| Objective:To investigate effects of lipoxinA4 (LXA4) on myocardial ischemia/reperfusion injury in type 1 diadetic rats and explore the potential mechanisms.Methods:Sixty male Sprague-Dawley rats, weighting 220-250 g, were randomly divided into six groups (n=10 per group):non-diabetic sham operation group (NS), diabetic sham operation group (DS), non-diabetic myocardial ischemia/reperfusion group (NI/R), diabetic myocardial ischemia/reperfusion group (DI/R), non-diabetic lipoxinA4 group (NLX) and diabetic lipoxinA4 group (DLX). Type 1 diabetic mellitus were induced by single intraperitoneal streptozotocin injection (55 mg/kg). Rats in non-diabetic groups were injected with equal volume citrate buffer liquid into the abdominal cavity as control. Myocardial ischemia/reperfusion model was induced by occluding the left anterior descending branch of coronary artery for 30 min followed by 240 min reperfusion when the type 1 diabetic model was successfully established for one week. In detail, rats in NS and DS groups underwent a similar operation without ischemia and reperfusion for 270 min; rats in NI/R and DI/R groups received normal saline 1 ml/rat 5 min before ischemia; rats in NLX and DLX groups received LXA4 2.5 μg/kg 5 min before ischemia. The blood glucose, body weight and general condition of rats were observed carefully. The cardiac pathological changes were observed through HE staining under a light microscope. And the serum concentration of tumor necrosis factor-α (TNF-α), the number of apoptotic myocardial cells, and the expression of Caspase-3, Bcl-2 and Bax were measured.Results:The blood glucose of diabetic rats was significantly higher than non-diabetic rats, however the body weight was lower than non-diabetic rats (P < 0.05). Compared with the baseline level, the blood glucose of diabetic rats showed a marked increase (P<0.05), while body weight barely grew (P>0.05). After reperfusion, the cardiac pathological changes in NI/R group and DI/R group included a large number of disarrayed and irregularly myocardial fibers, and the lost of cross striations. The cardiomyocytes showed swelling, and some of which were dissolved. Lots of red blood cells and inflammatory cells also were found between the cardiomyocytes. And more inflammatory cells in DI/R group were observed. The injuries of the myocardium in NLX group and DLX group lightened significantly. The serum concentration of TNF-α and the apoptosia index (AI) in DS group, NI/R group, DI/R group, NLX group and DLX group were increased when compared with NS group, respectively (P< 0.05). Both the serum concentration of TNF-α and the AI in NLX group were lower than those in NI/R group, instead, those two indexs in DI/R group were higher (P< 0.05). Compared with DI/R group, the serum concentration of TNF-α and the AI in DLX group reduced significantly (P< 0.05). The Caspase-3 mRNA and protein levels of DS group increased markedly when compared with NS group, as well as the Caspase-3, Bcl-2, Bax mRNA and protein levels of NI/R group, DI/R group, NLX group and DLX group (P< 0.05). Compared with NI/R group, significant decrease of Caspase-3 and Bax mRNA and protein expression, and increase of Bcl-2 mRNA and protein expression were revealed in NLX group, while an inrease of Caspase-3 mRNA and protein levels was also observed in DI/R group (P< 0.05). The levels of Caspase-3, Bax mRNA and protein in DLX group were lower, on the contrary, the Bcl-2 mRNA and protein levels was higher than those in DI/R group (P< 0.05).Conclusions:The myocardial ischemia/reperfusion injury had been deteriorated by type 1 diabetes even at early stage. Treatment with lipoxinA4 could decrease the surm concentration of TNF-a, down-regulate Caspase-3 and Bax levels, and up-regulate Bcl-2 levels, subsequently reduced the inflammatory response and myocardial apoptosis, and these may finally help to protect myocardium from injuries. |
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