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Mechanisms Of Tau And GR Reduced The Myocardial Ischemia-Reperfusion Induced Oxidative Injury

Posted on:2013-03-02Degree:MasterType:Thesis
Country:ChinaCandidate:S ZhangFull Text:PDF
GTID:2234330374998560Subject:Pharmacology
Abstract/Summary:PDF Full Text Request
Objective:To study protective effects of the taurine (Tau) and gradual reperfusion (GR) reduced I/R-induced rats oxidative damage in vitro, and to explore whether through the Akt and the Erk signal pathway.Methods:Isolated myocardial ischemia-reperfusion (I/R) model was replicated by Langendorff perfused rat heart. Sprague-Dawley rats were randomLy divided into seven groups:normal (Nor) group, I/R group, GR group, taurine of lower concentration (T20) group, Tau of higher concentration (T40) group, GR combined with Tau of lower concentration (GT20) group and GR combined with Tau of higher concentration (GT40) group. The cardiac function was recorded, including the left ventricular developing pressure (LVDP),+dp/dtmax,-dp/dtmax and coronary flow (CF). The LDH activity of each group and the myocardial infarct size were observed. Changes of myocardial morphology were observed after HE staining. The activity of the total superoxide dismutase (total superoxide dismutase, T-SOD) and Mn superoxide dismutase (superoxide dismutase of Mn, Mn-SOD) and the content of malondialdehyde (MDA) were measured. In the next step the Akt and Erk protein phosphorylation levels of myocardial tissue were detected by Western blot.Results:1. The myocardial ischemia-reperfusion induced oxidative injury was reduced by Tau and GR.Compared with I/R group, the LVDP,+dp/dt max,-dp/dtmax were significantly improved, the CF was significantly decreased after90min reperfusion, LDH and myocardial infarct size were decreased significantly in GR, GT20, and GT40groups. Compared with the I/R group, the T-SOD (124.26±12.49,140.76±10.36,163.13±16.30vs.100.68±7.86, P<0.01) and Mn-SOD (74.86±7.03,81.65±7.02,96.31±7.03vs.48.06±5.11,P<0.01)content were significantly improved and MDA (1.98±0.16,1.86±0.11,1.37±0.15vs.2.28±0.18, P<0.05, P<0.01)content was decreased in GR, GT20and GT40groups.2. The Akt pathway may be activated in the myocardial protective effects of GR and Tau reduced I/R-induced oxidative injury in vitro.Western blot showed that p-Akt protein expression levels in myocardial tissue (P<0.01) was significantly increased in the GR, GT20, GT40group, but p-Erk protein expression level was not statistically different.Conclusion:1. The myocardial coronary flow was increased and the myocardial infarct size was reduced by GR and Tau. The recovery of myocardial function was promoted. Oxidative stress damage was reduced by GR and Tau. Tau preconditioning joint GR has a better protective effect on myocardial ischemia. The intensity is stronger than a single gradual perfusion or Tau.2. The phosphorylation of Akt was promoted by GR and Tau. The Akt pathway may be activated in vitro that was the mechanisms of GR and Tau reduce I/R-induced myocardial oxidative damage.
Keywords/Search Tags:taurine, gradual perfusion, cardiac function, oxidative stress, SOD, MDA, Akt signaling pathway
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