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Objective:To evaluate the effect of sevoflurane postconditioning on early inflammatory responses during intestinal ischemia-reperfusion (I/R) in rats.Methods:Sixty clean-grade Sprague-Dawley rats, aged 8-10 weeks, weighing 200-230 g, were divided into 3 groups ( n=20 each) using a random number table method: sham operation group (Sham group), intestinal I/R group (I/R group), and sevoflurane postconditioning group (Sevo group). Intestinal I/R was produced by occlusion of the superior mesenteric artery for 60 min followed by reperfusion for 2 h in anesthetized rats in I/R group and Sevo group.Laparotomy was performed, and the superior mesenteric artery was only isolated in Sham group.The rats inhaled 1.15% sevoflurane for 30 min for postconditioning in Sevo group.Blood samples were collected by cardiac puncture at 2 h of reperfusion, and then the rats were sacrificed.Samples of intestine were obtained for examination of the pathological changes of intestinal tissues (with a light microscope) which were scored according to Chiu and for determination of the neutrophil L-selectin levels in blood (by flow cytometry), tumor necrosis factor-alpha (TNF-a) expression (by Western blot), myeloperoxidase (MPO) activity (by spectrophotometry). Results:Compared with group Sham, the neutropil L-selectin level in blood was significantly increased in group I/R and decreased in group Sevo, and Chiu′s score, TNF-a expression and MPO activity were significantly increased in I/R and Sevo groups ( P<0.05). Compared with group I/R, the neutropil L-selectin level in blood, Chiu′s score, TNF-a expression, TNF-a expression and MPO activity were significantly decreased ( P<0.05), and the pathological changes were significantly attenuated in group Sevo. Conclusion:The mechanism by which sevoflurane postconditioning reduces intestinal I/R injury may be related to inhibiting early inflammatory responses in rats.
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Objective:To investigate whether ventricular non-excitatory electrical stimulation(NES)preconditioning can protect myocardial ischemia-reperfusion(IR)injury in aged mice by regulating cardiac calcitonin gene-related peptide(CGRP).Methods:Male C57BL/6J mice were randomly divided into 3 groups, (1)the Sham group, receiving sham operation group(n=6); (2)the IR group, receiving ligation of coronary artery to induce myocardial ischemia for 45 min and reperfusion for 120 min(n=13); (3)the NES group, IR model receiving NES from 15 min before IR to the end of reperfusion(n=13). Infarct size was detected by staining with 2, 3, 5-triphenyltetrazolium chloride.The level of serum cTnI and expression of myocardial CGRP were measured by enzyme linked immunosorbent assay and quantitative real time polymerase chain reaction.Results:Compared with the IR group, the infarct sizes were significantly lower in NES group[(38.17±4.36)% vs.(45.33±5.68)%, P<0.05]. Besides, the IR and NES groups were associated with significantly increased levels of serum cTnI[(10.89±2.14)μg/L, (7.03±1.79)μg/L vs.(3.92±0.47)μg/L, P<0.001], myocardial CGRP protein[(26.33±4.55)μg/kg, (19.67±5.79)μg/kg vs.(17.00±2.90)μg/kg, P<0.01], CGRP mRNA[(1.40±0.20), (2.20±0.75) vs.(1.05±0.10), P<0.01]compared with the Sham group.Furthermore, the NES group was associated with markedly decreased levels of serum cTnI and myocardial CGRP protein, and increased level of CGRP mRNA compared with the IR group(all P<0.05). Conclusion:NES may protect myocardium IR injury by regulating endogenous CGRP expression in aged mice.
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Objective To investigate the protective effects of pretreatment with a Shenfu(SF) injection on arrhythmias induced by myocardial ischemia-reperfusion(IR)injury in aged mice.Methods Thirty 18-month-old C57BL/6J mice were randomly divided into 3 groups (n=10,each group):the sham treatment group(receiving sham operation without thoracotomy),the IR group (undergoing the ligation of the left anterior descending coronary artery with ischemia for 30 min and reperfusion for 2 h)and the SF group(receiving SF intraperitoneal injection of 10 ml/kg 30 min before thoracotomy and the same treatment as the IR group).Arrhythmias were monitored,and serum levels of creatine kinase-isoenzyme (CK-MB),troponin (cTnI) and tumor necrosis factor α (TNFα),and the ratio of myocardial connexin 43 (Cx43) phosphorylation (ser368) to total protein (p-Cx43/t-Cx43) were detected in the three groups.Results Ventricular arrhythmias occurred in the IR and SF groups.Compared with the IR group,ventricular arrhythmias in the SF group were alleviated,the frequency of ventricular premature systolic episodes was reduced(36.6 ± 13.5 times vs.48.4 ± 22.1 times),the frequency of ventricular tachycardia/fibrillation decreased(3.4 ± 1.8 times vs.7.6 ± 3.5 times),and the total duration of ventricular tachycardia/fibrillation episodes was shortened(8.9± 4.5 times vs.17.7± 5.1 times)in the SF group(P＜0.05),but there was no significant difference in arrhythmia scores(1.8± 1.2 points vs.1.9 ± 1.7 points,P ＞0.05) between the two groups.Compared with the sham treatment group,serum levels of CK-MB,cTnI and myocardial TNF(increased in the IR and SF groups (P ＜ 0.05),and their levels were lower in the SF group than in the IR group (P＜0.05).Compared with the sham treatment group,the ratio of Cx43 ser368/total protein was lower in the IR and SF groups,but was higher in the SF group than in the IR group(P＜0.05).Conclusions SF pretreatment can significantly reduce IR-induced arrhythmias in aged mice possibly by reducing TNF(and up-regulating the phosphorylation activity of Cx43.
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Objective@#To investigate the protective effects of pretreatment with a Shenfu(SF)injection on arrhythmias induced by myocardial ischemia-reperfusion(IR)injury in aged mice.@*Methods@#Thirty 18-month-old C57BL/6J mice were randomly divided into 3 groups(n=10, each group): the sham treatment group(receiving sham operation without thoracotomy), the IR group(undergoing the ligation of the left anterior descending coronary artery with ischemia for 30 min and reperfusion for 2 h)and the SF group(receiving SF intraperitoneal injection of 10 ml/kg 30 min before thoracotomy and the same treatment as the IR group). Arrhythmias were monitored, and serum levels of creatine kinase-isoenzyme(CK-MB), troponin(cTnI)and tumor necrosis factor α(TNFα), and the ratio of myocardial connexin 43(Cx43)phosphorylation(ser368)to total protein(p-Cx43/t-Cx43)were detected in the three groups.@*Results@#Ventricular arrhythmias occurred in the IR and SF groups.Compared with the IR group, ventricular arrhythmias in the SF group were alleviated, the frequency of ventricular premature systolic episodes was reduced(36.6±13.5 times vs. 48.4±22.1 times), the frequency of ventricular tachycardia/fibrillation decreased(3.4±1.8 times vs. 7.6±3.5 times), and the total duration of ventricular tachycardia/fibrillation episodes was shortened(8.9±4.5 times vs. 17.7±5.1 times)in the SF group(P<0.05), but there was no significant difference in arrhythmia scores(1.8±1.2 points vs. 1.9±1.7 points, P>0.05)between the two groups.Compared with the sham treatment group, serum levels of CK-MB, cTnI and myocardial TNF(increased in the IR and SF groups(P<0.05), and their levels were lower in the SF group than in the IR group(P<0.05). Compared with the sham treatment group, the ratio of Cx43 ser368/total protein was lower in the IR and SF groups, but was higher in the SF group than in the IR group(P<0.05).@*Conclusions@#SF pretreatment can significantly reduce IR-induced arrhythmias in aged mice possibly by reducing TNF(and up-regulating the phosphorylation activity of Cx43.
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Objective@#To evaluate the effects of ketamine anesthesia on proteome in hippocampus in aged rats.@*Methods@#Thirty healthy male Wistar rats, aged 20 months, weighing 560-610 g, were divided into 2 groups (n=15 each) using a random number table method: control group (group C) and ketamine group (group K). In group K, ketamine 80 mg/kg was intraperitoneally injected, additional 1/2 initial dose was given when the righting reflex was recovered, and anesthesia was maintained for 3 h. Morris water maze test was performed starting from 1st day after the end of anesthesia.Five rats were selected at days 1 and 7 after the end of anesthesia and sacrificed, and hippocampal tissues were obtained to extract proteins.Proteins extracted from rat hippocampi were identified by 2-dimensional electrophoresis (2-DE). The differentially expressed proteins were analyzed by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF-MS) and biological information system.@*Results@#Compared with group C, the escape latency and total swimming distance to find the submerged platform in Morris water maze at the 1st day after anesthesia were significantly prolonged in group K (P<0.05 or 0.01). The MALDI-TOF-MS analysis showed that there were 21 differentially expressed proteins at 1st day after ketamine anesthesia, of which 6 proteins (involving maintenance of intracellular protein homeostasis, energy metabolism, etc.) presented with up-regulated expression and 15 proteins (involving synaptic vesicle transport efficiency, synaptic structural and functional plasticity, maintenance of intracellular protein homeostasis, NMDA-mediated Ca2+ signal transport, energy metabolism, etc.) presented with down-regulated expression.There were 8 differentially expressed proteins at 7th day, including 3 proteins with up-regulated expression and 5 proteins with down-regulated expression (P<0.05).@*Conclusion@#Ketamine anesthesia can induce 21 differentially expressed proteins in hippocampi of aged rats, involving synaptic vesicle transport efficiency, synaptic structural and functional plasticity, intracellular protein homeostasis, NMDA-mediated Ca2+ signal transport, energy metabolism, and etc.which may be involved in the mechanism of ketamine-induced temporary cognitive dysfunction.
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Objective To evaluate the effects of ketamine anesthesia on proteome in hippocampus in aged rats.Methods Thirty healthy male Wistar rats,aged 20 months,weighing 560-610 g,were di-vided into 2 groups(n＝15 each)using a random number table method: control group(group C)and ket-amine group(group K).In group K,ketamine 80 mg/kg was intraperitoneally injected,additional 1/2 ini-tial dose was given when the righting reflex was recovered,and anesthesia was maintained for 3 h.Morris water maze test was performed starting from 1st day after the end of anesthesia.Five rats were selected at days 1 and 7 after the end of anesthesia and sacrificed,and hippocampal tissues were obtained to extract proteins.Proteins extracted from rat hippocampi were identified by 2-dimensional electrophoresis(2-DE).The differentially expressed proteins were analyzed by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry(MALDI-TOF-MS)and biological information system.Results Compared with group C,the escape latency and total swimming distance to find the submerged platform in Morris water maze at the 1st day after anesthesia were significantly prolonged in group K(P＜0.05 or 0.01).The MAL-DI-TOF-MS analysis showed that there were 21 differentially expressed proteins at 1st day after ketamine an-esthesia,of which 6 proteins(involving maintenance of intracellular protein homeostasis,energy metabo-lism,etc.)presented with up-regulated expression and 15 proteins(involving synaptic vesicle transport ef-ficiency,synaptic structural and functional plasticity,maintenance of intracellular protein homeostasis,NMDA-mediated Ca2+signal transport,energy metabolism,etc.)presented with down-regulated expres-sion.There were 8 differentially expressed proteins at 7th day,including 3 proteins with up-regulated ex-pression and 5 proteins with down-regulated expression(P＜0.05).Conclusion Ketamine anesthesia can induce 21 differentially expressed proteins in hippocampi of aged rats,involving synaptic vesicle transport efficiency,synaptic structural and functional plasticity,intracellular protein homeostasis,NMDA-mediated Ca2+signal transport,energy metabolism,and etc.which may be involved in the mechanism of ketamine-induced temporary cognitive dysfunction.
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Objective To evaluate the role of transient receptor potential vanillic acid subtype 1 (TRPV1)/calcitonin gene-related peptide (CGRP) signaling pathway in lidocaine postconditioning-induced reduction of myocardial ischemia-reperfusion (I/R) injury in rats.Methods Forty healthy male SpragueDawley rats,aged 3 months,weighing 250-300 g,were divided into 5 groups (n=8 each) using a random number table method:sham operation group (group Sham),group I/R,lidocaine postconditioning group (group LP),lidocaine postconditioning plus CGRP8-37 group (group LP+CGRP8-37),and lidocaine postconditioning plus capsazepine group (group LP+Capz).Myocardial ischemia was induced by ligating the anterior descending branch of left coronary artery for 30 min,followed by 120-min repeRFusion in anesthetized rats.Lidocaine 2 mg/kg was injected via the tail vein at 5 min before reperfusion in group LP.In group LP + CGRP8-37,lidocaine was intravenously injected,and CGRP receptor selective antagonist CGRP8-37 2 mg/kg was intravenously injected at the same time.In group LP+Capz,lidocaine was injected intravenously,and TRPV1 blocker capsazepine 3 mg/kg was injected intravenously at the same time.A catheter was retrogradely implanted to the left ventricle,and heart rate (HR),left ventricular systolic pressure (LVSP),left ventricular end-diastolic pressure (LVEDP),and the maximum rate of increase or decrease in left ventricular pressure (±dp/dtmax) were continuously monitored and recorded.Blood samples were collected from the carotid artery at 120 min of reperfusion for determination of cardiac troponin I (cTnI),myoglobin (Myo) and creatine kinase-MB (CK-MB) concentrations in serum.Rats were then sacrificed for determination of myocardial infarct size.Results Compared with Sham group,the serum concentrations of cTnI,Myo and CK-MB were significantly increased,LVSP,+dP/dtmax and HR were decreased,and LVEDP and-dP/dtmax were increased in I/R group and LP group (P＜0.05).Compared with group I/R,the serum concentrations of cTnI,Myo and CK-MB and myocardial infarct size were significantly decreased,LVSP and +dP/dtmax were increased,and LVEDP,-dP/dtmax and HR were decreased in group LP (P＜0.05),and no significant change was found in the parameters mentioned above in group LP+ CGRP8-37 and group LP+Capz (P＞0.05).Compared with group LP,the serum concentrations of cTnI and Myo,myocardial infarct size and LVEDP were significantly increased,and + dP/dtmax was decreased in group LP+CGRP8-37,and the serum concentrations of cTnI and Myo and myocardial infarct size were significantly increased,LVSP and +dP/dtmax were decreased,and LVEDP was increased in group I/R+Lido+Capz (P＜0.05).Conclusion The mechanism by which lidocaine postconditioning mitigates myocardial I/R injury is related to activating TRPV1/CGRP signaling pathway in rats.