Papel da estimulação colinérgica na inflamação no infarto do miocárdio experimental

• Autor(a) principal: Bezerra, Otávio Coelho
• Data de Publicação: 2015
• Tipo de documento: Dissertação
• Idioma: por
• Título da fonte: Biblioteca Digital de Teses e Dissertações da Uninove
• Texto Completo: http://bibliotecatede.uninove.br/handle/tede/3325
• topic: infarto do miocárdio; inflamação; neuroimunomodulação; via anti-inflamatória colinérgica; ratos wistar; myocardial infarction; inflammation; neuroimmunomodulation; cholinergic anti-inflammatory pathway; wistar; CIENCIAS DA SAUDE

Introduction: The inflammatory process after a myocardial infarction (MI) is necessary for tissue repair, but if that response is insufficient or exacerbated, the patient may have severe clinical manifestations. The modulation of inflammation to suppress the heightened responses, shown a promising therapeutic target. Previous studies have shown that the immune response can be modulated with the actions of the parasympathetic nervous system, by a reflex called "cholinergic anti-inflammatory reflex". Several means can be used to modulate this reflection, as the use of drugs. The pyridostigmine bromide is a potent anticholinesterase that has been used by our group and indicates improvements in functional and morphological studies in inflammatory states after cardiac injury. Objective: To evaluate whether the administration of pyridostigmine bromide modify the concentration of pro-inflammatory cytokines (interleukin 1-β, interleukin-6 and TNF-α) and anti-inflammatory (Interleukin 10) and changes the populations of T reg cells and macrophages (M1 and M2) in cardiac tissue damaged after MI in rats. Methods: Adult male rats (Wistar), weighing 200 to 250, were used and divided into control group (CS), untreated infarcted group (IC) and infarcted treated group (IP) Myocardial infarction was performed by ligation of the left coronary artery, the IP group piridosigmina and immediately treated with a dose of 40 mg / kg / day in the supplied water. On the fifth day, all animals underwent cannulation of the femoral artery for blood pressure (BP) recording the next day, thereby extracting the components of heart rate variability (HRV). On the seventh day the animals were killed specifically for the collection of tissue and measurement of cytokines by ELISA and immunohistochemistry achievement. The results of parametric behavior were analyzed by variance (ANOVA) of a road, while the results of non-parametric behavior were analyzed by Kruskal-Wallis test. Result: The diastolic blood pressure of IP group (83 ± 0.3 mmHg) was similar to the CS group (82 ± 0.9 mmHg), and was higher in the HF group (88 ± 0.3 mmHg). Greater vagal modulation in the IP group was observed when compared to the HF group, because there was an improvement in the low frequency (LF) component (14.7 ± 1.0 vs 28.7 ± 5.0 nu) and in the high frequency (HF) componte (85.4 ± 1,0 un vs 17.2 ± 5.0 nu) of heart rate variability. Moreover, the LF and HF values were similar between IP groups (16.8 ± 3.0 and 83.2 ± 3.0 nu) and CS (14.7 ± 1.0 and 85.4 ± 1.0 nu). The LF / HF ratio in the CS group (0.2 ± 0.05) and IP (0.2 ± 0.05) were also similar, whereas in the HF group was high (0.4 ± 0.09). The concentration of the inflammatory pro-cytokine were higher in HF group compared to the group IP, IL-1β (81 ± 29 vs. 21.8 ± 29,5,6 pg/ml), IL-6 (99 ± 50 vs 26.6 ± 22.4 pg/ml) TNF-α (99 ± 11 vs. 26.6 ± 2.4 pg/ml) and IL-10 (66 ± 6.8 vs 43 ± 3.0 pg/ml), and the PI values were similar to the CS group. Immunohistochemical analysis demonstrated that macrophages (MO) M1 marked on the IP group showed a distribution pattern different in lesion area of the IC group, being more concentrated at the edge of the infarcted tissue. Moreover, MO M2 IP group were higher on the seventh day after MI compared to the IP. Conclusion: We observed that the administration of pyridostigmine anticholinesterase influences the mobilization of inflammatory cells in the infarcted area, reducing macrophage ratio M1 / M2, with significant reduction in concentrations of proinflammatory cytokines in cardiac tissue of rats, on the 7th day Pos IM.