Font Size: a A A

The Influence And Function Mechanism Of Recombinant Human Brain Natriuretic Peptide (RhBNP) On Experimental Myocardial Ischemia-reperfusion Injury In Rats

Posted on:2011-12-12Degree:MasterType:Thesis
Country:ChinaCandidate:L WangFull Text:PDF
GTID:2144360305954810Subject:Internal Medicine
Abstract/Summary:PDF Full Text Request
Coronary atherosclerotic heart disease increasingly threatening human life, By 2020, coronary heart disease will become one of the main causes of death in the world, While AMI is the leading cause of death. For patients with AMI, rapid recovery flow is the most effective method to save ischemic myocardium. But the experimental and clinical study showed that reperfusion injury can swap quickly recovery flow sometimes. In 1977, Hearse proposed the concept of ischemia-reperfusion injury firstly. So-called IRI refers to cells happen reversible and survival injury because of ischemia. After ischemia corrected, the more serious injury cause cell death or further dysfunction. Myocardial is one of the most common tissue of the IRI, the mechanism may be related with many factors.RhBNP is mainly used in the treatment of acute heart failure. Although experiments have shown rhBNP can dilating coronary artery and improving coronary blood flow, increase myocardial blood and oxygen supply, improve cardiac function.But the drug for myocardial ischemia-reperfusion injury in the study was rarely reported, this observation of recombinant human brain natriuretic peptide on myocardial ischemia-reperfusion injury in rats and its mechanism, was for the right treatment of myocardial ischemia-reperfusion injury in new ways to provide experimental basis.Methods:The myocardial ischemia-reperfusion model was induced by 30 min left anterior descending coronary occlusion and 4h reperfusion in rats, sublingual administration of drugs. Each group to take 10, measured serum CK, LDH, AST activity, each group to take the other 10, measured serum MDA, SOD, MPO.10 rats in each group, cut to take heart, NBT staining, calculation MIS. To take five rats in each group, made specimens from the heart, ice-saline washed, in part at 4%paraformaldehyde fixed, ordinary light microscope detection; another part was fixed in 2.5%glutaraldehyde, transmission electron microscopy examination. To take five rats in each group, specimens from the heart, placed with 1%diethyl pyrocarbonate 4%paraformaldehyde fixative fixed 24h, conventional dehydration, embedding, slicing, in order to immunohistochemical detection of myocardial cell caspase-3 expression, and cardiomyocyte apoptosis detected with TUNEL.Results:(1) compared with sham-operated group, myocardial ischemia-reperfusion injury model group, the MIS and AST, LDH, CK activity were significantly increased (P<0.05-P<0.001), SOD activity was significantly decreased, MDA, and MPO levels were significantly increased (P<0.05); And myocardial ischemia-reperfusion injury model group, recombinant human brain natriuretic peptide (rhBNP) group, the MIS and AST, LDH, CK activity was significantly decreased, SOD activity was significantly increased, MDA, and MPO levels were significantly reduced. (2) Light microscopy:sham operation group structured myocardial fibers, myocardial cells, no necrosis, myocardial interstitial edema-free. MIR group of myocardial fibers disorder, myocardial cells, seen necrosis, myocardial interstitial edema. rhBNP Group:myocardial fibers slightly thicker, more structured arrangement, a small amount of necrotic myocardial cells can be seen, no significant myocardial interstitial edema. ((3) The electron microscope results:sham-operated group tow rows of muscle, the sarcomere with a visible light and shade, no abnormal mitochondria. MRI Group: muscle tow a partial rupture and dissolution of local availability of mitochondrial changes. RhBNP:muscle Tow still neatly arranged, the sarcomere is still light and shade with a clear, localized changes in mitochondria to reduce cavitation. (4) Immunohistochemical Results:Compared with sham-operated group, myocardial ischemia-reperfusion injury model group, the caspase-3 expression and apoptosis index were significantly higher; and myocardial ischemia-reperfusion injury model group, recombinant human brain natriuretic peptide (rhBNP) group of caspase-3 expression and apoptosis index were significantly decreased.To sum up:Recombinant human brain natriuretic peptide (rhBNP) on experimental myocardial ischemia-reperfusion injury in a clear protective effect may be related to enhanced activities of antioxidant enzymes to reduce free radicals on myocardial oxidative injury and to reduce microvascular damage, anti-apoptosis.Conclusion:RhBNP effectively reduces acute myocardial infarct size and myocardial three enzymes of ischemia-reperfusion in rats, and from the pathological changes, it is proved to have a protective effect for myocardial ischemia-reperfusion. A protective effect mechanism of rhBNP for myocardial ischemia-reperfusion is multi-target, and may reduce the myocardial membrane lipid peroxidation and enhance antioxidant capacity of myocardial cells and reduce cell apoptosis and other mechanisms.The results of the research for myocardial ischemia and reperfusion injury prevention and treatment method provides a new experimental basis, and has important theoretical significance and broad application prospect.
Keywords/Search Tags:recombinant human brain natriuretic peptide (rhBNP), ischemia-reperfusion, myocardial enzymes, free radicals, caspase-3
PDF Full Text Request
Related items