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Abstract Introduction: Reperfusion injury leads to systemic morphological and functional pathological alterations. Some techniques are already estabilished to attenuate the damage induced by reperfusion. Ischemic preconditioning is one of the standard procedures. In the last 20 years, several experimental trials demonstrated that the ischemic postconditioning presents similar effectiveness. Recently experimental trials demonstrated that statins could be used as pharmacological preconditioning. Methods: 41 Wistar rats (Rattus norvegicus albinus) were distributed in 5 groups: Ischemia and Reperfusion (A), Ischemic Postconditioning (B), Statin (C), Ischemic Postconditioning + Statins (D) and SHAM (E). After euthanasia, lungs, liver, kidneys and ileum were resected and submitted to histopathological analysis. Results: The average of lung parenchymal injury was A=3.6, B=1.6, C=1.2, D=1.2, E=1 (P=0.0029). The average of liver parenchymal injury was A=3, B=1.5, C=1.2, D=1.2, E = 0 (P<0.0001). The average of renal parenchymal injury was A=4, B=2.44, C=1.22, D=1.11, E=1 (P<0.0001). The average of intestinal parenchymal injury was A=2, B=0.66, C=0, D=0, E=0 (P=0.0006). The results were submitted to statistics applying Kruskal-Wallis test, estabilishing level of significance P<0.05. Conclusion: Groups submitted to ischemic postconditioning, to pre-treatment with statins and both methods associated demonstrated less remote reperfusion injuries, compared to the group submitted to ischemia and reperfusion without protection.
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Animals , Male , Rats , Reperfusion Injury/prevention & control , Ischemic Preconditioning/methods , Ischemic Postconditioning/methods , Atorvastatin/therapeutic use , Rats, Wistar , Disease Models, AnimalABSTRACT
Objectives To investigate the effect of electric vagal stimulation on the gene expression of injured myocardium from ischemia/reperfusion rat model and explore the involved molecular mechanism.Methods Twenty Sprague Dawley male rats were randomly selected and divided into 2 groups evenly:ischemia/reperfusion group (I/R group),and vagus nerve stimulation group (STM group).The left anterior descending coronary artery (LAD) was ligated and subjected to 30 min of myocardial ischemia followed by 2 h of reperfusion.In addition,10 min before reperfusion,left cervical vagus nerve of STM group was subjected to electronic stimulation at 5 V,2 ms and 1 Hz for 20 min.After 120 min of reperfusion,every group was randomly divided into two parts.One part that myocardium was collected from left ventricle was applied to determine the area of myocardial infarction.The RNA isolated from another part of the ischemic myocardium collected from left ventricle was hybridized to get gene expression profiles and the quality of hybridized RNA from both I/R and STM group was assessed and analyzed.GeneSpring software was applied to screen out the genes,which show significant difference between groups I/R and STM.Real-time polymerase chain reaction (RT-PCR) was applied to analyze the expression of important genes.Results (1)The area of myocardial infarction of STM (25.5 ± 3.9) ％ was significant reduced relative to L/R group (45.5 ± 4.8) ％ (P ＜ 0.05).(2)The expression levels of 186 genes were changed significantly,and analyzed by Gene ontology (GO) software,there were 3 kinds of genes were affected.The upregulated genes were reported to show protective effect on myocardium.The downregulated gene was relative to inflammation.(3)The RT-PCR result confirmed the genechip assay.Conclusions Electric vagal stimulation can reduce myocardial I/R injury in rats.Significant change of the gene expression was detected between groups I/R and STM.The results suggest that activation of cholinergic anti-inflammatory pathway be involved in the mechanism.
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Objeetive To investigate protective effect of trimetazidine on myocardial ischemia/reperfusion injury (MIRI) in rats.Methods Forty Wistar rats were randomly divided into MIRI group (n =10 rats),trimetazidine high-dosage group (n =10 rats; 20 mg/kg),trimetazidine low-dosage group (n=10 rats; 10 mg/kg),and the normal control group (n =10 rats).After MIRI,hemodynamic changes were observed,the concentration of IL-6 and TNF-α was determined,and the cardiac muscle histology under the microscope was observed.Results Hemodynamic studies:Compared to the indices LVSP(198 ±35.5) mmHg,LVEDP (17 ±9.18) mmHg,+ dp/dt max (11050 ± 1517.4) mmHg/s,and-dp/dtmax (9175± 1900) mmHg/s] in the sham-operated group,the indices [LVSP (143 ± 24.5) mmHg,LVEDP (37.5 ±7.16)mmHg,+ dp/dtmax (7450 ± 1755.1) mmHg/s,and-dp/dtmax (6075 ± 1641) Hg/S] in the MIRI group,the indices [LVSP (154.5 ± 31.1) mmHg,LVEDP (31.3 ± 12.6) mmHg,± dp/dtmax (8527.7 ±2251.5) mmHg/s,and-dp/dtmax (6694 ± 2242.2) mmHg/s] in the trimetazidine low-dosage (10 mg/kg)group,the indices[LVSP (168.3 ± 17.6) mmHg,LVEDP (28 ± 10.05) mmHg,+ dp/dtmax (9213.6 ±1747) mmHg/s,and-dp/dtmax (7568 ± 1462.4) mmHg/s] in the trimetazidine high-dosage (20 mg/kg)group,left ventricular remodeling end diastolic pressure (LVEDP),left ventricular systolic pressure (LVSP),and left ventricular pressure maxial rate of rise and fall (± dp/dtmax) were significantly decreased.Compared to the MIRI group,LVSP and ± dp/dtmax in the trimetazidine high-dosage (20 mg/kg)group were significantly increased (P ＜ 0.01),and myocardial damage of MIRI group was more severe in microscope.Compared to the sham-operated group [IL-6 (2556.5 ± 662.9) ng/ml,and TNF-α (134 ± 73.7)ng/ml],the corresponding indices [IL-6 (3664.0 ± 995.7) ng/ml,and TNF-α (443 ± 22.1) ng/ml] in the MIRI group,[IL-6 (3692.8 1545.2) ng/ml,and TNF-α (295 ± 24.2) ng/ml] in the trimetazidiue low-dosage (10 mg/kg) group,and[IL-6(2654.8 ±681.7) ng/ml,and TNF-α(230 ±7.8) ng/ml]in the trimetazidine high-dosage (20 mg/kg) group,the levels of IL-6 and TNF-α were significantly increased.Compared to the MIRI group,the levels of IL-6 and TNF-α were significantly decreased in the trimetazidine high-dosage (20 mg/kg) group (P ＜ 0.01).Conclusions The high-dosage (20 mg/kg) of trimetazidine had a protective effect on myocardial ischemia-reperfusion injury.
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Objective To investigate the effects of L-carnitine on myocardial enzymes in infants with congenital heart disease undergoing open cardiac operation with cardio pulmonary bypass (CPB).Methods From Mar.2011 to Nov.2012,there were 60 infants with ventricular septal defects,whom were divided randomly into the test (n =30) and control (n =30) groups.L-carnitine was put in the cold crystal cardiac arresting liquid in the test group (6 g/L),other experimental conditions were the same between two groups.Before CPB,at 1 h,24 h,7 d after the pump-off,venous blood was drawn to test the level of serum creatine kinase (CK),CK-MB isozyme,cardiac Troponin I (cTnI).Blood samples were taken at different time points for the analysis of tlymphocyte and its subtype by flow cytometry.Observing the dopamine and other vasoactive drug 8 hours and 24 hours after the pump-off,using data obtained from the t-test done statistically.Results The levels of CK and CK-MB and cTnI had no difference between two groups before operation.From the end of CPB,the levels of CK and CK-MB and cTnI were significantly lower in the test group than that in the control group (P ＜0.05).The automatic jump higher rate (95％ vs 70％,P ＜ 0.05) and the amount of dopamine were significantly less than the control group (P ＜ 0.05).Conclusions L-carnitine improved obviously microcirculation of ischemic cardiac reperfusion injury undergoing open cardiac operation under CPB and heart function.It had a good protective effect on myocardium in infants.
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Objective To investigate the expression of C/EBP homology protein(CHOP) in rat brain tissue after focal cerebral ischemia-reperfusion,as well as to observe the influence of the shenxiong injection on the expression of CHOP.Methods One hundred forty four male rats were randomly divided into three groups:the sham-operation group,operation group,shenxiong group.Focal cerebral ischemia and reperfusion rat models were established by using suture.Zea Longa method was introduced to evaluate neurologic behavioral changes.The levels of mRNA and protein of CHOP were measured with methods of immunohistochemistry and reverse transcription polymerase chain reaction.The neuronal apoptosis was detected by the method of terminal deoxynucleotidy1 transferase-mediated dUTP-biotin nick end labeling.Results The expression of CHOP was up-regulated in per-infarction after cerebral ischemia-reperfusion in rats.CHOP mRNA and protein levels peaked at the 12th h and 24th h after reperfusion,respectively.The apoptosis cell counting increased gradually after cerebral ischemia-reperfusion and peaked at the 24th h after reperfusion.Compared with the saline control group,treatment with shenxiong injection could reduce the neuronal apoptosis at the 6th,12th,24th,and 72nd h after reperfusion (P ＜0.01).Compared with the saline control group,treatment with shenxiong injection could decrease CHOP mRNA and protein expression at the 6th,12th,24th,and 72nd h after reperfusion (P ＜0.01).Conclusions Shenxiong Injection may prevent neurocyte from apoptosis by inhibition of the expression of CHOP induced by endoplasmic reticulum stress.
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Objective To investigate the brain protective effect of isoflurane preconditioning on the rat liver against ischemia-reperfusion through determining the content of S-100β protein in peripheral blood in combination with mitochondrial ultrastructure in rat brain.Methods A total of 45 SD rats were randomly divided into three groups,sham group (group S):the only separation of the hepatoduodenal ligament,but did not block the hepatic portal blood supply; ischemia-reperfusion group (group I/R):liver ischemia 60min,reperfusion 120 min; isoflurane preconditioning group (group ISO):60 min before liver I/R,ISO pretreatment for 30 min,elution in the air after 30 min; 24 h after recirculation the forebrain tissues were rapidly removed.The changes of mitochondrial ultrastructure were observed by electron microscopy.The content of S-100β protein in serum was measured before ischemia and reperfusion 120 min through the application of Elisa kit.Results Marked swelling of mitochondria with disrupted cristae and damaged matrix were observed in group I/R,while relative intact mitochondria were seen in sham and ISO groups.The content of S-100β protein in serum was significantly higher in I/R group [(1.52 ±0.26) μg/ml] than in sham [(0.31 ±0.05)μg/ml] and ISO [(0.79 ± 0.21) μg/ml] groups (P ＜0.05).Conclusions The liver ischemia-reperfusion may injure the brain of the rat and isoflurane preconditioning can protect the rat brain from injury.