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The Effect of Dantrolene Pretreatment on Myocardium Ischemia Reperfusion Injury

Author: CaoYing
Tutor: YuGongYuan
School: Tianjin Medical University
Course: Biochemistry and Molecular Biology
Keywords: Ischemia-reperfusion Dantrolene Pretreatment Hemodynamic Mitochondrial swelling ATP enzyme Ryanodine receptor Calcium release
CLC: R965
Type: Master's thesis
Year: 2011
Downloads: 16
Quote: 0
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Abstract


Objective To investigate the dantrolene pretreatment on isolated rat hearts ischemia-reperfusion injury. Concept Chadan sertraline pretreatment on isolated rat cardiac blood flow dynamics, lactate dehydrogenase activity, infarct size, mitochondrial Na, K-ATPase and Ca-ATP enzyme activity, the degree of swelling of mitochondria, muscle sarcoplasmic reticulum ryanodine speed and amount of alkali receptor calcium release and sarcoplasmic reticulum Ca2-ATP activity. Methods 48 Wistar rats were randomly divided into three groups, the control group, ischemia-reperfusion group and dantrolene group, n = 16. Establish Langendorff isolated heart perfusion model. Control group heart perfused with Krebs solution 120min; ischemia-reperfusion group with Krebs solution perfusion, the heart to maintain sustained for 30 min after ischemia for 30 min, reperfusion 60 min; the dantrolene group in perfusion balance 5 minutes, 10 minutes and 20 minutes, Jia Rudan sertraline, so that the circulation system in the final concentration of dantrolene 1μmol / l, 3 μmol / l, 5μmol / l so that the heart in the state of joining the drug to maintain a working 25min, and then ischemia 30 min, reperfusion 60 min. Each group randomly selected eight measurements of heart rate (HR), aortic flow (AF), coronary flow (CF), cardiac output (CO), the perfusate of lactate dehydrogenase (LDH) activity as well as the myocardial infarct size, and the other 8 differential centrifugation extraction of mitochondria, the measurement of the Na, K-ATPase and Ca2 - ATPase activity of mitochondrial swelling degree. Supernatant by ultracentrifugation method to extract the sarcoplasmic reticulum the measured calcium ATP enzyme (SERCA) activity, calcium intake, and the ryanodine receptor (RyR) calcium release. Results 1.5min when stabilization period, the difference between the three groups the indicators were not statistically significant. 10min, 20min, three groups of indicators no significant difference. Dantrolene group coronary flow and control group in 30min and ischemic reperfusion group compared to a slight increase (P lt; 0.05). The rest showed no significant difference. Control group without infarction, and lower LDH activity in the perfusate. Dantrolene group compared with ischemia-reperfusion group, infarct size was reduced by approximately 24.1%, the dantrolene group LDH activity than the control group decreased by 32.2%; were higher compared with the control group, the infarct size and LDH activity (P lt; 0.05). 3. Ischemia-reperfusion group mitochondrial Na, K-ATPase enzyme activity, Ca2-ATP enzyme activity compared with the the dantrolene group and control group were lower (P lt; 0.05), but the the dantrolene group and the control group had no statistics learning differences. Ischemia-reperfusion group and dantrolene group, the degree of swelling of mitochondria compared with the control group, but the dantrolene group compared with ischemia-reperfusion group (P lt; 0.05). . The dantrolene group sarcoplasmic reticulum RyR calcium release early speed and the maximum ratio of the control group and ischemia reperfusion group were low, and ischemia reperfusion group compared with the control group (P lt; 0.05). 6 the dantrolene group of SERCA activity, calcium intake maximum speed and maximum amount ischemia-reperfusion group showed no significant differences, but both are lower than the control group (P lt; 0.05). Conclusion 1. Dantrolene pretreatment to change hemodynamic weak. Dantrolene concentration 5μmol / l, an increase in coronary blood flow can improve myocardial blood supply and thus, to some extent, to relieve myocardial ischemia. Dantrolene pretreatment can be reduced myocardial infarct size; reduce ischemia-reperfusion injury in myocardial cells LDH release, has a protective effect on ischemia-reperfusion injury myocardium. Dantrolene pretreatment can protect the mitochondrial Na, K-ATPase and Ca2-ATP enzyme activity, reduce the degree of swelling of mitochondria, decreased myocardial ischemia-reperfusion injury. Dantrolene pretreatment may inhibit cardiac myocyte sarcoplasmic reticulum RyR calcium release, thereby reducing myocardial ischemia-reperfusion injury.

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