Alteration of transient outward potassium current in ventricular myocytes from 1-week and 2-month infarcted rabbit hearts

AIM: To study the current density of transient outward potassium current (I_to) in cells from the epicardial zone of the 1-week and 2-month infarcted rabbit heart. METHODS: Rabbits were infarcted by ligation of the left anterior descending coronary artery, 1 week as well as 2 months later, the single ventricular myocytes were isolated enzymatically from the infracted area of 1-week infracted rabbit heart (PMI-1 week) and 2-month infracted heart (PMI-2 months), region remote from the infracted zone of 2-month infracted heart (REM-2 months) and free wall of left ventricule from noninfarcted heart (CON). I_to was recorded using whole cell patch-clamp techniques. RESULTS: Membrane capacitance of myocytes in REM-2 months group was signifitantly larger than that in CON. I_tocurrent density (at +60 mV) was significantly reduced in PMI-1 week and PMI-2 months compared with CON , P＜0.01. Nevertheless, there was an significant increase in PMI-2M compared with PMI-1W, P＜0.05. I_to current density was also significantly decreased in REM-2 months compared with CON (P＜0.05), while there was an significant increase in REM-2 months compared with PMI-2 months, P＜0.05. CONCLUSION: The results indicated that the reduction and change of I_to in infarcted rabbit heart were heterogenous. These changes may underlie the abnormally long transmembrane action potentials of these arrhymogenic surviving ventricular fibers of the infarcted heart, thus contributing to reentrant arrhythmias in the infarcted heart. By 2 months after myocardial infarction, the depressed I_to of infracted area had returned to nearly normal, suggesting the presence of reverse remodeling.     

Effects of stretch on transient outward potassium and inward rectifier potassium current in cultured neonatal rat atrial myocytes

AIM：To investigate the effects of mechanical stretch on transient outward potassium current (Ito), inward rectifier potassium current (IK1) and action potential duration(APD) of cultured neonatal rat atrial myocytes. METHODS：Neonatal rat atrial myocytes were isolated and cultured on silicone sheeting with or without stretch for 24 h. The silicone membrane area was increased by 12% in stretched group. The cells without stretch served as control. Ito, IK1 and APD were recorded by the technique of whole-cell patch clamp. RESULTS：Compared with control group, Ito density in stretched myocytes was significantly reduced ［(16±04) pA/pF vs (121±29) pA/pF, P<001］, whereas IK1 density was increased ［(-108±08) pA/pF vs (-88±09) pA/pF, P<001］. The APDs at 50% and 90% levels of repolarization (APD50 and APD90) in the stretched cells were obviously decreased than those in non-stretched cells ［(105±14) ms vs (155±24) ms, (300±28) ms vs (563±36) ms, P<001］. CONCLUSION：Stretch stimulation leads to the reduction of Ito density, the increase in IK1 density and the shortness of APD in cultured rat atrial neonatal myocytes, which may contribute to atrial electrical remodeling induced by pressure overload.     

Blunted response of L-type calcium current to simulated ischemia and reperfusion in ventricular myocytes from diabetic rabbits

AIM: To evaluate the effects of simulated acute ischemia and reperfusion on L-type calcium current (I_{Ca, L}) in ventricular myocytes from diabetic and non-diabetic rabbits.METHODS: Using whole-cell patch clamp techniques, I_{Ca, L} was measured in left ventricular myocytes isolated from 6-week alloxan-induced diabetic rabbits and age-matched control ones at baseline, 5 min of simulated ischemia, and 5 min of reperfusion.RESULTS: There were no significant differences on baseline maximum I_{Ca, L} densities between diabetic and control ventricular myocytes. In control cells (n=11), maximal I_{Ca, L} densities of baseline, ischemia and reperfusion were (-8.36±1.63)pA/pF, (-5.90±1.75)pA/pF and (-4.22±1.02)pA/pF, respectively. The I_{Ca, L} of ischemia was less than that of baseline (P<0.01), while the I_{Ca, L} of reperfusion was less than those of baseline (P<0.01) and ischemia (P<0.05). In diabetic cells (n=9), the I_{Ca, L} of baseline, ischemia and reperfusion were (-7.55±1.62)pA/pF, (-6.05±1.58)pA/pF and (-5.12±1.13)pA/pF, respectively. Only I_{Ca, L} of reperfusion was less than that of baseline (P<0.01), while I_{Ca, L} of ischemia was not significantly different from that of baseline (P>0.05) or reperfusion (P>0.05).CONCLUSION: I_{Ca, L} in diabetic ventricular myocytes represents blunted response to acute ischemic injury, being decreased more slowly than that in control cells. Post-ischemic reperfusion is still a potent inhibitor against I_{Ca, L} in both diabetic and non-diabetic cells. This study may be indicative of the mechanism about ischemia-reperfusion injury to diabetic myocardium and the therapy for diabetic patients with ischemic heart disease.     

Electrical heterogeneity of transient outward current in thyroxine induced ventricular myocytes of cardiomyopathy rat

AIM: To study the electrical heterogeneity of transient outward potassium current (Ito) in left and right ventricular myocytes of cardiomyopathy rat. METHODS: The rats were peritoneally injected with L-thyroxine 0.5 mg/kg for 10 d to establish the model of ventricular hypertrophy. The right and left ventricular parts of the heart were separated and the ventricular myocytes were prepared by step digestion using enzyme solution. Ito was recorded by using whole cell patch clamp technique. The change of the electrical heterogeneity was determined. RESULTS: The electrical heterogeneity of Ito existed in the normal myocytes of left and right ventricles. In the myocytes of left and right ventricles isolated from the cardiomyopathy rats, the electrical heterogeneity was enhanced obviously and showed statistical difference. At +40 mV depolarizing test potential, the current density of Ito in the myocytes of right ventricle was increased from (9.23±0.84) pA/pF to (11.19±1.73) pA/pF, while the current density of Ito in the myocytes of left ventricle was decreased from (6.99±1.14) pA/pF to (4.95 ±1.84) pA/pF and the dispersion was increased. The V1/2 of right ventricle steady inactivation was increased significantly ［from (-68.85±1.37) mV to (-49.86±0.69) mV］. The time constant τ of de-inactivation changed significantly ［τleft=(79.16±7.04) ms,τright=(53.19±3.72) ms］. CONCLUSION: Enhanced electrical heterogeneity of Ito in the left and right ventricular myocytes of cardiomyopathy rat may represent one of the important ionic mechanisms for some arrhythmia caused by myocardial hypertrophy.     

Effect of phosphocreatine on transient outward potassium current in ischemic ventricular mid-myocardial cells of rats

AIM: To determine the effect of exogenous phosphocreatine (PCr) at different concentrations on transient outward potassium (I_to) current in rat ischemic ventricular mid-myocardial (M) cells and to explore the antiarrhythmia mechanism in the treatment of ischemic heart disease. METHODS: M cells were isolated enzymatically from left ventricular mid-myocardium of rats. Peak I_to current was recorded by patch-clamp technique in the whole-cell configuration when M cells were superfused with normal Tyrode solution, simple ischemic solution,and simulated ischemic solution containing PCr at concentrations of 5, 10, 20 and 30 mmol/L for 10 min. RESULTS: Peak I_to current density of M cells superfused with simple simulated ischemic solution was significantly reduced by (76.1?6.3)% (P<0.05) compared with M cells superfused with Tyrode solution. Ischemic solution containing 5, 10, 20 and 30 mmol/L PCr reduced peak I_to current density by (57.1?9.6)% (P<0.05), (40.3?10.3)% (P<0.05), (34.3?9.6)% (P<0.05) and (32.1?10.6)% (P<0.05),respectively. There was statistical difference among ischemic solution without PCr and containing PCr at concentrations of 5 and 10 mmol/L groups (P<0.05). No statistical difference among groups of 10, 20 and 30 mmol/L PCr was observed (P>0.05). CONCLUSION: PCr reverses the inhibition of I_to current under ischemic condition in M cells, which may be the mechanism responsible for arrhythmia prevention in ischemic heart disease. PCr at concentrations of 0~10 mmol/L exerts significant dose-effect relationship.     

Characteristics of transient outward potassium current in repolarization 1 phase from the canine right ventricular mid-myocardial cells

AIM: To examine the electrophysiological characteristics of transient outward potassium current(Ito₁) in repolarization 1 phase from the canine right ventricular M cells. METHODS: By use of whole cell patch-clamp technique, we quantitatively researched the ionic intensity, density of Ito₁ and the notch magnitude of action potential in repolarization 1 phase. RESULTS: (1) The activating process of Ito₁ of canine right ventricular M cells presented evident voltage-dependency. Under the condition of 37℃, 5 000 ms, 0 mV and +70 mV, the average peak Ito₁ intensity of right ventricular M cell were (690±380) pA and (3 130±1 910) pA, respectively (P＜0.01). (2) The Ito₁ intensity of canine right ventricular M cell possessed obvious frequent dependency. Under the condition of 37℃,+70 mV, 500 ms and 5 000 ms, the average peak Ito₁ intensity were (1 690±830) pA,(3 130±1 910) pA, respectively(P＜0.01), corresponding to the increase of action potential "spike-dome" magnitude in repolarization 1 phase. CONCLUSION: Potent Ito₁ as well as the "spike-dome"-like action potential figure mediated by Ito₁ is one of the prominent electrophysiological characteristics of the canine right ventricular M cells.     

Effects of cardiomyopeptidin on sodium current in ventricular myocytes of guinea pigs

AIM: To determine the effect of cardiomyopeptidin on sodium current (I_Na) in ventricular myocytes of guinea pigs and to explore the mechanism of cardiomyopeptidin action at the ionic channel level. METHODS: Single ventricular myocytes of guinea pigs were obtained by enzymatic dissociation method. The whole-cell patch-clamp recording technique was used to record the change of I_Na. RESULTS: Cardiomyopeptidin (1, 5, 10, 50, 100 and 500 mg/L) decreased I_Na in a dose-dependent manner. The inhibition rates were (0±1)%, (6±2)%, (10±2)%, (15±1)%, (22±9)% and (30±6)%, respectively. The time to peak (TTP) was delayed from (2.8±0.7) ms to (3.0±0.8) ms (P<0.05) by cardiomyopeptidin (50 mg/L). In the presence of cardiomyopeptidin (50 mg/L), the current density-voltage curve of I_Na was shifted and without change of its active potential, peak potential, reversal potential, and the shape of the curve. The steady activation curve, the steady inactivation curve and the steady inactivation recovery curve of I_Na were not affected. CONCLUSION: Cardiomyopeptidin inhibits the I_Na in guinea pig ventricular myocytes, which may be one of the mechanisms of its antiarrhythmic effect.     

Effects of piperine on abnormalities of inward rectifier potassium current and ultra rapid delayed rectifier potassium current induced by hydrogen peroxide in rabbit atrial myocytes

AIM: To study the protective effect of piperine on abnormalityies of inward rectifier potassium current (I_K1) and ultra rapid delayed rectifier potassium current (I_KUr) induced by hydrogen peroxide (H₂O₂) in single rabbit atrial myocytes. METHODS: The technique of whole-cell patch-clamp was used to study the effect of H₂O₂ at concentration of 50 μmol/L on I_K1 and I_KUr in single rabbit atrial myocytes. The protective effect of pretreatment with piperine (7 μmol/L) was also observed. RESULTS: The piperine at concentration of 7 μmol/L had no significant effect on I_K1 and I_KUr and their channel dynamics. In the presence of H₂O₂ at concentration of 50 μmol/L, the peak currents of I_K1 and I_KUr reduced significantly (P<0.05).The steady-state activation curve of I_KUr was shifted right, the steady-state inactivation curve of I_KUr was shifted left, and the recovery from inactivation of I_KUr was shifted downward. The I_KUr showed frequency-dependent characteristics. Piperine at concentration of 7 μmol/L significantly alleviated the inhibitory effect of H₂O₂ on I_K1 and I_KUr (P<0.01). In addition, piperine protected against the changes of I_KUr dynamics induced by H₂O₂. CONCLUSION: Piperine alleviates the abnormalities of I_K1 and I_KUr induced by oxidative stress in atrial myocytes.     

Effect of garlicin on sodium channel current in rat ventricular myocytes

AIM: To observe the effect of garlicin on sodium channel(I_Na) in isolated ventricular myocytes of rats. METHODS: The ventricular myocytes of rats were obtained by enzymatic dissociation and treated with different concentrations of garlicin. The change of I_Na was recorded by the technique of whole-cell patch clamp recording.RESULTS: Garlicin decreased the I_Na of isolated ventricular myocytes in a dose- and voltage-dependent manner. The current density was elevated to peak under the condition that the membrane voltage was -40 mV before treated with garlicin. The current density was decreased by 48% from peak after treated with 500 μmol/L garlicin . No significant change of the active curve with the use of garlicin was observed. The median inactive voltages of the inactive curves before and after garlicin treatment were (-88.61±9.60) mV and (-103.03±8.90) mV (P<0.01), respectively, and the slopes were -7.85±0.88 and -7.55±2.75 (P>0.05), respectively, indicating that garlicin made a shift to the negative direction. CONCLUSION: Garlicin treatment induced the current density-voltage curve of I_Na to shift up and significantly decreased the current density. The inactive curve of sodium channel moved to the left, while the current density was not decreased after treated with garlicin. Garlicin blocks sodium channel in its inactive state in a dose- and voltage-dependent manner.     

Persistent sodium current in ventricular myocytes and its clinical meaning

A persistent sodium current (INa.p) in ventricular myocytes is produced by the sodium channel activity after the transient sodium current. Most studies suggest that the essence of persistent sodium current is produced by the modification of inactivation gate of transient current channel or the loss of this gate. The persistent sodium current, which inactivation is slow, contributes to the plateau period of action potential and pacemaking current. Its distribution density is different across the ventricular wall. The investigation suggests that INa.p is regulated by the oxygen sensor on membrane, action of nitric oxide or β-subunit and so on. Hypoxia increases the persistent sodium current, which plays a significant role in early afterpolarization and arrhythmogenesis in some pathological conditions and inherited disease. The role of persistent sodium current in heart failure is still full of argumentation. Persistent sodium current and transient sodium current exist in different reaction to some regents. The above results indicate that it is significant to acknowledge the disturbance of clinical electrophysiology through investigating change and mechanisms of INa.p. Morever, as a novel target of anti-arrhythmias drugs, this current should be paid more attention.     

Effect of breviscapin on INa channel current in isolated rat ventricular myocytes

AIM: To investigate the effects of breviscapine on INa channel in isolated rat ventricular myocytes. METHODS: Single cell of rat ventricular myocyte was isolated by enzymatic dissociation. The whole-cell patch-clamp recording technique was used to observe the change of INa channel current influenced by breviscapine. RESULTS: Breviscapine decreased the INa channel current in a dose-dependent and voltage-dependent manner in rat ventricular myocytes. The current-voltage curve was significantly decreased. Breviscapin at concentrations of 1, 3, 30, 100 mg/L respectively decreased INa current density, which were (7.98±0.60)%, (37.73±2.31)%, (65.58%±2.90)% and (88.09±5.60)%, respectively. INa was inhibited in a voltage-dependent manner, showing a significant attenuating effect at test potentials from -30 mV to 0. The INa inactivation curve was shifted to left and the activation curve was shifted to right. Breviscapine step down the recovery curve significantly. CONCLUSION: Breviscapine concentration-dependently decreased INa channel current in rat ventricular myocytes.     

Effect of hypoxia on persistent sodium current in ventricular myocytes from 3-week infarcted rat heart

AIM: To investigate the effect of hypoxia on persistent sodium current (INap) in single ventricular myocyte isolated from acute myocardial infarction (AMI) heart of rats and to study the mechanisms of cardiac arrhythmias that occur after AMI. METHODS: AMI model was induced by ligating the left anterior descending coronary artery in rats. The whole-cell patch clamp technique was used to record the current in epicardial myocytes in infarcted region from rats at 3 week after AMI. RESULTS: In normoxic conditions, the current density of INap in cardiomyocytes of fake operation (FO) and AMI hearts was 0.144±0.022 pA/pF (n=9), 0.121±0.013 pA/pF (n=9，P<0.01)， respectively, which was blocked by tetrodotoxin (TTX). The amplitude of INap was gradually increased with the prolongation of hypoxia time, but the increase in extent of INap in FO cells was significant bigger than that in AMI cells. The INap was blocked by 1 mmol/L glutathione. CONCLUSIONS: After AMI, the amplitude of INaP in infarcted and noninfarcted myocardium showed differences both in normoxic and hypoxic conditions, which increased dispersion of repolarization. This may be one of the reasons of reentrant ventricular arrhythmias that occur after AMI.     

Effects of endothelin and endothelin receptor antagonist on funny current and its gene expression in neonatal rat ventricular myocytes

AIM: To analyze the effect of endothelin-1 (ET-1) and ET-1 receptor antagonist on funny current (If) and its gene (hyperpolarization-activated cation channel, HCN) expression in neonatal rat ventricular myocytes. METHODS: Fresh ventricular myocytes were isolated from 1-3 d rats. The expression of If gene was measured by real-time quantitative polymerase chain reaction (real-time PCR). If was recorded and studied through whole-cell patch clamp. The cardiomyocytes were stimulated by ET-1 (0, 1, 10, 100 nmol/L) for 3 hours, or ET-1 (100 nmol/L) for 0, 0.5, 1, 3, 6 hours or ET-1 plus ETA- or ETB-receptor antagonist (BE-18257B or IRL-1038), respectively. RESULTS: HCN1, HCN2, HCN3, HCN4 represented (0.23±0.01)%, (83.58±0.04)%, (0.79±0.01)%, (15.44±0.01)% of total HCN mRNA, respectively. If was recorded. When cells were stimulated by ET-1 (10, 100 nmol/L), HCN2 was significantly increased by 0.1, 2 times and HCN4 was increased by 0.1, 0.5 times. When cells were stimulated for 0.5, 1, 3 and 6 hours, HCN2 was significantly increased by 0.3, 1, 5, 5.1 times and HCN4 was increased by 0.1, 0.6, 2, 2.1 times. The treatment of the combination of ET-1 plus BE-18257B significantly decreased HCN2 and HCN4 level. However, HCN1 and HCN3 had no statistically significant change. If would be increased by ET -1 and this effect was reverted by BE-18257B. IRL-1038 had no effects on If and HCN. CONCLUSION: (1) HCN2 and HCN4 represent a large amount of total HCN mRNA in neonatal rat ventricular myocytes. (2) If and the expression of HCN2 and HCN4 are increased by ET-1, this effect is reverted by BE-18257B.     

Effects of safflor injection on expression of cyclooxygenase-2 mRNA during lung ischemia/reperfusion injury in rabbits

AIM: To investigate the effects of safflor injection (SI) on expression of cyclooxygenase-2 mRNA during lung ischemia/reperfusion injury (PIRI) in rabbits. METHODS: Rabbit lung model of ischemia/reperfusion injury was constructed in vivo. The rabbits were randomly divided into three groups: sham-operation group (group S), ischemia-reperfusion group (group I/R) and ischemia/reperfusion plus safflor injection group (group SI). The lung tissue sampled at the end of the experiment was assayed for wet/dry weight ratio (W/D), injured alveoli rate (IAR) and observed ultrastructure changes under electron microscope. The expressions of COX-1 and COX-2 were measured by immunohistochemistry (IHC). The expression of COX-1 mRNA and COX-2 mRNA were observed by in situ hybridization (ISH). RESULTS: The value of W/D and IAR was much higher in I/R group, but decreased in SI group. Electron microscope showed obvious ultrastructure injury brought by PIRI in I/R group, which was greatly attenuated in SI group. The IHC and ISH demonstrated that COX-2 and COX-2 expressions in pulmonary tissue of I/R group were significantly higher than those in S group (P<0.01). The difference of COX-1 and COX-1 expressions in pulmonary tissue was not observed among three groups. CONCLUSION: The lung ischemia-reperfusion insult induces the up-regulation of COX-2 in lung. Safflor injection may attenuate lung ischemia-reperfusion injury through inhibiting COX-2 expression.     

Effects of prostaglandin I2 on mesenteric microcirculation and property of hemorheology in rabbits with renal ischemia/reperfusion injury

AIM: To explore the effects of prostaglandin I2 (PGI2) on mesenteric microcirculation and hemorheology during renal ischemia/reperfusion (IR) injury. METHODS: 36 rabbits were randomly distributed into the sham operated group (sham group)， renal ischemia/reperfusion injury group (IR group) and PGI2+IR group（PGI2 group）. IR group received clamping for 60 min followed by 120 min of reperfusion. A microcircular microscope image analysis system was used to study the changes of mesenteric microcirculation and hemorheology at 60 min of ischemia and 120 min of reperfusion, respectively， while the blood samples were obtained for the measurement of hemorheological indexes. RESULTS: ① In IR group during the period of renal IR， the number of adhesive leukocytes and microthrombus， hemorrhage and hemorheological indexes such as blood viscosity， plasma viscosity， blood reduction viscosity， hematocrit， erythrocyte aggregation index， erythrocyte sedimentation rate， erythrocyte sedimentation rate K and plasma fibrinogen were significantly higher， while microvascular diameters， blood flow velocity and erythrocyte deformation index were significantly lower compared with sham group (P＜0.01 or P＜0.05). ② PGI2 5-40 ng·kg-1·min-1) affected the indexes of mesenteric microcirculation and hemorheology to different extent. In 10 ng·kg-1·min-1 PGI2 group， the diameters of arteriole and venule， blood flow velocity， the number of adhesive leukocytes， microthrombus， hemorrhage and hemorheological indexes significantly changed， compared with IR group (P＜0.01 or P＜0.05). Except that microvascular diameters increased remarkably （P＜0.01）， others showed no significant difference compared to sham group （P＞0.05）. CONCLUSIONS: PGI2 ameliorates the disturbance of mesenteric microcirculation and hemorheology caused by renal IR injury with the best effect at 10 ng·kg-1·min-1.     

Effect of platelet activating factor on the action potential and potassium currents in guinea-pig ventricular myocytes

AIM: To investigate the effects of platelet activating factor (PAF) on the action potential and potassium currents in guinea-pig ventricular myocytes. METHODS: By using whole-cell patch clamp technique, the effects of PAF on APD₉₀, I_K1 and I_K were investigated in enzymatically dispersed single guinea-pig ventricular myocytes. RESULTS: With 5 mmol/L ATP in the pipette electrode, 1 μmol/L PAF increased APD₉₀ from (225.8±23.3) ms to (352.8±29.8) ms (n=5, P<0.05), decreased I_K1 and I_K tail currents from (-6.1±1.3) nA to (-5.6±1.1) nA (n=5, P<0.05) at -120 mV and from (173.5±16.7) pA to (152.1±11.5) pA (P<0.05, n=4) at +30 mV, respectively. In contract, without ATP in the pipette electrode, 1 μmol/L PAF shortened APD₉₀ from (153.0±24.6) ms to (88.2±19.4) ms (n=5, P<0.01). Incubation of myocytes with 1 μmol/L glibenclamide, a blocker of I_KATP restored prolongation of APD induced by PAF. CONCLUSION: In guinea-pig ventricular myocytes, with 5 mmol/L ATP in the pipette, PAF prolonged APD partly due to the inhibition of I_K and I_K1, while with 0 mmol/L ATP in the pipette, PAF induced an activation of I_KATP, hence a decrease in APD was observed. Therefore, PAF might amplify the heterogeneity between ischemia and normal cardiac myocytes during ischemic reperfusion, which might play a vital role in the pathogenesis of the arrhythmias induced by ischemia/reperfusion.     

Effects of resveratrol on the L-type calcium current by protein kinase G pathway in isolated guinea pig ventricular myocytes

AIM: To investigate the effects of resveratrol on the L-type calcium current in isolated guinea pig ventricular myocytes. METHODS: The whole cell patch clamp method was used. RESULTS: （1）Resveratrol (1, 50, 100 μmol/L) reduced the I_Ca-L by 18.31%±3.15%, 56.20%±2.50% and 84.51%±4.01% in a concentration-dependent manner (n=5, P<0.05). But it has no change on I-V shape of I_Ca-L. (2) 8Br-cGMP (100 μmol/L), an activator of protein kinase G(PKG), deduced the density of I_Ca-L by 10.50%±1.11%. Applying resveratrol and 8Br-cGMP simultaneously decreased the I_Ca-L significantly by 87.58%±3.49％ (n=6, P<0.05). (3) 5 μmol/L H8, a PKG inhibitor, inhibited the decrease in I_Ca-L caused by resveratrol. CONCLUSION: Resveratrol inhibits I_Ca-L in guinea pig ventricular myocytes, and this inhibitory effect involves the PKG pathway.     

Effects of panax notoginseng saponins on pneumocyte apoptosis and Fas/FasL expression in rabbits with lung ischemia/reperfusion injury

AIM: AIM: To explore the relationship between apoptosis in the lung tissues and lung ischemia/reperfusion injury, and observe effects of panax notoginseng saponins (PNS) on apoptosis in lung ischemia/reperfusion injury. METHODS: Single lung in situ ischemia/reperfusion animal model was used. Eighty four Japanese white rabbits were randomly divided into control group (control), ischemia/reperfusion 1 h group (IR1h), IR3h, IR5h, Panax Notoginseng Saponins 1 h group (PNS1h), PNS3h and PNS5h. TUNEL, immunocytochemistry and in situ hybridization techniques were used to observe apoptosis and Fas/FasL expression in various phases of lung ischemia/reperfusion. RESULTS: Cell apoptosis in lung tissues were significantly high, Fas/FasL mRNA and its protein were up-regulated in lung tissues of lung ischemia/reperfusion injury compared with control (all of P<0.01). The PNS suppressed apoptosis as well as expression of Fas/FasL mRNA and its protein (P<0.05 or P<0.01, respectively). There was a significant correlation between expression of Fas/FasL protein, Fas/FasL mRNA and cell apoptosis (r=0.540，0.658，0.668，0.686；all P<0.01). CONCLUSIONS: Activation of Fas/FasL system and its initiating cell apoptosis of lung tissues may contribute to the pathogenesis of lung ischemia/reperfusion injury. The protective effects of PNS include suppressing the activation of Fas/FasL system and blocking apoptosis in lung tissues in lung ischemia/reperfusion injury.     

Effects of progesterone on water,sodium, potassium and calcium contents in striatum of rats with focal cerebral ischemia/reperfusion

AIM: To explore the neuroprotective action of progesterone(PROG), which has been proved to be a "neuroactive steroid". METHODS: The model of focal cerebral ischemia was established in rats by reverserble inserting a nylon thread with a diameter of 0.2 mm into the anterior cerebral artery through the internal carotid artery. The effect of PROG was assessed by determining water,sodium, potassium, and calcium contents in striatum of rats subjected to 2 h ischemia followed by 22 h reperfusion. RESULTS: The water,sodium,and calcium contents of middle cerebral artery occlusion(MCAO) striatum were obviously higher,the potassium content was obviously lower than those of non-MCAO striatum in I/R and DMSO groups,but there was no significant difference between these two groups.Compared with the result in I/R and DMSO groups , water, sodium and calcium contents significantly decreased, but potassium(P＜0.01) obviously elevated in MCAO striatum in the PROG-pretreated group and PROG-pre or posttreated group.There was also significant reduction in water and sodium, but not significantly changed in calcium and potassium in PROG-posttreated group. The water,sodium,potassium,and calcium contents of MCAO striatum in each PROG-treated group were not remarkably different in comparision with those in dexamethasone treatment group(P＞0.05). CONCLUSION: Treatment with PROG can significantly reduce the striatal injury of rats with cerebral ischmia-reperfusion.