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The Protective Effect Of α-lipoic Acid On Myocardial Injury In Diabetic Rats

Posted on:2013-07-29Degree:MasterType:Thesis
Country:ChinaCandidate:Y P KangFull Text:PDF
GTID:2234330395966170Subject:Pharmacology
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ObjectiveExplore α-lipoic acid diabetic rats myocardial injury to the protection andpossible mechanism, for its further development of diabetes drug andmyocardial injury treatment provides the basis.MethodsThe fifty Sprague-Dawley (SD) rats were randomly selected forty rats afterfasting for12hours. The diabetic model was established followingintraperitoneal injection of streptozocin with45mg/kg. The remaining ten ratswere injected intraperitoneally with citrate buffer solution of the same dose asthe normal control group. The DM rats were randomly divided into four groups:the diabetic model group, α-lipoic acid of15,30,60mg/kg·d was given to thedrug therapy group. After12weeks, rats were respectively measured fastingblood glucose, heart function and serum fructosamine. Myocardium wasobserved collagen fiber and pathologic changes with HE staining.Semiquantitative expressions of MMP-2, MMP-9and TIMP-1protein weredetermined by immunohistochemistry and Western Blot.ResultsCompared with the normal control group, fasting blood glucose of thediabetic rats was significantly up-regulated (P<0.01);+dp/dtmaxand-dp/dtmaxwere declined significantly (P<0.01) by heart function measured; serumfructosamine of the diabetic rats was increased remarkably (P<0.01); Myocardial tissue damaged obviously, broken in muscle fiber, intercellularwidened and collagen volume fraction increased significantly (P<0.01); Theprotein expression of MMP-2, MMP-9, TIMP-1and MMP-9/TIMP-1weresignificantly up-regulated (P<0.01). Compared with the diabetic model group,three doses of α-lipoic acid relieved these damages. Fasting blood glucose ofα-lipoic acid therapy groups was significantly decreased (P<0.01);+dp/dtmaxand-dp/dtmaxwere elevated (P<0.05or P<0.01) by heart function measured; serumfructosamine of α-lipoic acid therapy groups was significantly decreased(P<0.01); the pathological myocardial structural damage and diabetic modelgroup compared to the significant improvement in myocardial tissue returned tonormal(P<0.01);MMP-2, MMP-9, TIMP-1and MMP-9/TIMP-1were significantlydecreased (P<0.01).Conclusion1. A-lipoic acid can significantly reduce blood sugar and serumfructosamine level.2. The protective effect of α-lipoic acid may relate to improve heartfunction, reduce cell damage, inhibit collagen hyperplasia and improvemyocardial pathological structure.3. A-lipoic acid can decrease the high expression of MMP-2, MMP-9andTIMP-1, reduce MMP-9/TIMP-1ratio, and then attenuate theremodulation of myocardium.
Keywords/Search Tags:A-lipoic acid, Diabetic cardiomyopathy, Matrix metalloproteinases-2, Matrixmetalloproteinases-9, Tissue inhibitors of matrix metalloproteinase-1
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