Objective To investigate the changes of plasma adrenomedulin(AM) and nitric oxide(NO) and their correlation in rats with traumatic shock. Methods 40 Sprague-Dawley rats were randomly divided into control group(n=10), traumatic shock without resuscitation group (n=10), traumatic shock with resuscitation group (n=10) and aminoguanidine group (n=10). 10 rats of control group only received intubation after anesthesia. The other 30 rats were made animal models of traumatic shock by crashing both femur shafts and doing bloodletting to mean arterial pressure of 35～45mmHg via femoral artery. Hypotention of rats in traumatic shock with resuscitation group were maintained 30min, and then the lost blood was returned, followed by an infusion of equal volume of Ringer's solutions. Rats of aminoguanidine group were given aminoguanidine 60mg/kg body weight during resuscitation. The changes of Plasma levels of AM and NO in every group of rats were observed before and after shock. Results The plasma level of both AM and NO in the rats of traumatic shock was higher than that in the rats of control group, and reached the highest 30min after resuscitation. The level changes of plasma AM and NO in the rats of aminoguanidine group were not significant. The level change of plasma AM was positive correlation with the level change of plasma NO. Conclusions AM and NO may play an important role in the pathological process of traumatic shock. AM develops its role probably by NO.

Objective To investigate the changes of membrane potential of mesenteric arteriolar smooth muscle cells (ASMCs) and large conductance calcium-activated potassium channel (BK Ca ) following hemorrhagic shock in rats. Methods (1) The Wistar rats were randomly divided into sham and shock groups. The hemorrhagic shock model was duplicated. The sham group was given operation rather than bloodletting. (2) ASMCs were isolated with pronase E and mesenteric arteries A2 and A3 from sham and shock rats also isolated. (3) The changes of membrane potential of ASMCs and potassium channel were recorded using cell-attach and inside-out patch lamps. Results (1) The membrane potential of ASMCs changed from -41 mV to -65 mV two hours after hemorrhagic shock. (2) After shock, the conductance of BK Ca did not change, while the open probability (NPo) of BK Ca was enhanced and the reversal potential of BK Ca changed significantly. Conclusions Membrane hyperpolarization of ASMCs occurs posterior to hemorrhagic shock, the cause for which may be the activation increase of BK Ca .

Objective The objective of this study was to investigate the role of sulindac in sensitization effects of NF-κB on apoptosis induced by TNF-α in human breast cancer.Methods The human breast cancer MCF-7 cell line was added sulindal in the logarithmic growth phase and the final concentrations of sulindac were 0.5 and 1.0 mmol/L.The cells in control group was cultured without adding succinic acid.After sulindac treatment for 48 h,flow cytometry,MTT and Western blotting were used to analyze the effect and mechanism of cell growth in MCF-7 cells.Results The inhibitory rate of cell proliferation was(29.17±1.23)% and(38.15±1.51)% in MCF-7 cells treated with 0.5 and 1.0 mmol/L of Sulindac for 48 h,respectively,when compared to the control group(1.15 ± 0.02)%(P<0.05).Compared with the control group,0.5 and 1.0 mmol/L of sulindac were significantly increased the G0/G1 phase in MCF-7 cells(P<0.05).The apoptosis rate of sulindac in MCF-7 cells was significantly higher than that in the control group(P<0.05).The expression levels of TNF-α were(2.09±0.67)% and(1.18±0.09)% in the concentrations of 0.5 and 1.0mmol/L sulindac,respectively,in MCF-7 cells when compared to the control group(7.42±0.56)%.Conclusion Sulindac has a certain effect on the growth of human breast cancer cells,which can promote the prolongation of cell cycle at the G0/G1 phase and improve sensitization of apoptosis.This mechanism may be related to the inhibition of TNF-α activity.

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.

AIM: To study the effect of cGMP-dependent protein kinase (PKG) on the pathogenesis of burn shock. METHODS: Confluent endothelial cells were disintegrated and centrifugated to obtain cell lysates after being treated with 10% burn serum or PKG activator 8-Br-cGMP. PKG activity of lysates was measured with radioactive isotope label method in a reaction system of phosphorylation of specific substrate H2B by PKG, and the shape and the distribution of intracellular filamentous actin were detected by specific fluorescence staining. For the control study, the PKG specific inhibitor KT5823 were used to pretreat the endothelial cells before the administration of burn serum or PKG activator 8-Br-cGMP. RESULTS: Exposures to burn serum and 8-Br-cGMP led to a rapid time-dependent increase in endothelial PKG activity and the polar distribution of intracellular filamentous actin, and preincubation with KT5823 abolished those effects. CONCLUSIONS: The results suggest that burn serum induces PKG activation and the stress variety of filamentous actin in the vascular endothelial cells, which probably contributes to the endothelial hyperpermeability after burn shock. [

AIM: To study I_ to channel function in severe burn and its contribution to cardiac dysfunction induced by severe burn. METHODS: CHO-K1 cells were transfected with human Kv4.3, the major subunit of human I_ to channel. The expressed Kv4.3 channels were recorded by whole-cell patch clamp and the effects of rat burn serum on Kv4.3 current densities and kinetics were observed. RESULTS: Kv4.3 channels expressed in CHO-K1 cells were endowed with the characterization of fast activation and inactivation, which was quite similar to that of native I_ to channels in cardiomyocytes. Rat's burn serum at the concentration of 2% decreased the current density significantly. At +40 mV, the current density in control group was (67.6?15.1) pA/pF, in contrast to (32.3?9.7)pA/pF in burn serum-treated group (P

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 ?mol/L), a blocker of K ATP 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 K ATP channels and leads to dilation of microvessels and improvement of microcirculation.

Objective To study the role of P38 mitogen-activated protein kinase(P38 MAPK) activation in high level glucose-induced microvascular hyperpermeability.Methods Rats were induced to diabetis by intraperitoneal injection of streptozotocin(STZ).The rats were divided into 5 groups,including normal,diabetes,control,MKK6b(A) and MKK6b(E) groups.The permeability coefficient to albumin(Pa) was measured in venules of in vivo mesenterium using a fluorescence ratio technique;Morphological changes of microvascular endothelial cell were monitored by observing fluorescence of F-actin stained with rhodamine-phalloidin.Results The permeability of diabetic rats was obviously increased.The activation of P38 MAPK by MKK6b(E) could increase microvascular permeability in normal rats,and the inhibition of P38 MAPK by MKK6b(A) could inhibit hyperpermeability of diabetic rats.Conclusion The activation of P38 MAPK induced by hyperglycemia may play a role in diabetic microvascular hyperpermeability.

AIM: To detect the effect of intercellular adhesion molecule-1(ICAM-1) monoclonal antibody on microcirculation disorder in burn shock of Wistar rats. METHODS: The blood flow velocity and diameter of venule were measured with RBC tracking correlator and IV550 model video microscaler in burn shock models of rats. The number of leukocytes adhered on venule wall was calculated under microscope. The animal survival time was observed. RESULTS: ICAM-1monoclonal antibody could attenuate the falling of mean arterial pressure, significantly reduce the number of leukocytes adhered on venule wall, and obviously prolong the animal mean survival time, but less than 24h. CONCLUSION: ICAM-1 monoclonal antibody can decrease the number of adhered leukocytes to endothelial cells, attenuate the tether of leukocytes to venule and improve microcirculation and protect tissue cells in burn shock of rats. However, a comprehensive therapy should be taken in severe shock.

AIM: To elucidate the mechanism of polydatin(PD) in increasing the contractility of myocardial cells by observing the cytosolic free calcium concentration ([Ca 2+ ]i) of myocardial cells of rats. METHODS: The cells were labelled with fluo-3-AM, and [Ca 2+ ]i was determined by use of confocal microscopy (ACAS 570). RESULTS: In the study, we found that [Ca 2+ ]i of myocytes was elevated 10min after adding PD (0.6 mmol/L), but [Ca 2+ ]i of some cells increased to 111.80%?2.22% vs baseline, the others to 224.00%?24.33%. The effect of PD was inhibited remarkably by pretreated with EGTA(2mmol/L), verapamil (50 ?mol/L), a kind of L-calcium channel antagnist, and tetrodotoxin ( 1 ?mol/L), a kind of sodium channel blocker 10 min before PD, the fluorescence value were decreased to 53.00%?9.02% , 52.00%?7.07% and 72.67%?12.70% respectively vs baseline (P