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Study On The Protection Of Noninvasive Delayed Limb Ischemic Preconditioning Against Myocardial Ischemia-reperfusion-induced Oxidative Injury In Rats With Four-week Duration Of Diabetes Mellitus

Posted on:2014-11-02Degree:MasterType:Thesis
Country:ChinaCandidate:L WangFull Text:PDF
GTID:2254330401961020Subject:Pharmacology
Abstract/Summary:PDF Full Text Request
Objective:To study the protection of noninvasive delayed limb ischemic preconditioning(NDLIP) against myocardial ischemia/reperfusion oxidative injury in diabetic rats (four-week duration).Methods:Diabetic rat models(four-week duration) were induced by injection of streptozotocin(STZ) into the vena caudalis. The diabetic rats were divided randomly into four groups.(1) Sham group:rats were threaded a silk suture under the left coronary artery anterior descending(LAD) and laid up throughout the experiment.(2) myocardial ischemia/reperfusion (I/R) goup:rats were subjected to30min occlusion and120min reperfusion of LAD;(3) early myocardial ischemic preconditioning (EMIP)goup:rats were subjected to three episodes of5min of ischemia coupled to5min of reperfusion in the LAD before30min occlusion and120min reperfusion of LAD;(4) NDLIP goup:rats were pretreated with three cycles of5min ischemia/5min reperfusion on the left hind limb, once a day for three consecutive days, to establish the NDLIP models. On the forth day,30min occlusion and120min reperfusion of LAD was performed. The electrocardiogram was monitored continuously to record ventricular arrhythmia (VA) during30min ischemia. I/R-induced infarct size was determined using2,3,5-triphenyltetrazolium chloride (TTC) staining. Activities of myocardial tissue myeloperoxidase (MPO), total superoxide dismutase (T-SOD) manganese superoxide dismutase (Mn-SOD), glutathione peroxidase (GSH-PX) and xanthine oxidase (XOD), content of myocardial malonaldehyde (MDA) in serum were detected by spectrophotometer.Results:1. Effects of NDLIP on changes of cardiac physiological function induced by myocardial I/R injury.Compared with I/R group, the extent of ST-segment was degraded (P<0.01) in EMIP group and NDLIP goup; onsets of ventricular premature contraction (VPC) and ventricular tachycardia (VT) were delayed (VPC:16.85±1.81vs6.32±1.29, P<0.01; VT:21.71±2.23vs8.76±2.13,P<0.01), durations of them were shortened (VPC:5.28±2.54vs15.09±5.23, P<0.01; VT:3.54±1.11vs5.74±2.56, P<0.05) in EMIP group; durations of VPC were shortened (9.60±1.98vs15.09±5.23, P<0.05) in NDLIP group. Changes of MAP and HR caused by I/R injury were not influenced by EMIP and NDLIP.2. Effects of NDLIP on myocardial cell injury and necrosis induced by myocardial I/R injury.Compared with I/R group, the myocardial infarct size was diminished (IS/AAR%:18.88±6.96and27.47±4.86vs48.06±6.26, P<0.01), activity of MPO was attenuated (1.70±0.41and1.62±0.42vs2.76±0.48, P<0.01), and the injury of myocardial morphous was improved in EMIP group and NDLIP group. However, the NDLIP group had significant differences in diminishing myocardial infarct size against I/R injury when when compared with EMIP group (IS/AAR%:27.47±4.86vs18.88±6.96, P<0.05). The protection of NDLIP was less than that of EMIP.3. Effects of NDLIP on myocardial antioxidative activity after myocardial I/R injuryCompared with I/R group, activity of XOD (30.09±1.85and28.47±1.24vs36.35±2.16, P<0.01) and content of MDA (1.31±0.23and1.39±0.24vs3.24±0.24, P<0.01) were decreaed in EMIP group and NDLIP group; activities of T-SOD(232.49±17.53vs206.10±7.07, P<0.01), Mn-SOD(112.09±6.43vs88.98±7.32, P<0.01) and GSH-PX(87.39±8.62vs68.58±5.84, P<0.01) were increased in EMIP group. The activities of T-SOD, Mn-SOD and GSH-PX in NDLIP group, had no significant differences when compared with I/R group. The protection of NDLIP was less than that of EMIP.Conclusion:1. NDLIP decreased the extent of ST-segment increase induced by I/R injury, shortened durations of VPC. The effect of NDLIP on anti-ventricular arrhythmias was less than that of EMIP in diabetic myocardium. Changes of MAP and HR caused by I/R injury were not influenced by NDLIP.2. NDLIP diminished myocardial infarct size and improved myocardial morphology after I/R injury. The protective effect of NDLIP against cell injury and necrosis was less than that of EMIP in diabetic myocardium. The decline in activity of MPO may contribute to the protection. 3. NDLIP alleviated myocardial oxidative stress after I/R injury to decrease peroxidative injury, that was less than the extent of EMIP in diabetic myocard.
Keywords/Search Tags:noninvasive delayed limb ischemic preconditioning, diabetes mellitus, delayed cardioprotection, myocardial infarction, the ability of apoptosis antioxiditive injury
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