| خلاصه مقاله | Introduction: Several evidences indicate that inhibition of angiogenesis can be a productive therapeutic strategy in inflammatory diseases. A bidirectional interaction between the nervous and immune systems was becoming increasingly well documented. The aim of the present study was to evaluate the effect of opioidergic system on the inflammatory angiogenesis in a rat model for rheumatoid arthritis, namely air pouch model of inflammation.
Materials and Methods: Male wistar rats (200-250 g) were anesthetized; sterile air (20 ml and 10 ml) was injected subcutaneously on the back on day 1 and day 3 respectively. On day 6, inflammation was induced by injection of carrageenan into air pouches. Saline as control and naloxone (100, 200,400 and 800 µg) were administered intra pouch at the same time as the carrageenan and then for 2 consecutive days. After 72h, the rats were sacrificed and the pouches were opened; its fluid was collected in order to determine VEGF and IL1β level (as angiogenesis markers). The granulation tissues formed were dissected, washed in PBS and cut into small pieces before being homogenized. The tissue homogenates were centrifuged and the supernatants were filtered through a 0.22µ filter. The hemoglobin concentration in the supernatant was then determined spectrophotometrically using a hemoglobin assay kit.
Results: Naloxone with doses of 200 and 800 µg decreased (p < 0.001) tissue hemoglobin concentration (393.1±26.7 & 378.5±66.9 mg/100g tissue, respectively) versus the control group (937±139.8 mg/100 g tissue). The VEGF level of exudate by naloxone-treated rats (800 & 100 µg, p< 0.001) and (200 & 400 µg, p< 0.01) was significantly decreased in a bell-shaped dose response manner. In addition, there was a significant reduction in the IL1β level with the same dose response manner.
Conclusion: The current study highlights evidences for the promising anti-angiogenesis effects of naloxone that could be mediated through attenuation of IL1β and VEGF concentrations. The appearance of bell-shaped reversal curve is unknown, but probably reflects the complex pharmacology of opioids and may be related to the existence of different opioid receptor subtypes, some mediating the effects of naloxone at low dose, the others mediating antagonistic effects at high dose. |