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It has been shown that ischemia preconditioning (IPC) can attenuate the myocardial injury induced by ischemic and reperfusion. But it was rarely used in clinic due to its inoperability. Previous studies indicate that electroacupuncture (EA) pretreatment can mimic myocardial ischemia preconditioning (MIPC) to produce cardioprotective effect. The activated adenosine A 2 b receptor has been proven to be involved in mediating the cardioprotection of IPC. In the studies on acupuncture analgesia, it was reported that adenosine receptor was activated by acupuncture stimulation, and acupuncture pretreatment can affect the acti-vities of intracellular A 2 b receptor. Based on those mentioned above, it is highly likely that the A 2 b receptor may also participate in the cardioprotection produced by acupuncture pretreatment. In this paper, we comprehensively reviewed relevant studies regarding 1) the cardioprotective effect of IPC and its limitations, 2) the similar cardioprotection produced by both acupuncture pre-treatment and IPC, 3) the mechanism underlying myocardial ischemic injury and intracellular calcium regulation, 4) the acti-vation of adenosine receptors and effects of acupuncture, 5) the relationship between adenosine receptors and intracellular calcium ion, and 6) the effect of acupuncture on adenosine receptors, so as to provide a novel assumption that A 2 b receptor may be a key factor in mediating the cardioprotection of acupuncture pretreatment. Our future research will systematically explore the me-chanism of acupuncture pretreatment in protecting ischemic myocardium from myocardial cell adenosine A 2 b receptor and intracellular calcium signal transduction related factors.
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<p><b>Background</b>Ischemia preconditioning (IPC) remains the most powerful intervention of protection against myocardial ischemia/reperfusion injury (IRI), but diabetes can weaken or eliminate its cardioprotective effect and detailed mechanisms remain unclear. In this study, we aimed to explore whether changes of autophagy in the diabetic condition are attributable to the decreased cardioprotective effect of IPC.</p><p><b>Methods</b>Sixty diabetic male Sprague-Dawley rats were randomly divided into the control (C), IRI, rapamycin (R), wortmannin (W), rapamycin + IPC (R + IPC), and wortmannin + IPC (W + IPC) groups. The in vivo rat model of myocardial IRI was established by ligaturing and opening the left anterior descending coronary artery via the left thoracotomy. Durations of ischemia and reperfusion are 30 min and 120 min, respectively. Blood samples were taken at 120 min of reperfusion for measuring serum concentrations of troponin I (TnI) and creatine kinase isoenzyme MB (CK-MB) using the enzyme-linked immunosorbent assay. The infarct size was assessed by Evans blue and triphenyltetrazolium chloride staining. The expressions of LC3-II, beclin-1, phosphoinositide 3-kinase (PI3K), mammalian target of rapamycin (mTOR), and P-Akt/Akt ratio in the ischemic myocardium were assessed by Western blotting.</p><p><b>Results</b>Compared to the IRI group, infarct size (56.1% ± 6.1% vs. 75.4 ± 7.1%, P < 0.05), serum cTnI (0.61 ± 0.21 vs. 0.95 ± 0.26 ng/ml, P < 0.05), and CK-MB levels (6.70 ± 1.25 vs. 11.51 ± 2.35 ng/ml, P < 0.05) obviously decreased in the W + IPC group. Compared with the C group, myocardial expressions of LC3-II (0.46 ± 0.04 and 0.56 ± 0.04 vs. 0.36 ± 0.04, P < 0.05) and beclin-1 (0.34 ± 0.08 and 0.38 ± 0.07 vs. 0.24 ± 0.03, P < 0.05) evidently increased, and myocardial expressions of mTOR (0.26 ± 0.08 and 0.25 ± 0.07 vs. 0.38 ± 0.06, P < 0.05), PI3K (0.29 ± 0.04 and 0.30 ± 0.03 vs. 0.38 ± 0.02, P < 0.05), and P-Akt/Akt ratio (0.49 ± 0.10 and 0.48 ± 0.06 vs. 0.72 ± 0.07, P < 0.05) markedly decreased in the IRI and R groups, indicating an increased autophagy. Compared with the IRI group, myocardial expression of beclin-1 (0.26 ± 0.03 vs. 0.34 ± 0.08, P < 0.05) significantly decreased, and myocardial expressions of mTOR (0.36 ± 0.04 vs. 0.26 ± 0.08, P < 0.05), PI3K (0.37 ± 0.03 vs. 0.29 ± 0.04, P < 0.05), and P-Akt/Akt ratio (0.68 ± 0.05 vs. 0.49 ± 0.10, P < 0.05) increased obviously in the W + IPC group, indicating a decreased autophagy.</p><p><b>Conclusions</b>Increased autophagy in the diabetic myocardium is attributable to decreased cardioprotection of IPC, and autophagy inhibited by activating the PI3K-Akt-mTOR signaling pathway can result in an improved protection of IPC against diabetic myocardial IRI.</p>
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Objective To evaluate the effect of electroacupuncture ( EA) preconditioning on hipp-ocampal I-kappa B-α ( IκB-α)∕nuclear factor κB ( NF-κB)∕intercellular adhesion molecule-1 ( ICAM-1) signaling pathway during cerebral ischemia-reperfusion ( I∕R) in mice. Methods A total of 120 healthy male C57BL∕6 mice, aged 10-12 weeks, weighing 20-25 g, were divided into 4 groups ( n=30 each) u-sing a random number table method: control group ( group C) , cerebral I∕R group ( group I∕R) , precondi-tioning with EA at non-acupoint+cerebral I∕R group ( group S+I∕R) and preconditioning with EA at Baihui acupoint + cerebral I∕R group ( group E+I∕R) . The cerebral I∕R injury model was established by occlusion of bilateral common carotid arteries followed by reperfusion for 72 h in mice anesthetized with halothane or chloral hydrate in group I∕R. Group S+I∕R received EA at the points 2 mm lateral to the acupoints of Baihui for 5 consecutive days, and then the cerebral I∕R injury model was established. Group E+I∕R received EA at Baihui acupoints with a sparse-dense wave at an intensity of 1 mA and a frequency of 2 Hz∕15 Hz for 30 min once a day for 5 consecutive days, and then the cerebral I∕R injury model was established. Neurobe-havioral score was assessed at 24 and 48 h of reperfusion. Then 5 mice in each group were sacrificed, and the hippocampal tissues were obtained and stained with haematoxylin and eosin for examination of the patho-logical changes in hippocampal CA1 region and for determination of the expression of IκB-α, NF-κB, ICAM-1, interleukin-6 ( IL-6) , IL-1β protein and mRNA by Western blot and real-time polymerase chain reaction, respectively. Results Compared with group C, neurobehavioral score was significantly in-creased, and the expression of hippocampal IκB-α, NF-κB, ICAM-1, IL-6 and IL-1βprotein and mRNA was up-regulated in I∕R, S+I∕R and E+I∕R groups ( P<0. 05) . Compared with group I∕R, neurobehavioral score was significantly decreased, and the expression of hippocampal IκB-α, NF-κB, ICAM-1, IL-6 and IL-1β protein and mRNA was down-regulated in group E+I∕R (P<0. 05), and no significant change was found in the parameters mentioned above in group S+I∕R (P>0. 05). Compared with group S+I∕R, neu-robehavioral score was significantly decreased, and the expression of hippocampal IκB-α, NF-κB, ICAM-1, IL-6 and IL-1β protein and mRNA was down-regulated in group E+I∕R ( P<0. 05) . Conclusion The mechanism by which EA preconditioning attenuates cerebral I∕R injury may be related to inhibiting activation of hippocampal IκB-α∕NF-κB∕ICAM-1 signaling pathway in mice.
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Objective To investigate the difference of late-phase of limb ischemia preconditioning (L-LIP) verse early-phase (E-LIP) on patients with percutaneous coronary intervention (PCI).Methods A total of 160 patients with unstable angina pectoris who were planned to undergo PCI were divided equally into two groups at random.The late-phase of limb ischemia preconditioning group (80 patients) were provided with L-LIP (three 5-minute inflations up to 200mmHg by applying the sphygmomanometer cuff around the right upper arm,followed by 5-min intervals of reperfusion,twice a day) 3 days before PCI.The Earlyphase of limb ischemia preconditioning group (80 patients) were provided with E-LIP (method as above)2 hours before PCI.Comparison of procedural parameters during PCI and the levels of cTnT,CK-MB,hs-CRP were made 24 hours after PCI.Estimation of the rate of adverse events at 1 year between the two groups was evaluated by Kaplan-Meier analysis.Results Compared to the E-LIP group,the rates of angina,arrhythmia and TIMI flow ≤ 2 during PCI were significantly lower in the L-LIP group (all P ＜ 0.05).At 24 hours after PCI,the levels of cTnT and CK-MB were declined more significantly in the L-LIP group[(11.52±2.41) pg/ml vs.(27.53±4.78)pg/ml,P =0.021;(14.11±2.87)Iu/L vs.(30.23±5.17)Iu/L,P =0.032].There was no difference in the level of hs-CRP between the 2 groups [(128±0.71)mg/dl vs.(1.33±0.69)mg/dl,P =0.742].The Kaplan-Meier survival curve showed that the incidence rate of adverse events in the L-LIP group at l year was lower than the E-LIP group (3.75％ vs.13.75％,P =0.024).Conclusions L-LIP is more effective to in protecting myocardial cell in patients with unstable angina pectoris undergoing elective PCI and may reduce the rate of future adverse event.
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[ ABSTRACT] AIM:To investigate the effects of maternal limb ischemic preconditioning ( LIP) on the mitochon-drial structures and functions of the hippocampal neurons induced by reoxygenation in the intrauterine distress fetal rats. METHODS:Pregnant rats (n=40) were randomly divided into 4 groups: sham (S) group, LIP group, fetal distress ( FD) group and LIP+FD group.Intrauterine ischemia model was established through the experimental design.The ultra-structure of the mitochondria in CA1 area of the hippocampus was observed .The mitochondrial membrane potential and re-active oxygen species ( ROS) were measured .The content of ATP and MDA in the hippocampus tissue was detected.The activity of Mn-SOD was observed.RESULTS:Compared with sham group, the ultrastructure of mitochondria in CA1 area of the hippocampus was damaged in FD group and LIP+FD group.The mitochondrial membrane potential, the content of ATP and the activity of Mn-SOD were decreased.However, the content of ROS and MDA was increased.Compared with FD group, the ultrastructure of mitochondria in CA1 area of the hippocampus was intact in LIP+FD group.Furthermore, the reduced mitochondrial membrane potential and ATP content were inhibited.The activity of Mn-SOD was increased, but the content of ROS and MDA was decreased in LIP+FD group.CONCLUSION:Limb ischemia preconditioning inhibits the damage the mitochondria of fetal hippocampal neurons induced by reoxygenation in the intrauterine distress fetal rats.
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Objective To investigate the role of inducible nitric oxide synthase (iNOS) in reduction of myocardial ischemia-reperfusion (I/R) injury by sufentanil preconditioning in rats. Methods Thirty adult male SD rats, weighing 250-330 g, were randomly divided into 5 groups ( n =6 each): sham operation group (group S),I/R group, sufentanil preconditioning group (group SF), sufentanil preconditioning + a specific inhibitor of iNOS S-methyl thiourea (SMT) group (group SF+ SMT) and S-methyl thiourea group (group SMT). In I/R,SF,SF+SMT and SMT groups, myocardial I/R was produced by occlusion of left anterior descending coronary artery for 30 min followed by 120 min reperfusion. Group SF received 30 min infusion of sufentanil 120 μg/kg via caudal vein 24 h before ischemia. Group SF + SMT received infusion of sufentanil 120 μg/kg via caudal vein 24 h before ischemia and then SMT 10 mg/kg was injected 10 min before ischemia. In group SMT, SMT 10 mg/kg was injected 10min before ischemia. MAP and HR were recorded at 30 min before ischemia, at 30 min of ischemia and at the end of reperfusion. The rate-pressure product (RPP) was calculated. Arterial blood samples were obtained immediately at the end of reperfusion to determine the plasma concentration of NO. Then the animals were sacrificed and myo cardial tissues were obtained to determine the area at risk (AAR), infarct size (IS) and iNOS expression. IS/AAR was calculated. Results Compared with group S, MAP and RPP were significantly decreased, while IS/AAR was significantly increased at 120 min of reperfusion in the other four groups, and MAP and RPP were significantly decreased at 30 min of ischemia in I/R and SMT groups ( P ＜ 0.05). Compared with group I/R, no significant change was found in HR, MAP and RPP in SF, SF + SMT and SMT groups, and in IS/AAR and plasma NO concentrations in SF + SMT and SMT groups ( P ＞ 0.05), but IS/AAR was significantly decreased, and the plasma NO concentration and iNOS expression were significantly increased in group SF ( P ＜ 0. 05). Conclusion iNOS is involved in reduction of myocardial I/R injury by sufentanil preconditioning in rats.
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Objective To investigate the effect of preoperative pravastatin preconditioning on myocardial ischemia-repedusion(I／R)injury in patients undergoing cardiac valve replacement with cardiopulmonary bypass (CPB).Methods Sixty ASA Ⅱ orⅢpatients of both sexes aged 18-64 yr undergoing cardiac valve replacement under CPB were randomly divided into 4 groups(n=15 each)：control group(group C)and 3 pravastatin groups receiving oral pravastatin 10，20 and 40 mg respectively every night for 7 days before operation(group P1-3).The number of patients receiving dopamine(≥5 μg·kg-1·min-1)and adrenaline was recorded from the termination of CPB to the end of operation，from the end of operation to 12 h after operation，during 12-24 h after operation and during 24-48 h after operation.Venous blood samples were taken from central venous line for measurement of plasme cTnI and CK-MB concentrations at 7 days before operation，before induction of anesthesia，at opening of the aorta and at 2，24 and 48 h after opening of aorta.Results The number of patients receiving dopamine and adrenaline was significantly less in group P3 than in group C(P<0.05).Plasma CK-MB and cTnI concentrations were significantly lower in group P3 than in group C(P<0.05).Conclusion Preconditioning with oral pravastatin(40mg／d for 7 consecutive days)can protect myocardium against I／R injury in patients undergoing cardiac valve replacement with CPB.
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Objective: To study the effect of ischemic preconditioning on heat-shock protein 70 (HSP70) expression and the learning,memory functions after forebrain ischemia-reperfusion injury in gerbils. Methods: Gerbils (n=100) were evenly randomized into four groups: Sham group, ischemia-reperfusion (I/R) group, ischemia preconditioning (IP) group, and Cycloheximide + IP group (Cycloheximide was administered 30 min before IP). Transient forebrain ischemia-reperfusion model was established by bilateral common carotid artery occlusion according to the method described previously, and ischemia preconditioning model was established as described by Kitagawa. Changes of neuron morphous in hippocampus CA1 region were observed by H-E staining 1, 2, and 3 days after reperfusion. The expression of HSP70 was examined by immunohistochemistry and Western blotting assay. Neuron apoptosis was detected by TUNEL method. The learning/memory functions of gerbils were examined using 4-PTT dry path maze 3, 4, 5, 6, and 7 days after reperfusion. Results: Compared with Sham group, I/R group had significantly decreased survival neurons(P<0. 05), increased neuron apoptosis(P<0. 05), increased expression of HSP70 (P<0. 05), and decreased learning/memory functions(P<0. 05). Compared with I/R group, IP group had significantly increased survival neurons(P<0. 05), decreased neuron apoptosis (P<0. 05), and increased expression of HSP70 (P<0. 05), and improved learning/memory functions (P < 0. 05). However, cycloheximide almost totally abolished the effect of ischemia preconditioning, with the neuron morphology, density, apoptosis, HSP70 expression, and learning/memory functions similar to those of I/R group. Conclusion: Ischemic preconditioning can protect against cerebral ischemia injury and improve the learning/ memory functions after forebrain ischemia-reperfusion damage, which is possibly through promoting HSP70 expression and starting endogenous neuroprotective mechanism, subsequently reinforcing the protective effect against ischemia.
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Objective To study the effect of preconditioning hyperbaric oxygenation on skin flap is-ehaemia tolerance. Methods 18 male SD rats were divided into the control and HBO preconditioning groups. In control group, an extended epigastrie adipocutaneous flap was raised, based on the right su-perficial epigastric artery and vein. 3-hours flap ischemia was induced by clamping the pedicle vessels with microvascular clamp. At the end of ischemia induction, the clamp was removed and the flap was sutured back. Rats in HBO preconditioning group were treated with HBO two days before operation. Flap surger-y began 1 hour after the last HBO treatment. The operation was the same as the control group. On the fifth postoperative day, the condition of the flap was recorded with transparent paper. Mean flap necrosis area was calculated with Acrobat software. Data were analyzed with SPSS software. Results The aver-age designed flap area was (51.59±6.62)cm2 and (52.71±2.05)cm2 in the control group and the HBO preconditioning group. The average flap survival area was (7.38±2.49)cm2 and (15.82±5.95)cm2. The difference was significant between the control and HBO preconditioning groups (t= 4. 14, P<0.01) in average flap survival area. Conclusion HBO preconditioning can rise flap ischaemia tolerance and enhance flap survival.
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@#Objective To explore initially the role of p38 mitogen activated protein kinases(p38 MAPK) in cerebral ischemic preconditioning.Methods Healthy adult SD rats were randomly divided into 5 groups: normal control group,sham-operated group,ischemia preconditioning or ischemia tolerance group,peripheral noxious control group,peripheral noxious tolerance group.SDS-PAGE,Western blot and Gel Doc imagine systems were applied to determine the p38 MAPK phosphorylation and protein expression in somatosensory cortex and hippocampus of rat.Results No significant changes of p38 MAPK in phosphorylation level and protein expression were found both in somatosensory cortex and hippocampus after ischemia preconditioning(P>0.05,n=6).Conclusion The development of cerebral ischemia preconditioning of rat might be not involved the phosphorylation and protein expression of p38 MAPK.
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Objective To investigate effects of cerebral isehemic preconditioning on neurological function,in- farct volume,and the expression of caspase-3 in brain issue after brain ischemia again,and to investigate the brain protection mechanism produced by cerebral ischemia preconditioning.Methods 48 healthy male Sprague-Dawley (SD)rats(weighted 200～250g)were randomly divided into 2 groups:ischemia group(n=24),ischemia precondi- tioning group(namely preconditioning group,n=24).Each group was divided into 4 subgroups according to 6h,1d, 2d,4d after ischemia again.Results At the same point of time after ischemia,neurological deficit in preconditioning group was much less than that in ischemia group,the difference was significant(P
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Objective:To discuss the protective effect of intestinal ischemic preconditioning(iIPC) on the myocardium and the role of uncoupling protein 2(UCP2) in myocardium with iIPC. Methods: The animal model was built by superior mesenteric artery ligation of rats.Then they were subjected to a sustained coronary occlusion of 30 min and reperfusion of 180 min.We evaluated the degree of the myocardial damage and used RT-PCR method to check the relative content of UCP2 mRNA.The IR control group underwent the coronary occlusion/ reperfusion with no intestinal ischemia and the blank group was sham-operated. Results:①Compared to the blank group,the IR control group showed much heavier damage in the ultramicro structure.And for the iIPC group, the damage in the ultramicro structure 0 h and 24 h after iIPC was lighter than that of the IR control group.②Compared to the expression of the UCP2 mRNA in the myocardium of rats in the IR control group,the expressions of iIPC 0 h,6 h,12 h,24 h,48 h groups increased substantially(P
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Aim To investigate a possible role for nitric oxide and neurogenic pathway in the protective effect of the limb preconditioning on the ischemic-reperfusion myocardium.Methods 64 Wistar rats were randomly divided into one of the four experimental groups.In Group Ⅰ,the rats underwent 30 min occlusion of the left anterior descending coronary artery,and 120 min reperfusion.In Group PL,the rats underwent four cycles of 5 min occlusion and reperfusion of both hind limbs using a tourniquet before the experiment was continued as in Group Ⅰ.In Group PL-N and Group PL-H,rats were administered with L-Nitro-Arginine Methyl Ester(L-NAME)10 mg?kg-1 or hexamethonium chloride 20 mg?kg-1,intravenously,20 min before IPC.Infarct size,as a percentage of the area at risk,was determined by triphenyltetrazolium chloride staining.And other 8 rats in each group,at the end of the experiment,all rats were killed and myocardium were stored in liquid nitrogen for the measurement of NO,NOS,iNOS and iNOS mRNA.Results The myocardial infarct size(IS)was decreased significantly in Group PL and Group PL-H compared with Group Ⅰ(P
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Objective This study evaluated whether liver ischemic preconditioning has delayed protective effect on liver ischemia-reperfusion injury and probe into the protective mechanism.Methods 36 wistar rats were randomly divided into two groups, group A:ischemic preconditioning,Group B:Control. The group A rats were subjected to liver ischemic preconditioning,While group B rats were subjected only laparotomy.After 48 hours,Liver tissue samples were abstained to detect the expression of HSP70.Occlusion the inflow vessels to the left and median lobes 45-minute then reperfuse 90-minute.Liver tissue samples were abstained to detect the expression of TNF-?.Serum ALT was detected before ischemia and after 90-minute reperfusion.Results The serum ALT level in group A is much lower than that in group B (P
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Objective To determine the difference between sevoflurane- and anoxic preconditioning in protecting newborn rat heart muscle cells from anoxia-reoxygenation injury. Methods The second generation of primary cultured cardiac myocytes from 2-3d newborn SD rats were randomly divided into 4 groups: control group (C), anoxia/reoxygenation group (A/R) in which cultured cardiac myocytes were exposed to 2h anoxia followed by 48h reoxygenation; anoxic preconditioning group (IP) in which before A/ R the cardiac myocytes were pretreated with 20 min anoxia; sevoflurane preconditioning group (S) in which cardiac myocytes were pretreated with 20 min 2.5% sevoflurane (1.5 MAC) before A/R. Ultrastructure of heart muscles cells was observed 1 h after reoxygenation, Cell survival was determined by MTT rapid colorimetric assay and apoptosis was measured by flow cytometry at 0, 1, 12, 24, 36 and 48 h after reoxygenation. Results (1) In S and IP group there was no significant change in ultrastructure and no apoptosis cell was found, whereas in A/R group the change in ultrastructure was significant , and apoptosis cells were found. (2) The cell survival in group S and group IP was significantly lower than that in group C but significantly higher than that in group A/R. (P 0.05) . The survival of cardiac myocytes increased with prolongation of reoxygenation time in group S and group IP. (3) The apoptosis percentage of cells in group S and group IP was significantly higher than that in group C and lower than that in group A/R(F
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Objective To investigate the relation between the expression of Bcl-2 protein and protection against ischemic neuronal damage by preconditioning with sublethal ischemia .Methods The cerebral ischemia was induced by occlusion of bilateral common carotid arteries .Sixty-three gerbils were divided randomly into four groups:sham operative control group (group A,n=5),ischemic preconditioning control group (group B ;n=6) with a single 2-min cerebral ischemia; ischemia preconditioning group (group PC,n=26) and ischemic control group (group IR,n=26) with 5-min ischemia being induced following 3 days of reperfusion with or without 2-min ischemic preconditioning,then with reperfusion lasting 4 hours (group PC1,n=5;group IR1,n=5),24 hours (group PC2,n=7;group IR2,n=7),72 hours (group PC3,n=7;group IR3,n=7)or 7 days (group PC4,n=7;group IR4 ,n=7) respectively.Paraffin sections of hippocampus were used for Bcl-2 protein immunohistochemical staining.Results In group B,Bcl-2 protein immunoreactivity (the intensity of staining) significantly increased as compared with that in group A(P