, the cell permeability and expression of caspase-3 increased significantly in the model group (P < 0.05). Compared with the model group, the cell permeability and expression of caspase-3 decreased in the relaxin group (P < 0.05). Moreover, the levels of tumor necrosis factor-α, interleukin-1β and interleukin-6 were elevated in the model group, while the levels were significantly decreased after relaxin treatment (all P < 0.05). There were no significantly changes in the mRNA and protein expressions of VE-cadherin, Akt1, and GSK-3β mRNA among three groups (all P > 0.05). Compared with the control group, the expression of phosphorylated VE-cadherin, Akt1 and GSK-3β were decreased in the model group (P < 0.05), and relaxin treatment reversed these changes to the control levels (P < 0.05). To conclude, relaxin treatment could enhance VE-cadherin expression, reduce hypoxiareoxygenation-induced microvascular endothelial cell damage, inhibit inflammatory cytokine release, and reduce cell apoptosis, which may be related to the activation of the Akt/GSK-3β signaling pathway. © 2023, Publishing House of Chinese Journal of Tissue Engineering Research. All rights reserved.     

阿尔茨海默病中Aβ损伤线粒体的研究进展

The β-amyloid protein (Aβ) has long been considered to associate with Alzheimers disease (AD). In addition, groups of evidence show that the soluble intracellular Aβ plays an important role in the disease development. The mitochondrial dysfunction induced by Aβ accumulation is a main pathologic process in early stage of AD. Matured Aβ is imported into the mitochondria through an unclear route. Once inside the mitochondria, Aβ is able to interact with a number of targets, including amyloid-binding alcohol dehydrogenase (ABAD) and cyclophilin D (CypD), which is a component of the mitochondrial permeability transition pore. Interference with the normal functions of these proteins results in mitochondrial injury, such as energy dyshomeostasis, production of reactive oxygen species, membrane permeability alteration and so on. This review explores the Aβ generation and location in mitochondria. The mitochondrial injury induced by the interaction between Aβ and its targets are also discussed.     

Effects of antioxidant and NF-κB on the induction of iNOS gene in rat pulmonary microvascular endothelial cells in vitro

Effects of antioxidant and NF-κB on the induction of iNOS gene in rat pulmonary microvascular endothelial cells in vitro     

Effect of blood viscosity on computational fluid dynamics in vascular network北大核心

BACKGROUND: Patients with osteoporosis patients often present with increased blood viscosity, which belongs to the category of “blood stasis” in traditional Chinese medicine. How, the effects of increased blood viscosity on microvascular fluid properties remain to be elucidated. OBJECTIVE: To investigate the effect of blood viscosity on the hydrodynamics of vascular network by computational fluid dynamics. METHODS: The three-dimensional model of vascular network was constructed based on the Geometry module of ANSYS 19.0 software, and the vascular network was then meshed to tetrahedral elements in Mesh module. The vascular network was assumed to rigid wall without slip, and the blood was assumed to laminar, viscous, and incompressible Newtonian fluid. Blood density, velocity, and a series of blood viscosity coefficients were also established. The Navier-Stokes equation was adopted for simulation. The effects of blood viscosity on the hydrodynamics of different parts of vascular network were analyzed. RESULTS AND CONCLUSION: The streamline, velocity, mass flow, and wall shear stress in the vascular network demonstrated a “U” shaped distribution, that is, these contents in outlet and inlet were higher than those in the junction of the vascular network. With the increase of blood viscosity, the streamline, velocity, and mass flow in each part of vascular network became sparse and decreased slightly; however, the wall shear stress increased significantly. The largest percentage change in wall shear stress was observed at the intersection of vascular network. To conclude, blood viscosity will change the hydrodynamics of the vascular network, especially in term of wall shear stress. Computational fluid dynamics can provide a good insight into the influence of blood viscosity alteration on the hydrodynamic performance of the blood, thereby providing a new research tool for the study of osteoporosis based on the coupling of angiogenesis and osteogenesis by tonifying the kidney and activating the blood circulation. © 2023, Publishing House of Chinese Journal of Tissue Engineering Research. All rights reserved.     

细胞胀亡的研究进展

Oncosis is a special kind of non-apoptotic cell death mode. It is characterized by cellular swelling, organelle swelling, blebbingand increased membrane permeability. More and more attentions pay to the research of this field in recent years. The review discuss the recent advances of oncosis on pathological change, molecular mechanisms and detection approaches．     

A Mathematical Model of Renal Blood Distribution Coupling TGF, MR and Tubular System

Objective：To investigate the relationship between renal blood distribution and the physiological activities of the kidney. Methods：A mathematical model is developed based on response （MR） Hagan-Poiseuille law and mass transport, coupling mechanics of myogenic tubuloglomerular feedback （TGF） and the tubular system in the renal medulla. The model parameters, including the permeability coefficients, the vascular lumen radius and the solute concentration at the inlet of the tubes, are derived from the experimental results. Simulations of the blood and water flow in the loop of Henel, the collecting duct and vas rectum, are carried out by the model of the tubular system in the renal medulla, based on conservations of water and solutes for transmural transport. Then the tubular model is coupled with MR and TGF mechanics. Results：The results predict the dynamics of renal autoregulation on its blood pressure and flow, and the distributions are 88.5% in the cortex, 10.3% in the medulla, and 1.2% at papilla,respectively. The fluid flow and solute concentrations along the tubules and vasa recta are obtained. Conclusion ：The present model could assess renal functions qualitatively and quantitatively and provide a methodological approach for clinical research.     

IL-6-deficient Mice Are Susceptible to Ethanol-induced Hepatic Steatosis： IL-6 Protects against Ethanol-induced Oxidative Stress and Mitochondrial Permeability Transition in the Liver

Interleukin-6 (IL-6)-deficient mice are prone to ethanol-induced apoptosis and steatosis in the liver; however,the underlying mechanism is not fully understood. Mitochondrial dysfunction caused by oxidative stress is an early event that plays an important role in the pathogenesis of alcoholic liver disease. Therefore, we hypothesize that the protective role of IL-6 in ethanol-induced liver injury is mediated via suppression of ethanol-induced oxidative stress and mitochondrial dysfunction. To test this hypothesis, we examined the effects of IL-6 on ethanol-induced oxidative stress, mitochondrial injury, and energy depletion in the livers of IL-6 (-/-) mice and hepatocytes from ethanol-fed rats. Ethanol consumption leads to stronger induction of malondialdehyde (MDA) in IL-6 (-/-) mice compared to wild-type control mice, which can be corrected by administration of IL-6. In vitro,IL-6 treatment prevents ethanol-mediated induction of reactive oxygen species (ROS), MDA, mitochondrial permeability transition (MPT), and ethanol-mediated depletion of adenosine triphosphate (ATP) in hepatocytes from ethanol-fed rats. Administration of IL-6 in vivo also reverses ethanol-induced MDA and ATP depletion in hepatocytes. Finally, IL-6 treatment induces metallothionein protein expression, but not superoxide dismutase and glutathione peroxidase in cultured hepatocytes. In conclusion, IL-6 protects against ethanol-induced oxidative stress and mitochondrial dysfunction in hepatocytes v/a induction of metallothionein protein expression, which mav account for the nrotective role of IL-6 in alcoholic liver disease.     

Microvascular permeability.

This review addresses classical questions concerning microvascular permeabiltiy in the light of recent experimental work on intact microvascular beds, single perfused microvessels, and endothelial cell cultures. Analyses, based on ultrastructural data from serial sections of the clefts between the endothelial cells of microvessels with continuous walls, conform to the hypothesis that different permeabilities to water and small hydrophilic solutes in microvessels of different tissues can be accounted for by tortuous three-dimensional pathways that pass through breaks in the junctional strands. A fiber matrix ultrafilter at the luminal entrance to the clefts is essential if microvascular walls are to retain their low permeability to macromolecules. Quantitative estimates of exchange through the channels in the endothelial cell membranes suggest that these contribute little to the permeability of most but not all microvessels. The arguments against the convective transport of macromolecules through porous pathways and for the passage of macromolecules by transcytosis via mechanisms linked to the integrity of endothelial vesicles are evaluated. Finally, intracellular signaling mechanisms implicated in transient increases in venular microvessel permeability such as occur in acute inflammation are reviewed in relation to studies of the molecular mechanisms involved in signal transduction in cultured endothelial cells.     

Critical role of microvasculature basal lamina in ischemic brain injury

Cerebral vascular system can be divided into two categories: the macrovessels and microvessels. The microvessels consist of arterioles, capillaries and venules. There are three basic components in the microvasculature: endothelial cells, basal lamina and end-feet of astrocytes. The basal lamina is situated between the endothelial cells and the end-feet of astrocytes, and connects these two layers together. Damage to the basal lamina causes the dismantlement of microvascular wall structures, which in turn results in increase of microvascular permeability, hemorrhagic transformation, brain edema and compromise of the microcirculation. The present article reviews microvascular changes during ischemic brain injury, with emphasis on basal lamina damage.     

64例Ⅱ例糖尿病患者的甲襞微循环改变和加权积分值分析

本文对64例Ⅱ型糖尿病患者和60例正常人进行了甲襞微循环观察。结果提示:Ⅱ型糖尿病患者甲襞微循环在形态、流态,袢周均较正常人有明显异常。并试述应用SWC—ⅡB型微循环参数测量仪和田牛氏甲襞微循环加权积分表的初步体会。     

Endothelial glycocalyx dysfunction in disease: albuminuria and increased microvascular permeability

Appreciation of the glomerular microcirculation as a specialized microcirculatory bed, rather than as an entirely separate entity, affords important insights into both glomerular and systemic microvascular pathophysiology. In this review we compare regulation of permeability in systemic and glomerular microcirculations, focusing particularly on the role of the endothelial glycocalyx, and consider the implications for disease processes. The luminal surface of vascular endothelium throughout the body is covered with endothelial glycocalyx, comprising surface-anchored proteoglycans, supplemented with adsorbed soluble proteoglycans, glycosaminoglycans and plasma constituents. In both continuous and fenestrated microvessels, this endothelial glycocalyx provides resistance to the transcapillary escape of water and macromolecules, acting as an integral component of the multilayered barrier provided by the walls of these microvessels (ie acting in concert with clefts or fenestrae across endothelial cell layers, basement membranes and pericytes). Dysfunction of any of these capillary wall components, including the endothelial glycocalyx, can disrupt normal microvascular permeability. Because of its ubiquitous nature, damage to the endothelial glycocalyx alters the permeability of multiple capillary beds: in the glomerulus this is clinically apparent as albuminuria. Generalized damage to the endothelial glycocalyx can therefore manifest as both albuminuria and increased systemic microvascular permeability. This triad of altered endothelial glycocalyx, albuminuria and increased systemic microvascular permeability occurs in a number of important diseases, such as diabetes, with accumulating evidence for a similar phenomenon in ischaemia-reperfusion injury and infectious disease. The detection of albuminuria therefore has implications for the function of the microcirculation as a whole. The importance of the endothelial glycocalyx for other aspects of vascular function/dysfunction, such as mechanotransduction, leukocyte-endothelial interactions and the development of atherosclerosis, indicate that alterations in the endothelial glycocalyx may also be playing a role in the dysfunction of other organs observed in these disease states.     

Vasomotion model explanation for urea rebound

Urea rebound after hemodialysis is generally attributed to urea entering the circulation from poorly perfused tissue and/or entering from regions with low membrane permeability for urea. Another explanation for rebound is based on disorders in the microcirculation, connected with the phenomenon of vasomotion, i.e., cyclic opening and closing of microvessels. The purpose of the following mathematical model is to explain observed urea rebound by the vasomotion phenomenon. The significance of vasomotion is related to the fact that a significant fraction, up to 80-95%, of all microvessels are closed while others are being perfused. The rate with which open microvessels "migrate" through the tissue determines quality of perfusion. A stochastic scheme for describing vasomotion is developed. Probabilities to change the state of microvessels are defined as follows: alpha = probability to be open and remain open; beta = to be open and become closed; v = to be closed and remain closed; mu = to be closed and become open. The activity of vasomotion is defined by the rate of vasomotion, R, R = beta + mu, and can be measured using a curve of urea concentration.     

Effects of Stimulation of the Trigeminal Caudal Nucleus on Microvascular Permeability in the Eye in Normal and Capsaicin-Treated Rats

Electrical stimulation of the trigeminal caudal nucleus in rats evoked increases in the permeability of eye microvessels. The microvascular effect did not appear when the nucleus was stimulated after administration of capsaicin 10 days before surgery (total dose 150 mg/kg, s.c., on two sequential days, given as 20, 30, 50, and 50 mg/kg). It is suggested that capsaicin-sensitive neurons in the trigeminal ganglion mediate the microvascular effect of stimulation of the trigeminal caudal nucleus.     

Effect of histamine on microvascular permeability in the rat stomach

The effect of histamine on gastric microvascular permeability to macromolecules in the rat was studied using fluorescent in vivo microscopy. Histamine was applied topically to the serosal surface for study of the muscularis externa, to the submucosa, and to the superficial mucosa, and the area of leaks of a fluorescein-albumin conjugate from microvessels was quantitated. In the muscularis externa both histamine and an H1-agonist, but not an H2-agonist, caused dose-dependent leak of conjugate from venules. An H1-antagonist, but not an H2-antagonist, decreased the histamine-induced leak. In the submucosa histamine caused dose-dependent dilatation of arterioles but not leak of conjugate. In contrast, bradykinin caused both dose-dependent dilatation of arterioles and leak of conjugate from venules. In the superficial mucosa histamine did not cause any leak. In conclusion, topical histamine 1) increased microvascular permeability to macromolecules from venules in the muscularis externa via H1-receptors, 2) did not affect microvascular permeability in the submucosa (this may be due to lack of histamine receptors on the venules as bradykinin increased venular permeability), and 3) did not affect microvascular permeability in the superficial mucosa, but there might not have been adequate histamine backdiffusion.     

1-磷酸鞘氨醇对血小板活化因子所致大鼠肠系膜微血管通透性增高的影响

目的:探讨1-磷酸鞘氨醇(S1P)对血小板活化因子(PAF)引起的大鼠肠系膜微血管通透性增高的影响。方法:本研究拟采用大鼠在体肠系膜微血管灌注的方法,通过测定微静脉的静水传导性(Lp),观察S1P对外源性PAF引起的微血管通透性增高的影响;并利用激光共聚焦显微镜技术,观察S1P对PAF引起的微血管荧光强度变化以及血管内皮细胞钙粘蛋白(VE-cadherin)变化的影响。结果:给予10nmol/LPAF作用后,大鼠肠系膜微血管Lp值明显增高,而经1μmol/L S1P预处理后,再给予PAF并未引起Lp的明显变化;PAF作用微血管后可见微血管内皮细胞间隙打开,微血管荧光强度明显增加,大量红色荧光微球(FMs)分布于内皮细胞间隙之中,S1P预处理后并未见内皮细胞间隙打开及FMs的明显积聚,微血管荧光强度与正常对照值比较无显著差异。结论:PAF可增加微血管的通透性,改变内皮细胞VE-cadherin正常结构,导致粘附连接断裂,细胞间隙形成,血管通透性增加可能与此结构变化有关。S1P能改善PAF引起的血管通透性增高,其作用与加强内皮细胞间粘附连接,抑制细胞间隙打开有关。     

SD大鼠眶下神经微血管的结构特点*

目的： 通过去除和不去除眶下神经外膜焦点堆迭的对比及H-E 染色,研究大鼠眶下神经微血管解剖结构 特点。方法： 10%水合氯醛腹腔内注射麻醉大鼠,开胸插管后依次用0.9% 氯化钠和4%多聚甲醛灌流,再用 37℃ 5%明胶- 墨汁混合液灌注,解剖游离眶下神经,将去除和未去除神经外膜的眶下神经制成透明标本后获取 不同焦距层面照片进行焦点堆迭,石蜡包埋后,切片行H-E 染色,观察大鼠眶下神经微血管的分支、分布及走行 特点。结果：大鼠眶下神经外膜染色呈大片区域的深染,近心端染色更深。去除神经外膜的眶下神经微血管清晰 度高。眶下神经微血管的数量众多、密度大、染色深,近心端管径较大,微血管在不同层面发出的分支吻合形成 微血管网。在神经纤维之间分布较多管径较小的微血管,多沿神经纤维纵向迂曲走行,在走行过程中可斜向或纵 向发出分支吻合成网。结论： SD 大鼠眶下神经微血管数量多、密度大,在迂曲走行过程中发出分支并吻合成网状。     

Effects of isoprenaline and cooling on histamine induced changes of capillary permeability in the rat hindquarter vascular bed

Histamine infused intra-arterially into artificially perfused, maximally dilated rat hindquarters markedly increased fluid filtration and CFC but had essentially no effect on the diffusion capacity to small molecules. Isoprenaline largely prevented the increase in fluid filtration and CFC if infused prior to the start of the histamine infusion and, if infused after the start of the histamine infusion, promptly reduced fluid filtration and CFC to near control levels. Additionally, it was noted that severe cooling of the perfusate also largely prevented the marked increase in fluid filtration and CFC by histamine. This antagonism of histamine induced increases in macromolecular permeability represents a direct action of isoprenaline on the microvascular membrane which effectively counteracts that of histamine. The data also suggest that the large pores created by histamine are different from the large pore through which macromolecules normally transverse the microvascular membrane, and that catecholamines may exert a regulatory function in the control of microvascular permeability to macromolecules in pathophysiological states associated with massive histamine release.