ABSTRACT
Abstract Purpose Patients with diabetes are vulnerable to myocardial I/R (ischaemia/reperfusion) injury, but are not responsive to IPO (ischaemic post-conditioning). We hypothesized that decreased cardiac Adiponectin (APN) is responsible for the loss of diabetic heart sensitivity to IPO cardioprotecton. Methods Diabetic rats were subjected to I/R injury (30 min of LAD occlusion followed by 120 min of reperfusion). Myocardial infarct area was determined by TTC staining. Cardiac function was monitored by a microcatheter. ANP, 15-F2t-isoprostane, nitrotyrosine and MDA were measured by assay kits. Levels of p-Akt, total-Akt and GAPDH were determined by Western Blot. Results Diabetic rats subjected to myocardial IR exhibited severe myocardial infarction and oxidative stress injury, lower APN in the plasma and cardiac p-Akt expression ( P <0.05). IPO significantly attenuated myocardial injury and up-regulated plasma APN content and cardiac p-Akt expression in non-diabetic rats but not in diabetic rats. Linear correlation analysis showed that the expression of adiponectin was positively correlated with p-Akt and negatively correlated with myocardial infarction area ( P <0.01). Conclusion Protective effect of IPO was tightly correlated with the expression of adiponectin, exacerbation of I/R injury and ineffectiveness of IPO was partially due to the decline of adiponectin and inactivation of Akt in diabetes mellitus.
Subject(s)
Animals , Male , Rats , Myocardial Reperfusion Injury/prevention & control , Diabetes Mellitus, Experimental/metabolism , Adiponectin/therapeutic use , Ischemic Postconditioning/methods , Blood Glucose/analysis , Myocardial Reperfusion Injury/metabolism , Rats, Sprague-Dawley , Disease Models, AnimalABSTRACT
A síndrome do ovário policístico é a endocrinopatia ginecológica mais frequente das mulheres em idade reprodutiva, clinicamente caracterizada pela presença de anovulação crônica hiperandrogênica, hirsutismo e infertilidade. Além das alterações reprodutivas, uma proporção considerável das portadoras da síndrome apresenta anormalidades metabólicas como: resistência à insulina e obesidade, com aumento significativo do risco para o desenvolvimento de intolerância à glicose; diabetes mellitus e doença cardiovascular. No entanto, os mecanismos fisiopatológicos que vinculam a obesidade, a resistência à insulina e os demais distúrbios metabólicos presentes na síndrome do ovário policístico ainda não estão completamente esclarecidos. Estudos recentes sugerem que a adiponectina, uma proteína secretada especificamente pelo tecido adiposo, que apresenta propriedades antiaterogênicas, anti-inflamatórias e sensibilizadora à ação da insulina, poderia apresentar um importante papel integrador na patogênese desses distúrbios metabólicos.
Polycystic ovary syndrome is the most common gynecologic endocrinopathy of reproductive age women. It is clinically characterized by hyperandrogenic chronic anovulation, hisrutism and infertility. In addition to reproductive alterations, a significant proportion of polycystic ovary syndrome women display metabolic abnormalities such as insulin resistance and adiposity, predisposing to greater risk of developing glucose intolerance; diabetes mellitus and cardiovascular disease. However, the physiopathologic mechanisms linking obesity, insulin resistance and the other polycystic ovary syndrome metabolic disturbances are not completely understood. Recent studies suggest that adiponectin, a protein specifically secreted by adipose tissue and which has antiatherogenic, anti-inflammatory and insulin-sensitizing properties, could play an important and integrative role in the pathogenesis of these metabolic disturbances.