ABSTRACT
AIM: To explore whether free radicals participate in cerebral ischemic tolerance and the up-regula-tion of p38 MAPK and ERK signaling pathways in rats induced by limb ischemic preconditioning (LIP). METHODS: A total of 128 Wistar rats with permanent occlusion of bilateral vertebral arteries were randomly divided into sham group (n=16), cerebral ischemia (CI) group (n=16), LIP+CI group (n=16), DMTU (a free radical scavenger)+LIP+CI group (n=64) and DMTU+sham group (n=16). Six rats in each group were used to observe the delayed neuronal death (DND) in hippocampal CA1 region by thionin staining at 7 d after the end of operation. Other 10 rats in each group were used to de-tect the expression of p38 MAPK and ERK in hippocampal CA1 region by immunohistochemistry and Western blot. RE-SULTS: Lethal CI resulted in obvious DND in hippocampal CA1 region. However, LIP reversed the above injurious changes, represented by the decrease in histological grade and the increase in neuronal density compared with CI group (P<0. 01). Moreover, LIP significantly up-regulated the expression of p38 MAPK and ERK in hippocampal CA1 region com-pared with CI group (P<0. 01). Administration of free radical scavenger DMTU via femoral vein before LIP partially re-versed the neuroprotective effect of LIP, and blocked the up-regulation of p38 MAPK and ERK expression in hippocampal CA1 region in rats compared with LIP+CI group (P<0. 01). CONCLUSION: Free radicals are involved in the neuropro-tection and up-regulation of p38 MAPK and ERK expression induced by LIP in rats.
ABSTRACT
AIM:To study the effects of noninvasive delayed limb ischemia preconditioning ( NDLIP) on ani-mal cardiac function , myocardial morphology and myocardial apoptosis after myocardial infarction ( MI ) .METHODS:Healthy SD male rats [n=45, weighing (250 ±10) g] were randomly divided into 3 groups:MI group:the animal model of MI was established by surgical ligation of left anterior descending artery ( LAD) after 2 weeks;NDLIP group:after the success of the MI animal model , NDLIP was carried out every other day until the 4th, 6th and 8th weeks;sham group:as the negative control group , the animals were taken heart LAD threading but no ligation .All rats were fed conventionally .At the end of the 4th, 6th and 8th weeks, all rats were made ventricular intubation , and then the hemodynamic parameters were recorded .The blood samples were withdrawn from the abdominal aorta and the serum was separated via centrifugation . The serum contents of Bcl-2 and Bax were measured by ELISA .Left ventricular anterior wall was homogenized .The mito-chondrial respiratory chain complexes Ⅰ,Ⅱ,Ⅲand Ⅳin the myocardial tissues were detected by ELISA .RESULTS:At the end of the 4th, 6th and 8th weeks, compared with MI group, left ventricular systolic pressure in NDLIP group was significantly increased , while left ventricular end-diastolic pressure in NDLIP group was significantly decreased ( both P<0.05).Mitochondrial respiratory chain complexesⅠ, Ⅱ, Ⅲ and Ⅳ in NDLIP group were significantly increased (P<0.05).The serum level of Bcl-2 in NDLIP group was significantly increased and Bax level was reduced remarkably (both P<0.01) .CONCLUSION:NDLIP improves the hemodynamic indexes , promotes the mitochondrial respiratory function and inhibits cell apoptosis , thus improving the prognosis of MI .
ABSTRACT
Aim To study the preventative effects of noninvasive delayed limb ischemic preconditioning ( NDLIP) on sudden cardiac death in rats with myocar-dial infarction. Methods Thirty healthy SD male rats weighting ( 250 ± 10 ) g were randomly divided into 3 groups:① myocardial infarction ( MI ) group: animal model of MI was established by making surgical ligation of animal LAD. ② MI plus NDLIP group: after the success of the animal model of MI, NDLIP was carried out every other day until 4th week. ③Sham group:as the negative control group, animals were taken heart LAD threading but no ligation. All rats were fed con-ventionally. At the end of 4 weeks, three groups of rats were administered with metaraminol ( 0. 2 mg · min-1 ) . ECG, drug cumulant of sudden death and death onset time were recorded. After sudden death, blood samples were withdrawn from abdominal aorta and serum was separated via centrifugation. ELISA method was used to measure serum caspase-3 , HSP70 and SOD concentration. Results While metaraminol led animal cardiac sudden death, the rats heart rate ( HR) kept declining with the increase of dosage of metaraminol during the administration period. Rat HR of MI+NDLIP group [ ( 479 ± 8 ) vs ( 416 ± 19 ) beat ·min-1 , ( 446 ± 32 ) vs ( 370 ± 20 ) beat · min-1 , (376 ± 53) vs (305 ± 29) beat·min-1, (307 ± 63) vs (244 ± 33) beat·min-1, (283 ± 45) vs (121 ± 35 ) beat · min-1 , P <0. 01 ] was markedly higher than that of MI group at 0 , 5 , 10 , 30 , 50 min before death. Compared with MI group, drugs cumulant to sudden death and death onset time of MI + NDLIP group [ ( 14. 58 ± 3. 03 ) vs ( 10. 76 ± 2. 73 ) mg, (72. 9 ± 15. 2 ) vs ( 53. 8 ± 13. 6 ) min, P <0. 01 ] were significantly increased. Compared with MI group, serum caspase-3 content of MI+NDLIP group was sig-nificantly reduced [ ( 2. 01 ± 0. 52 ) vs ( 2. 34 ± 0. 38 )μg·L-1 , P<0. 01 ]; HSP70 levels were remarkably increased [ ( 3. 01 ± 0. 58 ) vs ( 2. 70 ± 0. 43 ) μg · L-1 , P <0. 05 ]; SOD levels were significantly im-proved [(1. 99 ± 0. 65) vs (1. 70 ± 0. 58) mg·L-1, P<0. 01 ] . Conclusion NDLIP can prevent sudden cardiac death after myocardial infarction in rats, which may be mediated by reducing the myocardial cell apop-tosis, increasing protective protein expression and en-hancing antioxidant capacity.
ABSTRACT
AIM: To investigate the effects of the sera from the rats after limb ischemic preconditioning (LIPC) on human umbilical vein endothelial cells (HUVECs) injured by hydrogen peroxide (H2O2).METHODS:The HUVECs were divided into 5 groups:the cells in control group were cultured without any intervention;the cells in model group (M) were damaged by 1 mmol/L H2O2 for 2 h;the cells in early preconditioning serum (EPS) group, delayed pre-conditioning serum (DPS) group or sham limb ischemic preconditioning serum (SPS) group were treated with the corre-sponding serum at 5%for 12 h, respectively , and then treaed with H 2 O2 for 2 h.The viability of the HUVECs was ana-lyzed by flow cytometry .The lactate dehydrogenase ( LDH) in the culture media was detected .The cell adhesion molecules in the HUVECs were detected by real-time PCR.The mRNA and protein expression of heme oxygenase-1 (HO-1) was also determined .RESULTS:The viability of HUVECs incubated with 1 mmol/L H2 O2 for 2 h significantly decreased compared with the control cells , which was accompanied with the augmentations of LDH in the medium and the cell adhesion mole -cules in cells , such as vascular cell adhesion molecule-1 ( VCAM-1 ) and intercellular adhesion molecule-1 ( ICAM-1 ) . Preincubation with EPS and DPS derived from the rats subjected LIPC attenuated these injuries .Furthermore, pretreatment with EPS and DPS increased the expression of HO-1 at mRNA and protein levels .CONCLUSION:LIPC protects the HU-VECs from H2O2-induced injury.
ABSTRACT
@#Objective To observe the brain glucose metabolism after limb ischemic preconditioning (LIPC) for ischemic moyamoya disease with positron emission tomography (PET) and statistical parametric mapping (SPM). Methods 62 patients with ischemic moyamoya disease were enrolled and randomized into LIPC group (n=31) and control group (n=31). The glucose metabolism of patients was analyzed with PET before and after treatment in both groups, using the methods of radioactivity ratio and SPM. Results The glucose metabolism ratio improved more in the LIPC group than in the control group (P<0.01), and aggravated less than in the control group (P<0.001). As setting the glucose metabolism increased after treatment, there were 7 areas activated in LIPC group, including frontal, temporal and parietal lobes, and the KE=1121; while there were 5 areas activated in the control group, including frontal and parietal lobes, and the KE=292. As setting the glucose metabolism decreased after treatment, there was only frontal area activated in LIPC group, while there were 8 areas activated in the control group, including frontal, parietal, occipital lobes, and the KE=629. Conclusion LIPC may improve the brain glucose metabolism in patients with moyamoya disease, which can be observed with PET and SPM.
ABSTRACT
Objective To observe the brain glucose metabolism after limb ischemic preconditioning (LIPC) for ischemic moyamoya dis-ease with positron emission tomography (PET) and statistical parametric mapping (SPM). Methods 62 patients with ischemic moyamoya disease were enrolled and randomized into LIPC group (n=31) and control group (n=31). The glucose metabolism of patients was analyzed with PET before and after treatment in both groups, using the methods of radioactivity ratio and SPM. Results The glucose metabolism ratio improved more in the LIPC group than in the control group (P<0.01), and aggravated less than in the control group (P<0.001). As setting the glucose metabolism increased after treatment, there were 7 areas activated in LIPC group, including frontal, temporal and parietal lobes, and the KE=1121;while there were 5 areas activated in the control group, including frontal and parietal lobes, and the KE=292. As setting the glu-cose metabolism decreased after treatment, there was only frontal area activated in LIPC group, while there were 8 areas activated in the con-trol group, including frontal, parietal, occipital lobes, and the KE=629. Conclusion LIPC may improve the brain glucose metabolism in pa-tients with moyamoya disease, which can be observed with PET and SPM.
ABSTRACT
Aims To investigate the protective effects of noninvasive limb ischemic preconditioning (LIPC) on myocardial ischemia-reperfusion (I /R)injury,and to explore the mechanism.Methods Healthy male Wistar rats were divided randomly into I /R,I /R +LIPC,I /R +5-Hydroxydecanoate (5-HD)and I /R +LIPC +5-HD groups.The I /R +LIPC and I /R +LIPC-5-HD groups of rats were subjected to three cy-cles of LIPC induction per day with 5 min of reperfu-sion after occlusion for 5 min at the left hind limb for 3 days.All rats were subjected to myocardial I /R injury on the fourth day.The I /R +5-HD and I /R +LIPC-5-HD groups of rats were given the inhibitor of ATP-sen-sitive potassium channel 5-HD before and during myo-cardial I /R injury. Results Compared with I /R group,LIPC reduced myocardial infarct size (P <0.05),lowered cardiocyte apoptosis index and Fas, FasL positive cell number (P <0.01 ),increased the reduced nitric oxide (NO)/endothelin (ET)-1 ratio (P <0.05)in serum in I /R +LIPC group.5-HD a-bolished the protective effects induced by LIPC in I /R+LIPC-5-HD group.Compared with normal myocardi-al tissue,expression of mir-30a-3p was increased in I /R group (P <0.01 )and was decreased in LIPC group (P <0.01 ).Conclusion LIPC alleviates myocardial I /R injury and improves endothelial function. The mechanism may be related with the opening of ATP-sensitive potassium channel,regulating the balance be-tween NO and ET-1 and decreasing the expression of myocardial mir-30a-3p.