| [Objective]The precise mechanism of pharmacological postconditioning alleviating myocardial ischemia-reperfusion injury(MIRI) remain undefined, and whether patients with type 2 diabetes mellitus(T2MD) can still benefit from it is still debated. Toll-like receptor 4(TLR4), as one kind of pattern recognition receptors, is becoming increasingly valued in this field due to its role in mediating inflammatory reaction, which might be crucial ties of myocardial ischemia-reperfusion injury and type 2 diabetes mellitus. The research is to observe whether the protection of atorvastatin post-treatment against MIRI in rats with T2 DM is related to TLR4 signaling pathway. [Methods]Forty five steady diabetic rat models induced by intraperitoneal injection of streptozotocin(STZ) after four weeks’ diet of high-sucrose and high-fat were randomly divided into five groups(sham, IR, AP, LPS and LPS+AP group, nine in each group) to produce the models of MIRI. All groups except sham-operated group were subjected to ischemia for 30 minites by ligation of left anterior descending coronary artery(LAD) and suffered reperfusion for 120 minites subsequently, during which period each group was underwent different treantment respectively. Areas of myocardial ischemia and infarction were determined by evans blue and triphenyltetrazolium chloride(TTC) staining. The activation and expression levels of TLR4 and myeloid differentiation factor 88(My D88) m RNA and protein in ischemic myocardium were detected by RT-PCR and Western Blot respectively. [Results]Obvious area of ischemia or infarction was not found in sham group. Compared with IR group, the AP group significantly decreased the myocardial infarct size, while the LPS group markedly increased. And the LPS+AP group showed a notable smaller infarction than LPS group.(all P<0.05)Additionally, TLR4, My D88 m RNA and protein were expressed remarkably higher in each other group than in sham group. Furthermore, compared to IR group, the AP group reduced the expression evidently, while the LPS group raised dramatically. However, when added atorvastatin post-treatment, the LPS+AP group showed a significant lower level of these expression.(all P<0.05) [Conclusion]Thus, we draw conclusion from these data that the activation of TLR4 and My D88 promoted myocardial ischemia-reperfusion injury in rats with type 2 diabetes. Atorvastatin postconditioning alleviated this injury, at least in part, by down-regulating TLR4 and My D88 activation and expression. Therefore, inhibiting TLR4/My D88 signaling pathway might be an appropriate therapy for attenuating ischemia-reperfusion injury. |
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