The flow distribution of leukocytes in the microvasculature of rat skeletal muscle during hemorrhagic shock was measured by Microcirculation Image Multiple Parameters Computer Analysis System (MIMPCAS). It was found that the change of leukocyte flow distribution had taken place in V3 during hemorrhagic shock as follows: central axial-flowing leukocytes moved slowly, marginated to the vessel wall then started to roll along the wall, and stuck to the endothelium at last. During transfusion blood flow became faster, sticking leukocytes were rushed out to be rolling along the vessel wall and accelerated to enter the central stream. Total leukocyte -endothelium contact time (TLECT), which is a quantitative index for leukocyte endothelium interaction, is calculated, and it was found that TLECT was prolonged in shock state. The results show that it is not enough to increase blood pressure and shear stress to liberate sticking leukocytes, and it is necessary to search for a new approach to decrease the adhesive force between leukocyte and endothelium. Polygonum cuspidatum may not only increase wall shear rate but also decrease the adhesive force.

Theincreasedmicrovascularpermeabilityappearsmainlyinvenuleduringinflammation , shock ,andburns .Endothelialcellsplayanimportantroleinvenulepermeabilityenhancement.Therearetwo kindsofpathwayformacromoleculeextravasation .Oneisparacellularpathwayandanotheristranscellular pathway ,whicharerelatedtotheformationofendothelialgaportranscellularopeningsseperately .Thealter ationofintercellularrelatedprotein ,suchasoccludin ,claudin ,zonaoccludens (ZO) ,junctionaladhesion molecule (JAM) ,VE -cadherin ,catenin ,integrin ,etc ,andthealterationofendothelialcytoskeleton ,such asrearrangementofactinfilament,formationofstressfiberandfocaladhesion ,etc ,involveinthepathogenesis ofincreasedmicrovascularpermeability . [

Endogenous carbon monoxide (CO) is proposed to be an intracellular signaling molecule. As a new gaseous messenger, CO shares with nitric oxide (NO) the ability of modulating neuroendocrine function and inducing vasorelaxation, mainly by stimulating soluble guanylate cyclase and regulating the level of cGMP. This review emphasized the endogenous source of CO and the interaction of CO- and NO-generating systems. It also discussed the biological effects of CO and the underlying mechanisms.

Vascular hyperpermeability is a cardinal feature of inflammation or burn in which an array of inflammatory mediators can cause such changes in the microvessels. The functional measures of microvascular exchange that represent the properties of microvascular walls are the permeability coefficients which have been reported from measurements on intact whole organisms (including human subjects), on perfused tissues and organs, on single perfused microvessels, and on monolayers of cultured microvascular endothelial cells. In this review, we summarize some experiments of vascular permeability in individually isolated perfused microvessels. [

Objective To determine the effects of two fluid resuscitation strategies on the changes of hemodynamic variables,serum concentration of tumor necrosis factor-alpha(TNF-α)and interleukin-6 (IL-6)in a clinically relevant model of uncontrolled hemorrhagic shock in pregnant rabbits.Methods Hemorrhagic shock was induced by bleeding via carotied artery,followed by transection of a medium vessel in gestational sac.Experimental design consisted of three phases,shock phase(0-30 min),prehospital phase(30-90 min)and hospital phase(90-180 min).Twenty pregnant rabbits were randomly divided into two groups(n=10/group),aggressive fluid resuscitation group(PNL group)and limited volume resuscitation group(PLH group).In the shock phase,animals were hemorrhaged by blood withdrawal to mean arterial pressure(MAP)of 40-45 mm Hg(1 mm Hg=0.133 kPa)via carotid artery.In the prehospital phase,a medium vessel in the gestational sac was transected,then the animals in the PNL group and PLH group were resuscitated with 0.9% normal saline(NS)and shed blood to MAP of 80,60 mm Hg respectively.In the hospital phase,bleeding was controlled by surgical intervention and all the animals were reinfused with shed blood and NS to MAP 80 mm Hg.Hemodvnamic variables and respiration rate were monitored and blood samples were collected for TNF-α and IL-6 measurement.and finally subsequent volume resuscitation and survival rate were recorded.Results (1)At 120 min,the respiration rate and heart rate in the animals assigned to PLH group was(66±16)bpm,(235±41)bpm respectively,which were significantly lower than those in PNL group(P＜0.01),while MAP and central venous pressure in the PLH group was(80.4±7.2)mm Hg,(8.0±4.4)cm H2O,respectively,which were significantly higher than those in PNL group(P＜0.01);(2)The serum concentration of TNF-α,IL-6 of all the animals were markedly increased after hemorrhagic shock.and peak at 24 min.The serum concentration of TNF-α,IL-6 in animals assigned to PLH group were(105±67)ng/L,(118±51)ng/L respectively,which were significantly lower than those in PNL group(P＜0.01).The serum concentration of TNF-α,IL-6 in the animals assigned to PLH group were decreased to normal at 480 min;(3)The subsequent blood transfusion volume and NS resuscitation volume in PLH group in prehospital phase were(16.0±2.2)ml,(39.0±5.5)ml respectively,while those in hospital phase were(28.0±6.7)ml,(90.0±7.1)ml respectively,which were significantly lower than those in PNL group(P＜0.05);(4)The 24 and 72 hours survival rate in the animals assigned to PLH group were 100%,90% respectively;which were significantly higher than those in PNL group(P＜0.01).Conclusion Limited volume resuscitation improves thermodynamic changes of pregnant rabbit,attenuates the increase of serum concentration of TNF-α,IL-6,and results in higher survival rate.Limited volume resuscitation is an ideal means for hemorrhagic shock resuscitation in pregnant rabbit.

NF-?B is thought of as a genetic switch to control expressions of many target genes and directly participates in pathogenesis of infection, inflammation, stress, immunoresponse, cellular apoptosis, toxic shock and tumor as well as cell-cycle regulation and cell differentiation. The overactivation of NF-?B is intimately involved in many human diseases. Various therapeutic strategies against NF-?B, to date, include anti-inflammatory drugs, antioxidants, immunosuppressive agents, inhibitors of protease and proteasome, prostaglandings, nitric oxide, IL-10, microbial products, synthetic inhibitors, antisense oligonucleotides and decoy deoxyoligonucleotides. Studies are underway to develop NF-?B member-specific and cell type-specific drugs that can inhibit the activation of NF-?B only in target cells and that may become a novel way to treat the human diseases.

AIM: To investigate whether small GTPase RhoA's downstream effector Rho kinase mediates burn serum-induced endothelial hyperpermeability. METHODS: Primary cultured rat dermal microvascular endothelial cells (DMECs) were exposed to serum isolated from burned or sham burn rats for 6 hours and 8 hours, respectively, and did or didn't pretreated or post-treated with Y-27632 (30 ?mol/L), a specific inhibitor of Rho kinase. ECs were then prepared for routine scanning electron microscopy observation, or stained with rhodamine-phalloidin for F-actin visualization. Permeability to FITC-albumin was evaluated using EC monolayers. RESULTS: Stimulation with 15% burn serum for 6 h changed the ultrastructure on cellular surface of DMECs with appearance of ripple marks instead of microvillus. The small protuberances at cellular lateral were shorten and the gaps were seen between adjacent cells. Post-treatment of Y-27632 reversed the changes of ultrastructure on the cellular surface. Burn serum induced a striking reorganization of actin cytoskeleton with a weakening of fluorescent intensity of the peripheral filament bands and formation of the long and thick stress fibers, lamellipodia and filopodia. The stress fibers were diminished by pretreatment or post-treatment of Y-27632. But lamellipodia and filopodia were not influenced by pretreatment or post-treatment of Y-27632. Pre-treatment of Y-27632 also attenuated significantly the increase in EC monolayer permeability stimulated by burn serum for 6 h. However, post-treatment of Y-27632 could not attenuated burn serum-induced endothelial hyperpermeability response although their Pa values were lower than simple burn serum group's. CONCLUSION: These findings indicate that Rho kinase is involved in the mediation of burn serum-induced endothelial actin cytoskeleton reorganization and early stage of barrier dysfunction. [

AIM: To study the effect of microelement powder (MP) on membrane potential of vascular endothelial and smooth muscle cells of rats in order to elucidate the mechanism of microcirculation improvement by MP. METHODS: Cultured pulmonary vascular endothelial cells (EC) and aortic smooth muscle cells (SMC) of rats and detecting the changes of cellular membrane potentials by using potential-sensitive fluorescent probe and laser jet confocal microscope. RESULTS: MP hyperpolarized SMCs significantly. Glybenclamide (2 μmol/L), a blocker of KATP channel, which had no effect on membrane potential of SMCs, reversed the hyperpolarization of MP completely; MP hyperpolarized ECs slightly, but the effect was unaffected by glybenclamide. CONCLUSION: MP hyperpolarizes SMCs by activating KATP channels and leads to dilation of microvessels and improvement of microcirculation.

BACKGROUND:Basic fibroblast growth factor(bFGF)can promote production of collagen,fibronectin and matrix enzyme in healing wounds.However,dysregulation of this process,such as the abnormal coordination of cell proliferation,extracellular.matrix and neovasculadzation formation,or remodeling of the wound matrix will lead to excess accumulation of scar tissues.OBJECTIVE:To investigate effects of bFGF on normal skin wound healing and hypertrophic scar formation.METHODS:Normal and hypertrophic scar fibroblasts from tissue biopsies from 5 patients who underwent plastic surgery for repairing hypertrophic scars were isolated and cultured.The expressions of collagen,fibronectin and protein synthesis were detected by RT-PCR and ELISA.The mitochonddal membrane potential changes were measured using JC-1 staining and flow cytometry.Simultaneously,adenosine tdphosphate(ATP)levels were determined by chemiluminescence method.The effects of bFGF on these indexes of normal and hypertrophic scar fibroblasts were observed.RESULTS AND CONCLUSION:Hypertrophic scar fibroblasts become slower after being exposed to bFGF,which selectively inhibited type Ⅰ collagen production in hypertrophic scar fibroblasts(P<0.05).Although bFGF inhibited type]collagen production,it had no effect on type Ⅲ collagen expression in both normal and hypertrophic scar fibroblasts.However,fibronectin expression in the normal fibroblasts was up-reguleted after bFGF treatment(P<0.05).In addition,the mitochonddal membrane potential tended to depolarization,although no statistical difference,in hypertrophic scar fibroblasts treated with bFGF(10 or 100 μg/L).bFGF treatment increased the cellular ATP levels in the normal fibroblasts,while there were no significant alterations in the hypertrophic scar fibroblasts over a treatment of bFGF(10 or 100 μg/L,P<0.05).The results suggest that there are differential effects and mechanisms on the skin fibroblasts with bFGF treatment in normal wound healing and hypertrophic scar formation.

Objective To investigate relationship between the variation degree of platelet mitochondria in rats with severe hemorrhagic shock and the degree of shock.Methods Thirty-six Wistar rats were divided into sham group,shock 30,60,and 120 minutes groups,shock 120 minutes + normal saline (NS) + blood reinfusion group (NS group) and shock 120 minutes + polydatin (PD) + blood reinfusion group (PD group) according to random number table,with six rats per group.Content of ATP in platelets was detected by fluorescein-luciferase assay kit; structure of platelet mitochondria by electron microscope; state of mitochondrial permeability transition pore by Calcein-AM and CoCl2 ; change of mitochondrial membrane potential (△Ψm) by JC-1 mitochondrial membrane potential kit; lipid hydroperoxide (LPO) in platelets by LPO assay kit; stability of platelet lysosomes by acridine orange (AO).Results ATP released from platelets was reduced significantly in shock 60 minutes group (P ＜0.01) and with the prolong of shock period,further reduction was observed,particularly in NS group [(50.75 ± 9.15)％ of normal value].Mitochondrial swelling with poorly defined crista structure,declined △Ψ and low lysosome stability (pale cells were increased) were observed in shock 30 minutes group.Calcein fluorescence in mitochondria was faded in shock 60 minutes group (P ＜ 0.01).Whereas in PD group,all the above indices presented some recovery with ATP level returned to nearly (79.57 ± 8.48) ％ of normal value in particular.Conclusions Platelet mitochondrial dysfunction takes place at 30-60 minutes following severe shock.Hence,it may be served as an non-invasive index for the diagnose and treatment of severe shock.