Effects of ischemic preconditioning on hepatocyte apoptosis induced by hepatic ischemia-reperfusion in cirrhotic rats

AIM:To investigate the protective effect of ischemic preconditioning (IPC) on hepatic ischemia-reperfusion(I/R) injury in cirrhotic rats and its possible mechanism. METHODS:Hepatic I/R was induced by Pringle maneuver. The cirrhotic rats were randomized into three groups: Group A: before 30 min of ischemia, a short period of 5 min ischemia and 5 min reperfusion were given; Group B: before 30 min of ischemia, a short period of 10 min ischemia and 10 min of reperfusion were given; Group C: 30 min ischemia only. The serum alanine transferase (ALT), hepatic Fas-mRNA, caspase-3 activity and hepatocyte apoptosis were analyzed. RESULTS:The 7-day survival rate in the group A and B were 100%, respectively. However, it was only 62.5% in the group C. After 6 h of reperfusion, the ALT levels in both group A and B were significantly lower than that of in group C, P＜0.01. The ALT level of group A was also lower than that of group B, P＜0.01. The hepatic Fas-mRNA expression, caspase-3 activity and apoptotic hepatocyte in group A were significantly lower than those of in group C, P＜0.01. CONCLUSIONS:IPC has significant protective effect against hepatic I/R injury. An IPC with 5 min of ischemia and 5 min of reperfusion has the maximal protective effect. The protective mechanism of IPC against hepatic I/R injury is via down-regulation of Fas-mRNA expression, inhibiting caspase-3 activity and subsequently inhibiting hepatocyte apoptosis.     

Protection of the limb ischemic preconditioning on the injury of gut is concerned with NO/ET-1 system in rats

AIM: To study the relationship between disturbance of nitric oxide/endothelin-1 (NO/ET-1) and the injury of gut following limb ischemia-reperfusion (I/R) in rats as well as the regulation of NO/ET-1 system by limb I/R preconditioning (IPC). METHODS: A limb ischemia-reperfusion injury model in rats was established. The animals were randomly divided into three groups: control group, IR group and IPC group. The contents of diamide oxidase(DAO), nitric oxide (NO), endothelin-1 (ET-1) and ratio of nitric oxide/endothelin-1 (NO/ET-1) in the plasma and the gut were measured. The leavels of myeloperoxidase, ratio of DNA chain (%), total nitric oxide synthase (tNOS), inducible nitric oxide synthase (iNOS) and constitutive nitric oxide synthase (cNOS) in the gut were determined. The expression of iNOS and endothelial NOS (eNOS) were detected by the immunohistochemical method. RESULTS: It was found that the levels of NO, ET-1 in the plasma and the gut tissue all increased after reperfusion, while the values of NO/ ET-1 decreased. The values of DAO in the plasma and MPO in the gut increased, while the contents of DAO and the ratio of DNA chain (%) in the gut decreased. The expression of iNOS elevated, cNOS (mainly eNOS) reduced and total NOS increased. The protection of the limb IPC attenuated the disturbance of NO/ET-1. CONCLUSION: The intestinal injury following limb I/R is related to the disturbance of NO/ET-1. The protection of the limb IPC might be conducted by its regulating NO/ET-1 system. The endothelial NOS increases and non-endothelial NOS decreases in this situation.     

Role of nitric oxide in ischemia/reperfusion injury and ischemic preconditioning

AIM: To clarify the role of nitric oxide(NO) in ischemic preconditioning(IP) and its effects on apoptosis. METHODS: Seventy-two male Wistar rats were divided into the following six groups:ischemia/reperfusion (IR) group,IP group,IR+L-arg group,IP+L-arg group,IR+L-NAME group and IP+L-NAME group,The following changes were measured:cardiac hemodynamic parameters,infarct size,PMNs counting myocardial MPO activity and TUNEL staining.RESULTS: ①L-arg significantly attenuated ischemia/reperfusion-induced heart injury,reduced PMNs infiltration and cardiomyocyte apoptosis.②L-NAME also significantly reduced infarct size,PMNs infiltration and cardiomyocyte apoptosis compared with IR group,however,L-NAME aggravated ischemia/reperfusions-induced cardiac functional injury.③L-arg or L-NAME did not significantly alter the protective effect of ischemic preconditioning. CONCLUSION: Increased production of endogenous NO before prolonged ischemic period can protect hearts and inhibit apoptosis.L-NAME can inhibit iNOS activity and ONOO^- production in reperfusion period to protect heart.     

Effects of Ca2+on the releases of ET-1, NO and PGI2 from bovine coronary artery endothelial cells during hypoxia

AIM: To explore the mechanism of ET-1, NO and PGI² release from coronary artery endothelial cells(CAEC) induced by acute hypoxia. METHODS: Bovine coronary artery endothelial cells were cultured and [⁴⁵ Ca²⁺] was used to investigate the difference of calcium uptake between normoxia group and hypoxia group(3% O₂). The contents of ET-1, NO and PGI² in media of normoxia group, hypoxia group and hypoxia + verapamil group were measured 24 h after hypoxia. RESULTS: [ ⁴⁵ Ca²⁺] uptake by CAEC in hypoxia group was 1.9 times more than normoxia group(P< 0.01). Hypoxia + verapamil group released more PGI², ET-1 and less NO than hypoxia group(P< 0.05). CONCLUSION: Changes of ET-1, NO and PGI² releases during hypoxia may be caused by the inflow of Ca²⁺ into coronary artery endothelial cells.     

The protective effect of preconditioning on rabbit liver during ischemia and reperfusion and its potential mechanism

AIM:To investigate the protective effect of preconditioning on rabbit liver during total ischemia and reperfusion and its mechanism. METHODS: Using hepatic ischemia and reperfusion injury (HIRI) model in rabbits, animals were randomly divided into three groups: control group (A), non-preconditioning group(B) and preconditioning group(C), different effects of preconditioning on several parameters including alanine aminotransferase (ALT) activity and levels of nitric oxide (NO) and malondialdehyde (MDA) in plasma or liver tissue as well as hepatocellular morphological changes were measured and observed during HIRI. RESULTS:In C group NO levels of plasma and liver tissue were higher than those in B group (P＜0.05);While MDA levels and ALT value in plasma were lower than those in B group (P＜0.05 and P＜0.01); and there were not significant differences between C and A group (P＞0.05); abnormal morphological chages of liver cells in A group were ameliorated remarkably too during HIRI. CONCLUSION:Preconditioning can attenuate HIRI by improving NO level and reducing oxygen free radicals level.     

Study on protective mechanism of non-wounded ischemic preconditioning on rat ischemia/reperfusion myocardium

AIM:To investigate probable protective mechanism of non-wounded legs ischemic preconditioning on ischemia/reperfusion(I/R) myocardium. METHODS: 36 male SD rats, weighting (250±30) g,were divided into 4 groups.They are normal control(NC);I/R; classical ischemic preconditioning(C-IPC)and non-wounded legs ischemic preconditioning(N-WIPC). NO in plasm,expression of myocardial HSP 70 mRNA, the activities of 5’-NT and CAT of myocardium were observed in all groups. RESULTS:The level of NO in plasm significantly enhanced in groups C-IPC and N-WIPC compared with that in groups I/R and NC ( P <0.01),expression of myocardial HSP 70 mRNA was greatly increased in both C-IPC and N-WIPC groups, the activities of 5’-NT, CAT of myocardium were also raised in groups C-IPC and N-WIPC ( P< 0.05 vs I/R),but there was no difference between C-IPC and N-WIPC( P >0.05). CONCLUSION:The possible protective mechanism involved in N-WIPC is similar to that in C-IPC, which is due to increase of endogenous myocardial protective substances.     

Nitric oxide opens the second window of protection in ischemic preconditioning via induction of heat shock protein 72

AIM:To examine the inhibition of nitric oxide (NO) synthesis during ischemic preconditioning (IP) on the induction of heat shock protein 72 (HSP72) and infarct size-limiting effect of the second window of protection. METHODS:Rabbits were subjected to 4 cycles of 5 min of coronary artery occlusion separated by 10 min reperfusion, or received a sham operation. During this procedure, N^G-nitro-L-arginine methyl ester (L-NAME, an inhibitor of NO synthase) was injected intravenously 5 min before IP followed by its continuous infusion. Twenty-four hours later, the hearts were rapidly excised for assaying HSP72 expression or were subjected to 30 min coronary artery occlusion followed by 120 min reperfusion and then measured infarct size (IS). RESULTS:Twenty-four hours later, immunoblotting revealed an increase in HSP72 protein levels in the IP group, and this was blocked by L-NAME. IS of the IP rabbits was reduced as compared with the control (29.8%±3.7% vs 50.8%±4.3%, P＜0.01). IS in the IP rabbits was elevtated as a result of L-NAME treatment (46.0%±5.1%). Administration of L-arginine reversed the effects of L-NAME on the induction of HSP72 and IS (33.5%±4.0%). The intravenous administration of S-nitroso-N-acetylpenicillamine (SNAP, a NO donor) increased the induction of HSP72 and reduced IS (31.3%±5.7%, P＜0.01vs control) 24 h later. CONCLUSION:These findings suggest that NO may be involved in the induction of HSP72 and the opening of the second window of protection of IP.     

Production of nitric oxide and change of nitric oxide synthase activity in brains mitochondria of the rats with focal cerebral ischemia/reperfusion

AIM and METHOD:To determine the production of nitric oxide(NO) and change of NO synthase(NOS) activity in mitochondria isolated from the rat brains of the ischemia/reperfusion rat model produced by transient occlusion of middle cerebral artery on the following time points:2 h after occlusion of artery and 30 min,2 h, 4h after reperfusion.RESULTS:After the occlusion of middle cerebral artery,the respiratory control rate(RCR) of mitochondria significantly decreased and slightly increased at 4h after reperfusion.Meantime,the production of NO in mitochondria increased significantly.But with the increase of perfusion, production of NO gradually decreased and reached normal level as in the control group.It also shows that cerebral ischemia increased NOS's activity significantly in the mitochondria and still kept a higher level than the control group although it decreased gradually after reperfusion.But the iNOS's activity did not show obvious change.The change of total NOS's activity depends on the change of cNOS's activity.CONCLUSION: The activation of NO/NOS system in the mitochondria might play an important role in the reperfusion injury during reperfusion of ischemic brain.     

Effects of maternal limb ischemic preconditioning on fetal hippocampal neuron apoptosis induced by intrauterine distress-reoxygenation in rats

AIM: To evaluate the influence of maternal limb ischemic preconditioning (LIP) on the apoptosis of fetal hippocampal neurons induced by intrauterine distress-reoxygenation in rats. METHODS: Intrauterine ischemia was induced by clamping the uterine and uterine branch of the ovarian blood vessels with aneurysm clamps for a period of 15 min followed by removal of the clamps to permit reperfusion. Sprague-Dawley (SD) rats (n=12) were randomly divided into 4 groups on the 19th pregnant day: sham (S) group, LIP group, fetal distress (FD) group and LIP+FD group. The cesarean birth occurred on embryonic day 21 to obtain 12 fetal rats alive in each group. The fetal rats were decapitated and the pyramidal cells in CA1 hippocampus were observed under light microscope. The neuronal apoptosis was detected by terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling (TUNEL) staining and the apoptotic rate was calculated. The expression of Bcl-2 and Bax were detected by immunohistochemical method and Western blotting. RESULTS: The rates of neuronal apoptosis in FD group and LIP+FD group were significantly higher than that in S group (P<0.05), while no significant difference was observed between S group and LIP group (P>0.05). The expression of Bcl-2 and Bax in FD group and LIP+FD group was significantly higher than that in S group (P<0.05), while no significant difference was observed between S group and LIP group (P>0.05). The ratio of Bcl-2/Bax was lower in FD group than that in S group. Compared with FD group, the rate of neuronal apoptosis was significantly lower (P<0.05), while the ratio of Bcl-2/Bax was significantly higher (P<0.05) in LIP+FD group. CONCLUSION: Maternal limb ischemic preconditioning attenuates the apoptosis of fetal hippocampal neurons induced by intrauterine distress-reoxygenation in rats, which may be associated with the up-regulation of Bcl-2 expression.     

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.     

Mechanisms underlying the protective effect of renal ischemic preconditioning on ischemia-reperfusion myocardium of rabbits

AIM: To investigate the mechanisms underlying the protective effect of kidney ischemic preconditioning on rabbit myocardium in case of ischemia-reperfusion and the possible role of oxygen free radicals in the process. METHODS: Animals were divided into four groups: ischemia/reperfusion(I/R), classical ischemic preconditioning(CIPC), kidney ischemic preconditioning (KIPC) and superoxide dismutase in combination with kidney ischemic preconditioning(SOD+KIPC). The endo genous myocardial pretective material, nitric oxide(NO) and 5'-nucleotidase(5'-NT) were checked in four groups. RESULTS: As compared with I/R group, both CIPC and KIPC could ameliorate left ventricular function, reduce plasma PLA₂ activity and arrhythogenic rate also, the myocardial 5'-NT and NO production were significantly higher than that of the rabbit of I/R group. However, the protective effect on rabbit myocardium was significantly weakened by the SOD administration before the ischemic preconditioning. CONCLUSION: Protective effect of KIPC on myocardium may be due to increase in endo genous myocardial protective materials, oxygen free radicals may play an important role in the endo genous myocardial protective material release.     

Riboflavin preconditioning alleviates hepatic ischemia/reperfusion injury in rats

AIM: To explore the protective effect of riboflavin preconditioning on hepatic ischemia/reperfusion injury in rats. METHODS: Twenty-four Sprague-Dawley rats wererandomly divided into 3 groups (n=8): sham group, ischemia/reperfusion (I/R) group and riboflavin preconditioning (R+I/R) group. The rats in sham group and I/R group received a standard chow,while the rats in R+I/R group received a chow supplemented with riboflavin. After 4 weeks, portal vein and hepatic artery supplying the middle and left hepatic lobes were clamped with a traumatic vascular clip for induction of partial hepatic ischemia in the rats in I/R group and R+I/R group. After 1 h of ischemia, 1 h of reperfusion was conducted by removal of the clip. The activity of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) in serum,the activity of superoxide dismutase (SOD) and the level of malondialdehyde (MDA) in serum and liver were measured. Western blotting was employed to examine the protein expression of heme oxygenase-1(HO-1) in the liver. RESULTS: The results showed that ischemia/reperfusion injury markedly increased the activity of AST and ALT in serum, decreased the activity of SOD, and elevated the level of MDA and the activity of HO-1 in the liver as compared with sham group (P<0.01). The riboflavin pretreatment significantly decreased the activity of AST and ALT in serum, increased the activity of SOD and decreased the levels of MDA in serum and liver as compared with I/R group (P<0.01). In addition, the protein expression of HO-1 and the activity of HO-1 were elevated in R+I/R group (P<0.01). Cytoplasmic vacuolation and swelling of the hepatocytes were observed in I/R group. Treatment with riboflavin markedly alleviated the changes of liver structure. CONCLUSION: Riboflavin preconditioning has protective effect on hepatic ischemia/reperfusion injury. The mechanism may be correlated with enhancing the anti-oxidation and alleviating the reaction of lipid peroxidation.     

Role of renal cortex endothelin and NO in the development of proteinuria

AIM: To test the hypothesis that locally produced renal endothelin(ET) and nitric oxide(NO) play more important role in initiating proteinuria than circulating ET and NO. METHODS: (1) Rat nephrotic syndrome model was made by single injection of adriamycin, and the urinary protein excretion per 24 hours for every two days was measured. (2) Rat plasma and renal cortex were collected respectively 4 days, 8 days, 32 days and 56 days after the injection, and renal cortex homogenate was further prepared; ET of both plasma and renal cortex homogenate were determined by radioimmunoassay; NO of both plasma and renal homogenate were measured by the method of Griess. (3) The correlation between urinary protein and ET or NO concentration was analyzed respectively. RESULTS: (1) The urinary protein excretion of normal rat was 4-7 mg/d, that in nephrotic rat at the 4 time points was 5, 10, 241 and 201 mg/d, there was a significant increase of that at day 8, peaked at day 32, and less decrease at day 56. (2) The plasma ET in nephrotic rats of the 4 time points was 134, 150, 538 and 445 μg/L, respectively, which of day 8, day 32 and day 56 shown significant higher than that of normal control (126-129 μg/L). (3) The ET in renal cortex homogenate of nephrotic rat of the 4 time points was 364.6, 652.3, 1 526.8, 1 393.6 pg/g, all of that was much more higher than that of normal rat . (4) The plasma NO in nephrotic rat of the 4 time points was 40, 36, 8 and 11(μmol/L), there was considerable difference through day 8 to day 56 than control (42-46μmol/L, P＜0.05). (5) The NO in renal cortex homogenate of nephrotic rat was 80, 69, 8, 25 μmol/L that of normal rat was (114-124) μmol/L, there was significant difference between nephrotic rat and control from day 4 through day 56( P＜0.05). (6) The correlation coefficient of plasma ET and NO with separately urinary protein excretion shown statistic significance on only day 8 and day 56, while all of that of ET and NO in renal homogenate closely related with urinary protein from day 4 through to day 56. CONCLUSION: The ET and NO produced locally in renal play more important role in the development of proteinuria.     

Effect of ischemia/reperfusion on expression of endothelin in the rat ventral prostate and preventive measure

AIM:Effect of ischemia/reperfusion on expression of endothelin-1(ET-1) in the rat prostate and preventive measure were studied. METHODS:The abdominal aorta of rat was clipped briefly and repeatedly so as to treat the prostate with ischemia/reperfusion and expression of ET-1 mRNA in the ventral prostate was determined by RT-PCR.RESULTS:Expression of ET-1 mRNA in the ventral prostate was significantly increased at 1 h and 3 h after 90 min repeated ischemia/reperfusion (P＜0.05), and was not significantly changed after previous treatment of Dizocilpine maleate (MK-801) (P＞0.05). CONCLUSIONS:Expression of ET-1 in the prostate can be affected by repeated brief ischemia/reperfusion and it may play a role in the development of benign prostatic hyperplasia. Ischemia-reperfusion-induced ET-1 expression in the prostate of rats can be inhibited by prectreatment of MK-801.     

Effects of Ang Ⅱ on the production of ET-1, NO from adult rat myocardial fibroblasts

AIM: To investigate the effects of Ang Ⅱon the production of ET-1, NO from myocardial fibroblasts (MFs) of adult rat. METHODS: MFs were extracted by enzymatic digestion and anchorage velocity-dependent separation method. In this study, the changes of ET-1 and NO production from MFs in the second passage were examined by radioimmunoassay and by nitrate reductase-dependent assay, separatively. RESULTS: In a specific concentration range, AngⅡ increased ET-1 synthesis in MFs in a concentration-dependent manner. Losartan, the antagonist of angiotensin Ⅱ 1 type recepters (AT₁R), blocked the above effects. Ang Ⅱ may inhibit NO synthesis in MFs. When MFs were treated with losartan+Ang Ⅱ, the production of NO increased significantly, and was higher than that treated with the others (P<0.01). CONCLUSION: Ang Ⅱ may increase the production of ET-1 in MFs via AT₁R and affect NO production in MFs mainly via AT₁R to change the ratio of ET-1 and NO. Ang Ⅱ maybe exert inductive effects on myocardial hypertrophy and heart failure by affecting these complicated balances between bioactive factors produced from MFs.     

Protective effect of rapid ischemic preconditioning against spinal cord ischemic injury in rabbits

AIM: To evaluate the protective effect of rapid phase of ischemic preconditioning against spinal cord ischemic injury in rabbits. METHODS: Thirty six male New Zealands white rabbits were randomly assigned to 3 groups (12 in each group): ischemia and reperfusion injury group (IR group), ischemic preconditioning + IR group (IPC+IR group) and sham operation group (sham). In IR group, spinal cord ischemia was induced by an infrarenal aorta clamping for 20 min; The rabbits in IPC+IR group underwent a 6 min ischemic preconditioning followed by 30 min of reperfusion before the 20 min clamping; The rabbits in sham group underwent the same procedures as the IR group except for infrarental aortic unclamping. Neurologic status was scored at 8, 12, 24 and 48 h after reperfusion. All animals were sacrificed at 48 h after reperfusion and the spinal cords (L_5-7) were removed for histopathologic study and determination of the activity of Na⁺, K⁺-ATPase. RESULTS: The neurologic function scores in sham group and IPC+IR group at each observation interval were higher than those in IR group (P＜0.01). Compared to IR group, there were more normal neurons in anterior horn of spinal cord in sham group and IPC+IR group (P＜0.01); the activity of Na⁺, K⁺-ATPase in sham group and IPC+IR group were higher than those in IR group (P＜0.01). CONCLUSION: The rapid phase of ischemic preconditioning has a protective effect against spinal cord ischemic injury in rabbits, and this neuroprotection may be related to the maintenance of Na⁺, K⁺-ATPase activity.     

Apoptosis in rat hepatocytes with ischemia/reperfusion injury

AIM: To investigate the distributive rules of apoptosis index (AI) in liver with ischemia/reperfusion (I/R) injury and evaluate the factors related to the hepatocyte apoptosis. METHODS: Sixty SD rats in specific pathogen free grade were randomly divided into three groups: control group (n=18), sham operation group (n=18) and I/R group (n=24). In I/R group, liver injury was induced by blocking blood inflow in rat liver for 20 min, then reperfusion for 22 h. Rats in the control group didnt receive any management. Rats in the sham operation group only subjected sham operation. All rat blood samples and livers were obtained for determination. Blood serum ALT, AST, TBIL, TNF-α, IFN-γ, IL-4, plasma endotoxin concentration, MDA level and SOD activity in liver were detected. Hepatic histological analysis was conduced through HE staining. Apoptosis was detected by TUNEL methods. RESULTS: Focal necrosis occurred in six rats livers in I/R group, in control group and sham group no necrosis cell was found in livers. The hepatic AI of I/R group was significantly increased compared with other groups. The AI in region under hepatic amicula was higher than that in central veins region and portal area. The necrotic regions contained apoptotic cells and AI was higher than that of other regions. Hepatic AI was significantly associated with ALT, AST, TNF-α, IFN-γ and SOD/MDA. CONCLUSION: In liver with I/R injury, the apoptotic cells in the region under hepatic amicula and the focus of necrosis are significantly higher than those in other regions, apoptotic cells and necrosis cells co-exist in the same zone. Hepatic AI may be significantly associated with ALT, AST, TNF-α and SOD/MDA.     

Remote preconditioning provides myocardial protection against myocardial ischemia/reperfusion injury through downregulating the expression of calreticulin in rats

AIM: To evaluate the role of calreticulin (CRT) in myocardial protection of remote preconditioning against myocardial ischemia/reperfusion injury. METHODS: Thirty SD rats were randomly divided into 5 groups: ischemia reperfusion group (IR), ischemia preconditioning group (IP), remote preconditioning group Ⅰ (RPI), remote preconditioning group Ⅱ (RPII) and pseudo-operation group (PO). The ischemia/reperfusion model was established in vivo. Hemodynamic changes of heart function were observed. Serum cardiac troponin T (cTnT), superoxide dismutase (SOD), malondialdehyde (MDA) and the expression of calreticulin in myocardium were detected. RESULTS: Hemodynamic data, serum cTnT, DA, SOD and the expression of CRT in RPI and IR group were not statistically different (P>0.05). SOD level in IP and RPII group was higher than that in IR group (P<0.05). Accordingly, cTnT, MDA and the expression of CRT in these two groups were lower than those in IR group (P<0.05). CONCLUSION: Remote preconditioning may mimic the protective effect of ischemic preconditioning. Remote preconditioning attenuates myocardial ischemia/reperfusion injury in vivo possibly through down-regulation of CRT expression in rats.     

Role of heme oxygenase-1 in the ischemic preconditioning of isolated rat heart

AIM: To investigate the influence of ischemic preconditioning on heart function, the activities of lactate dehydrogenase (LDH), malondialdehyde (MDA), and heme oxygenase-1 (HO-1) after ischemia/reperfusion in isolated rat heart. METHODS: The model of Langendorff was used in isolated rat heart perfusion. Ischemic preconditioning protocol: stopping perfusion for 5 minutes and reperfusion for 5 minutes, repeating three times. Ischemia protocol: stopping perfusion for 40 minutes and reperfusion for 20 minutes. Indexes of heart function were recorded in control M8, ischemia and reperfusion group (IR), and ischemic preconditioning group (IPC). The content of LDH of coronary effluent was measured. Moreover, the content of MDA and activity of HO-1 in myocardium were also measured. RESULTS: The recovery percentage of heart function in IPC group was significantly higher than that in IR group (P<0.01) and the activity of heme oxygenase-1 also increased significantly (P<0.05). CONCLUSION: The contents of LDH and MDA significantly decreased in IPC group compared with IR group. The increase in heme oxygenase-1 activity might be involved in the protective effect of ischemic preconditioning on ischemic/reperfused rat heart.