RISK signaling pathway in myocardial preconditioning and postconditioning

The anti-apoptotic pro-survival kinase signaling cascades, phosphatidylinositol-3-OH kinase (PI3K)-Akt and p42/p44 extra-cellular signal-regulated protein kinases (ERK 1/2), which have been termed the reperfusion injury salvage kinase (RISK) pathway, are involved in cellular survival. In myocardial ischemic preconditioning, pharmacological preconditioning, ischemic postconditioning and pharmacological postconditioning, the activation of these kinase cascades at the time of reperfusion has been demonstrated to confer cardioprotection against reperfusion-induced injury. Targeting the RISK signaling pathway may provide a novel strategy to salvaging viable myocardium and limiting infarct size during myocardial ischemia-reperfusion.     

Protective effect of ischemic preconditioning on rat brain with ischemia/reperfusion injury

AIM:To study whether ischemic preconditioning(IPC) has a protective effect against ischemia/reperfusion(I/R) injury in brain, and the possible relationship between IPC and the regulating function of microcirculation.METHODS:The I/R models were established both in I/R and IPC groups of Sprague-Dawley rats. Additional procedure was performed of short term cerebral ischemic preconditioning in IPC group 24 hours before I/R. Skull windows were performed through which microcirculation features were measured before ischemia, during ischemia, and reperfusion. Finally, brains were cut into slices and stained with red tetrazoline(TTC).RESULTS:Most TTC stained brains in I/R group presented irregular palely red areas which were few in IPC group. Compared with I/R group, IPC group presented relatively increase in accumulated length of capillaries, mean cerebral microcirculatory perfusion, and microcirculatory velocity in ischemic and reperfusion phase. There was no-reflow phenomenon in I/R group in reperfusion phase, which was substituted by the course of increasing reperfusion in IPC group.CONCLUSIONS:IPC could relieve the reduction of tissue perfusion during ischemia and the no-reflow phenomenon during reperfusion by improving the regulating function of microcirculation, which relatively promote the opening of capillaries and accelerating of microvascular flow, therefore protect brain from I/R injury.     

Effect of erigeron on intercellular adhesion molecule-1 and its mRNA expression during cerebral ischemia and reperfusion in rats

AIM: To investigate the effect of erigeron on intercellular adhesion molecule-1 (ICAM-1) and mRNA expression during cerebral ischemia/reperfusion. METHODS: The rat models of middle cerebral artery (MCA) focal cerebral ischemic reperfusion were established with the suture method in the study. The ICAM-1 mRNA and protein expression were measured by RT-PCR and immunohistochemistry techniques, respectively. RESULTS: By down-regulating the expression of ICAM-1 protein and mRNA and alleviating inflammation in cerebral ischemic region, erigeron exerted a protective effect in cerebral ischemia and reperfusion. CONCLUSION: The results suggest that erigeron protects the brain against cerebral ischemia and reperfusion injury via inhibiting ICAM-1 expressino.     

Effects of cerebral ischemia and postconditioning on signaling molecules PERK and GRP78 in hippocampus tissue of tree shrew during endoplasmic reticulum stress

AIM: To investigate the effects of cerebral ischemia and postconditioning on protein kinase R-like endoplasmic reticulum kinase (PERK) and glucose-regulated protein 78 (GRP78) in the hippocampus tissue of tree shrew during endoplasmic reticulum stress and the mechanism of post-conditioning protecting the brain from damage. METHODS: The focal cerebral ischemic model was duplicated by photochemical reaction in tree shrew and the postconditioning was induced by alternatively occluding and opening the carotid artery of ischemic side for 3 cycles (5 min each cycle) at 3.5 h after ischemia. The damage and ultrastructural changes of the hippocampal neurons were observed by HE staining. The expression of PERK and GRP78 at mRNA and protein levels in the hippocampal tissue at different time points after cerebral ischemia and postconditioning was determined by RT-PCR, immunohistochemistry and Western blot. RESULTS: The injuries of hippocampal neurons were aggravated with prolonged cerebral ischemia, which was most severe at 24 h after ischemia while the postconditioning alleviated these damages correspondingly. The expression of PERK at mRNA and protein levels was upregulated at 4 h, 24 h and 72 h after ischemia (P<0.05), while postconditioning downregulated the expressions of PERK at ischemia and postconditioning 4 h (IP4 h) gruop and IP24 h group (P<0.05). The expression of GRP78 at mRNA and protein levels was not changed at 4 h, 24 h and 72 h after ischemia, while postconditioning upregulated the expressions of GRP78 at IP24 h group (P<0.05). CONCLUSION: The focal thrombotic cerebral ischemia activates the endoplasmic reticulum stress in ischemic hippocampus of tree shrews, leading to the changes in mRNA and protein expression of PERK in the PERK/eIF2α signal transduction pathway. The postconditioning treatment alleviates endoplasmic reticulum stress and neuronal damages by downregulating PERK and upregulating GRP78, thereby protecting the brain from injury.     

Cardioprotection of ischemic postconditioning against ischemia/reperfusion injury in isolated rat hearts

AIM: To investigate the protective role of postconditioning in myocardial ischemia/reperfusion in rats and its mechanisms. METHODS: Cardiac contractility was analyzed by the Langendorff method. Infarct size was determined by dual staining with triphenyltetrazolium chloride and Even's blue dye, and the cardiac arrhythmia was evaluated. postconditioning was conducted by 3 cycles of 30 s ischemia followed by 30 s of reperfusion at the beginning of subsequent persistent reperfusion. RESULTS: Left ventricular systolic pressure (LVSP) and maximal rise rate of ventricular pressure (+dp/dt_max) were higher during reperfusion in postconditioning group compared with control. postconditioning reduced the infarct size in ischemia/reperfusion rat hearts. The cardiac arrhythmia score was decreased in postconditioning group in the first 10 min of reperfusion followed by ischemia compared to control group. postconditioning had similar cardioprotective effect as preconditioning. 5-HD, a selective mitochondrial ATP-sensitive potassium channel (mitoK_ATP) inhibitor, blocked the amelioration of contract function provided by postconditioning. It also abolished the protective effect of postconditioning on cardiac arrhythmia score and infarct size. CONCLUSION: The results show that postconditioning has cardioprotective effect and attenuates reperfusion injury in ischemic heart. The effect might be partly through the activation of mitoK_ATP channel.     

Postconditioning modulates TLR4 expression in hippocampus of tree shrews with thrombotic cerebral ischemia

AIM: To observe the effects of thrombotic cerebral ischemia and postconditioning on the expression of toll-like receptor 4 (TLR4) in hippocampus of tree shrews.METHODS: The model of thrombotic focal cerebral ischemia was established by photochemical reaction.Four hours after the onset of photochemical reaction, ischemic postconditioning was induced by 3 repeated cycles of carotid artery occlusion for 5 min and reperfusion for 5 min. The histological changes of hippocampus (by HE staining), TLR4 protein level (by Western blotting) and TLR4 mRNA expression (by semiquantitative RT-PCR) were observed.RESULTS: The extensive neuronal degeneration in hippocampus was observed from 4 h to 72 h and peaked at 24 h after cerebral ischemia, but was significantly attenuated after postconditioning. Cerebral ischemia caused a progressive increase in the expression of TLR4 protein at 4 h and 24 h (P<0.05), and decreased at 72 h (P<0.05). In contrast to ischemia groups, postconditioning decreased the expression of TLR4 protein at 4 h and 24 h (P<0.05), but an increase in the expression of TLR4 at 72 h (P<0.05) was observed. Simultaneously, the level of TLR4 mRNA in hippocampus showed the tendency of approximate variation in accordance with the protein expression.CONCLUSION: The expression of TLR4 increases by cerebral ischemia. The protection mechanisms of postconditioning may be associated with modulating TLR4 expression.     

Preconditioning with 3-nitropropionic acid induces rat cerebral ischemic tolerance and increases expression of glucose transporter 1 and glucose transporter 3

AIM: To explore the mechanism of 3-nitropropionic acid (3-NPA) preconditioning that induces cerebral ischemic tolerance in rats by affecting the expression of brain-type glucose transporters (GLUT1 and GLUT3) at mRNA and protein levels in cerebral tissues.METHODS: The male SD rats were used in the experiments and divided randomly into sham operation group (sham group, n=4), control group of 3-NPA preconditioning (3-NPA group, n=4), cerebral ischemia group (M group, n=16) and 3-NPA preconditioning group (IPC group, n=16). M group and IPC group were further divided into 4 subgroups according to the different reperfusion time(4 h, 12 h, 24 h and 48 h). All rats were killed at the corresponding time points. The cerebral tissues in the ischemic side (left) and coronal intermediate 1/3 of cortex were collected. The protein levels and mRNA expression of GLUT1 and GLUT3 were determined by Western blotting and RT-PCR. RESULTS: Compared with M group, the ischemic reperfusion and 3-NPA preconditioning induced the upregulation of GLUT1 and GLUT3 at protein levels with significant differences (F=5.848, P<0.05 and F=6.295, P<0.05, respectively), especially after ischemia-reperfusion for 48 h. The mRNA expression of GLUT1 in IPC group began to increase at 4 h, peaked at 48 h after reperfusion, with significant difference as compared to M group at the corresponding reperfusion time points in each group or sham group. In contrast, the mRNA expression of GLUT3 in IPC group increased at 24 h, and was the highest at 48 h as compared to cerebral ischemia group at the corresponding reperfusion time points or sham group.CONCLUSION: 3-NPA preconditioning increases the expression of GLUT1 and GLUT3 at protein and mRNA levels to maintain the energy supply in brain tissues, indicating a cerebral protective mechanism.     

Intestinal ischemic postconditioning attenuates acute lung injury induced by intestinal ischemia/reperfusion in rats

AIM: Previous study has shown that brief period of repetitive superior mesenteric artery (SMA) occlusion and reperfusion applied at the onset of reperfusion, ischemic postconditioning (IPo), attenuates intestinal injury after intestinal ischemia/reperfusion (I/R). This study tested the hypothesis that IPo would attenuate intestinal I/R-induced acute lung injury which is comparable to ischemic preconditioning (IPC) and the brief period of postconditioning applied at the onset of reperfusion is critical to pulmonary protection by IPo. METHODS: Rat intestinal I/R injury was produced by clamping SMA for 60 min followed by 60 min of reperfusion. The rats were randomly allocated into one of five groups based upon the intervention (n=8): sham operation (sham): sham surgical preparation including isolation of the SMA without occlusion was performed; injury: there was no intervention either before or after SMA occlusion; ischemia preconditioning (IPC): the SMA was occluded for 10 min followed by 10 min of reperfusion before prolonged occlusion; ischemia postconditioning (IPo): 3 cycles of 30 s reperfusion-30 s reocclusion were imposed immediately upon reperfusion (3 min total intervention); delayed postconditioning (delay): clamping was completely released for full reperfusion for 3 min (the duration of the IPo algorithm), after which 3 cycles of 30 s occlusion and reperfusion were applied. RESULTS: Histological results showed severe damages in rat lungs in the injury group evidenced by increased lung wet/dry weight ratio and pulmonary permeability index, which was accompanied by increases in the levels of plasma TNF-α and IL-6, the pulmonary malondialdehyde (MDA), and the pulmonary myeloperoxidase (MPO) activity, and a decrease in superoxide dismutase (SOD) activity. IPo, not delayed IPo, significantly attenuated lung injury and improved the above variables, which was comparable to IPC. CONCLUSION: IPo at onset of reperfusion reduces acute lung injury induced by intestinal I/R, which may be mediated, in part, by inhibiting oxidant generation, filtration of neutrophils and releases of proinflammatory mediators. The early period of reperfusion in the rat model is critical to pulmonary protection by IPo. IPo may improve outcome in clinical conditions associated with intestinal I/R.     

Effects of ginsenoside Rg1 of Panax notoginseng on brain tissue injury and Nrf2/HO-1 signal pathway after cerebral ischemia/reperfusion in mice

AIM:To observe the effects of ginsenoside Rg1 of Panax notoginseng on brain tissue injury after mouse cerebral ischemia/reperfusion(I/R), and to explore the mechanisms involving nuclear factor E2-related factor 2 (Nrf2)/heme oxygenase 1 (HO-1) signal pathway. METHODS:C57BL/6 mice were randomly divided into sham group, cerebral I/R group, ginsenoside Rg1+cerebral I/R group and edaravone+cerebral I/R group. Ginsenoside Rg1 was successively administered for 3 d. One hour after final administration, bilateral common carotid arteries were ligated to induce brain tissue injury for 20 min, and then reperfusion for 24 h. Edaravone, a drug for anti-oxidative stress injury in the treatment of ischemic cerebro-vascular disease, was used as a positive control. The brain tissues were obtained to determine the neural cellular pathology in hippocampal CA1 region. The mRNA expression of Nrf2 and HO-1 was detected by RT-PCR. The protein levels of Nrf2 in the nucleus and cytoplasm and HO-1 in the whole cells in the brain tissues were measured by Western blotting. RESULTS:After ischemia/reperfusion for 24 h, the pathological injury in the neural cells was obvious, and the cell survival rate decreased. Ginsenoside Rg1 and edaravone attenuated the neural cell injury, and significantly increased the cell survival rate. After ischemia/reperfusion for 24 h, the mRNA expression of Nrf2 and HO-1 significantly increased in the brain tissues. The protein levels of Nrf2 in the nucleus and cytoplasm in the brain tissues were increased, the nuclear translocaition rate and the protein expression of HO-1 also increased. Ginsenoside Rg1 and edaravone both decreased the protein levels of Nrf2 in the cytoplasm of the brain tissues, increased that in the nucleus, and also increased Nrf2 nuclear translocation rate and the protein expression of HO-1. The effect of edaravone was higher than that of ginsenoside Rg1, but they had no significant effect on the mRNA expression of Nrf2 in the brain tissues. CONCLUSION: Ginsenoside Rg1 has the effect of anti-brain tissue injury on cerebral ischemia/reperfusion. The mechanisms may be related to activating the Nrf2/HO-1 signal pathway, promoting Nrf2 synthesis and nuclear translocation, thus promoting the expression of downstream antioxidant protein HO-1.     

Effect of cholecystokinin-octapeptide on focal cerebral ischemia/reperfusion injury in rats

AIM:To examine the effect of cholecystokinin-octapeptide (CCK-8) on focal cerebral ischemia/reperfusion injury and its underlying mechanisms.METHODS:By using the suture model of focal cerebral ischemia and reperfusion, the effects of intracerebroventricular (icv) injection of CCK-8 and proglumide, nonselective CCK receptors antagonist, on the infarct size, regional cerebral blood flow (rCBF), and the levels of nitric oxide (NO), malondialdehyde (MDA) were observed in different brain regions of rats subjected to 1 h focal cerebral ischemia followed by 24 h reperfusion.RESULTS:(1) pretreatment with different doses of CCK-8 (0.3 μg,1.0 μg,2.0 μg or 4.0 μg) could attenuate the infarct size, but the statistically significant effects of CCK-8 were obtained only at the doses of 1.0 μg and 2.0 μg(P＜0.05). The neuroprotective effects of CCK-8 were blocked by pretreatment with proglumide. Administration of proglumide alone could worsen the ischemia/reperfusion injury. (2) CCK-8 (1.0 μg) inhibited the increase in NO, MDA levels in the ischemic core, and also inhibited the increase in NO level in the ischemic penumbra. The rCBF in the CCK-8 group was significantly higher than the normal value at 24 h after reperfusion (P＜0.05).CONCLUSIONS:These results suggest that both endogenous and exogenous CCK-8 alleviate focal cerebral ischemia/reperfusion injury. Such an action may be associated with inhibition of free radical-induced injuries and the improvement in rCBF.     

Effects of ischemic postconditioning on sizes of myocardial infarction induced by ischemia/reperfusion and PKCα expression in rats

AIM: To observe the effects of ischemic postconditioning on the sizes of myocardial infarction induced by ischemia/reperfusion (I/R) and expression of protein kinase C-α (PKCα) in rats. METHODS: The infarction sizes (IS) were measured with Evan’s and TTC dye, and the expression of PKCα in myocardial tissue was investigated by immunohistochemistry. RESULTS: Compared with the I/R group, the IS was reduced significantly (P<0.01), and the expression of PKCα increased significantly in IPC and IPTC groups (P<0.01). There was no significant difference between IPC and IPTC groups. CONCLUSIONS: The postconditioning is as effective as preconditioning in reducing infarct size, and the expression of PKCα may be one of the potential mechanisms of reducing the infarction sizes.     

Inhibitory effect of ischemic postconditioning on autophagy induced by focal cerebral ischemia reperfusion in rats

AIM: To investigate the effect of ischemic postconditioning (IPC) on autophagy induced by focal cerebral ischemia reperfusion (I/R) in rats. METHODS: Healthy male SD rats were assigned randomly into sham-operation (sham) group, I/R group and IPC group with 10 rats in each group. The rats in sham group were only exposed the right common, internal and external carotid artery surgically. The rats in I/R group were subjected to right middle cerebral artery occlusion (MCAO) by the modified Longa suture method for 2 h followed by 24 h of reperfusion. The rats in IPC group were subjected to MCAO for 2 h followed by reperfusion of the ipsilateral common carotid artery occlusion for 10 s for 5 episodes, and then reperfusion for 24 h. Autophagy was obeserved by transmission electron microscopy (TEM). The protein levels of mammalian target of rapamycin (mTOR), p-mTOR and microtubule associated protein light chain 3 (LC3)-II in brain tissue of the rats were determined by Western blot. Pathological changes of brain tissue were observed by HE staining. RESULTS: The protein levels of mTOR and p-mTOR in IPC group were significantly higher than those in I/R group (P<0.05). The expression of LC3-II in IPC group was significantly lower than that in I/R group (P<0.01). The cerebral infarction area and brain water content in IPC group were significantly lower than those in I/R group (P<0.01). HE staining showed that neurons degeneration and necrosis in IPC group were significantly alleviated compared with I/R group. TEM observation showed that IPC revealed fewer autophagosomes, with much less severe cell damage than that in I/R group. CONCLUSION: IPC reduces brain ischemia reperfusion damage by decreasing autophagy of brain cells, which might be related to the activation of mTOR.     

Protective effect of spermine on rats with acute cerebral ischemia/reperfusion injury

AIM: To study the effects and the possible mechanisms of exogenous spermine on the rats with acute transient focal cerebral ischemia/reperfusion (I/R) injury.METHODS: The rat model of focal cerebral ischemia/reperfusion was established by middle cerebral artery occlusion (2 h) and reperfusion (2 h). Healthy adult SD rats were divided into 5 groups;sham group,I/R group and spermine(4,20 and 40 mmol/L)groups.The degree of cerebral injury was evaluated by neurological deficit score, infracted volume, superoxide dismutase (SOD) activity and malondialdehyde (MDA) content. The morphological changes of the brain were observed by HE staining and electron microscopy. RESULTS: Compared with I/R group, the neurological deficit score, infracted volume and the content of MDA were decreased, the SOD activity was increased and the ultrastructural changes were improved in spermine-treated groups. CONCLUSION: Exogenous spermine has a protective effect against acute focal cerebral ischemia/reperfusion injury. The mechanisms may be related to scavenging free radical by spermine.     

Changes of intracellular Ca2+ in living brain slices during focal cerebral ischemia/reperfusion

AIM: The purpose of the present study was to detect intracellular Ca²⁺changes in living brain slices during focal cerebral ischemia/reperfusion (I/R) and reveal the role of intracellular Ca²⁺in the cerebral I/R injury. METHODS: The model of focal cerebral I/R was established in rats by reversible inserting a nylon thread, and dynamic change of intracellular Ca²⁺in brain slices was determined using laser confocal imaging system. RESULTS: ① Ca²⁺gradually enhanced with increase in ischemic time in cortex and striatum. ②At1h ischemia/10min reperfusion, Ca²⁺increased significantly in striatum, but Ca²⁺decreased at 3 h reperfusion compared with10min reperfusion. ③ Ca²⁺markedly enhanced at 6 h ischemia compared with1h ischemia, and after 3 h reperfusion Ca²⁺decreased, but was still higher than that in sham-operation group. ④The striatum is more sensitive than cortex to ischemia/reperfusion. CONCLUSION: Ca²⁺overload in the area of cortex and striatum may play an important role in cerebral ischemia/reperfusion injury in rats.     

Effect of adenosine infusion before ischemic preconditioning on immature myocardial reperfusion injury in neonatal rabbits

AIM and METHODS:To investigate the cardioprotective effect of adenosine infusion before ischemic preconditioning on immature myocardial reperfusion injury in rabbit heart. Isolated perfused working heart model were performed, all hearts were subjected to 2-hour global hypothermic ischemia and received intermittent cold cardioplegia perfusion.RESULTS:During reperfusion, the recovery of left ventricular systolic pressure, left ventricular end-diastolic pressure, +dp/dt_max, and -dp/dt_max of hearts received adenosine infusion before ischemic preconditioning were significantly improved, myocardial adenosine triphosphate and adenosine diphosphate content and superoxide dismutase activity were higher, the leakage of myocardial creatine kinase and the malondialdehyde content were lower, and myocardial water content was obviously less.CONCLUSION:These results suggest adenosine infusion before ischemic preconditioning enhances cardioprotection of ischemic preconditioning against immature myocardial reperfusion injury in the rabbit heart.     

Effects of Astragalus polysaccharide on expression of HSP70, PKB and P53 in rat cerebral cortex with cerebral ischemia and reperfusion

AIM:To explore the molecular effects of Astragalus polysaccharide(AP) on improving nervous functions and preventing neuronal apoptosis in rat cerebral cortex with cerebral ischemia and reperfusion. METHODS:One hundred and twenty male Wister rats were randomly divided into sham operation group(SOG), model groups(MG-1 d, 3 d and 7 d), low-dose AP treatment groups(L-APTG-1 d, 3 d and 7 d), and high-dose AP treatment groups(H-APTG-1 d, 3 d and 7 d). The right middle cerebral artery of the rats in MG and AGTG was intercepted by operation to induce ischemic brain injury. The rats in L-APTG and H-APTG were treated with AP at the doses of 5 mg/kg and 15 mg/kg by intraperitoneal injection, respectively. On the 1st day, 3rd day and 7th day after operation, those animals were sacrificed to collect the brain specimens for the study after cerebral blood flow reperfusion and determination of neurological deficit scores. The structural changes of the neurons were observed under electron microscope. Apoptosis was analyzed by flow cytometry. The protein levels of heat-shock protein 70(HSP70), protein kinase B(PKB) and P53 in cerebral corical neurons were determined by immunohistochemical staining and Western blotting. RESULTS:The neurological deficit scores and the apoptotic rate of cerebral cortical neurons in H-APTG were significantly lower than those in MG and L-APTG(P<0.05). The structures of the neurons in H-APTG, such as ribosome endoplasmic reticulum, nucleolus, Golgi complex, mitochondria, etc, were better than those in MG and L-APTG. On the 1st day, 3rd day and 7th day, the protein levels of HSP70 and PKB in cerebral cortical neurons in H-APTG were significantly higher than those in L-APTG, which were significantly higher than those in MG(P<0.05). However, the P53 protein level in H-APTG was significantly lower than that in L-APTG, which was significantly lower than that in MG(P<0.05). CONCLUSION:AP improves nervous functions and inhibits neuronal apoptosis during ischemia and reperfusion. The molecular mechanisms are associated with variations of protein expression in cerebral cortical neurons, such as promotion of HSP70 and PKB and inhibition of P53.     

Ischemic postconditioning ameliorates pia mater microcirculation in rats subjected to cerebral ischemia reperfusion

AIM:To investigate the ameliorative effect of ischemic postconditioning (I-postC) on pia mater microcirculation in rats subjected to cerebral ischemia reperfusion (I/R) and its mechanisms.METHODS:Thirty-two male Wistar rats were randomly divided into sham, I/R, I-postC, and ischemic preconditioning (IPC) groups.The global cerebral I/R injury was induced by shunting carotid artery in rats.Pia mater microcirculation and cerebral microcirculatory perfusion were measured after reperfusion.The content of soluble intercellular adhesion molecule-1 (sICAM-1) in plasma was detected using enzyme linked-immunosorbent assay (ELISA).Myeloperoxidase (MPO), malondialdehyde (MDA), and superoxide dismutase (SOD) in cerebral tissue were detected.The expressions of vascular endothelial cell cadherin (VE-cadherin) and NF-κB p65 in cerebral tissue were assayed by Western blotting.RESULTS:(1) The disturbance of the blood flow in microvessel induced by I/R was improved significantly by I-postC.In addition, I-postC alleviated significantly the decrease in diameters of microvesseles, cerebral microcirculatory perfusion and cerebral VE-cadherin content induced by I/R (P＜0.05).(2) sICAM-1 in plasma, MPO and MDA in cerebral tissue decreased, but SOD activity in cerebral tissue increased in I-postC group, compared with those in I/R group (P＜0.05 or P＜0.01).The over-expression of NF-κB p65 induced by I/R was relieved by I-postC (P＜0.05).CONCLUSION:I-postC ameliorates pia mater microcirculation in rats subjected to cerebral I/R through suppressing the activation of polymorphonuclear neutrophils mediated by ICAM-1.     

Ischemic postconditioning protects skeletal muscle from ischemia/reperfusion injury through improving microcirculation in rat hind limb

AIM: To investigate the effect of ischemic postconditioning (I-postC) on ischemia/reperfusion (I/R) injury of skeletal muscle and its microvasculatory mechanisms in rat hind limb. METHODS: Healthy male Wistar rats were randomly divided into three groups as follows (n=16): I/R group, I-postC group and ischemic preconditioning (IPC) group. I/R of right hind limb was induced by clamping right femoral artery. The effects of I-postC on oxygen saturation of hemoglobin (StO2), blood flow, microcirculation, hemodynamics, Wet/Dry ratio (W/D) and ultramicrostructure of skeletal muscle were detected on 12 h or 24 h after reperfusion. RESULTS: (1) Compared with I/R group, 12 h after reperfusion, W/D from I-postC group decreased 6.7% (P<0.05) and myofibrillae lysis of skeletal muscle and vacuolation of mitochondria attenuated than that in I/R group. 24 h after reperfusion,-dp/dtmax in I-postC group increased 10.46% (P<0.05). (2) It was also found that 24 h after reperfusion, blood velocity in venule increased 11.3% in I-postC group compared with that in I/R group (P<0.05), and internal diameter of arteriole and venule increased 39.8% and 24.1% compared with that in I/R group, respectively (P<0.01). No significant difference between I-postC and IPC groups (P>0.05) was found. CONCLUSION: I-postC protects the skeletal muscle against reperfusion injury by improving microcirculation.     

Effects of bFGF on neuronal apoptosis and fractalkine expression in cerebral ischemia/reperfusion rats

AIM: To study the effects of basic fibroblast growth factor (bFGF) on neuronal apoptosis and fractalkine expression in ischemic penumbra after cerebral ischemia/reperfusion in rats.METHODS: Thirty-six rats were randomly divided into 3 groups: sham operation group, ischemia/reperfusion group and bFGF group. The model of middle cerebral artery occlusion was established by the method of intraluminal filament blockage. The middle cerebral arteries were blocked for 1 h and then reperfused for 24 h. Neurological performances of all rats were scored with Bederson's standard. The brain tissues of the rats were stained and the average infarct volume was calculated. TUNEL method was used to determine the number of apoptotic neurons, and the expression of fractalkine was detected by the method of immunohistochemistry.RESULTS: The score of neurological performances in bFGF group was 2.23±0.59, lower than that in ischemia/reperfusion group (3.18±0.65). The number of apoptotic neurons in bFGF group (13.22±1.35) was lower than that in ischemia/reperfusion group (17.28±1.01, P<0.05), which was the lowest in sham operation group (0.91±0.65). Compared with sham operation group, the expression of fractalkine in ischemia/reperfusion group was decreased. The expression of fractalkine in bFGF group was mainly higher than that in ischemia/reperfusion group (P<0.05).CONCLUSION: Up-regulation of fractalkine may be one of the molecular mechanisms of bFGF to protect neurons against ischemia/reperfusion injury.