Desenvolvimento e validação de um modelo de endometriose subcutânea em ratas para estudo de prováveis mecanismos fisiopatológicos e do efeito de drogas

Abstract

Endometriosis is defined as the presence of endometrial tissue (gland and stroma) outside the uterus. The objective of this study was to design a model of subcutaneous endometriosis in rats for the evaluation of the effect of drugs and the pathophysiology of endometriosis. Initially, female Wistar rats (Rattus norvergicus) were implanted subcutaneously with 4x4 mm uterine fragments to evaluate endometrioma growth after 1, 7, 14 and 21 days. Endometrial tissue implants were confirmed by histological analysis. The greatest relative weight gain was observed on the 14th day (wet weight 29.17 ± 6.79 mg%; dry weight 5.36 ± 0.97 mg%). Subsequently, animals were assigned to treatment groups and given either estradiol (2.5 mg/kg, 5 mg/kg, 10 mg/kg sc), medroxyprogesterone acetate (0.5 mg/kg, 2 mg/kg, 5 mg/kg sc), triptorelin pamoate (0.18 mg/kg, 0.56 mg/kg sc) and acetylsalicylic acid (3 mg/kg gavage) on the fifth day following implantation. Wet and dry relative weight of the endometrioma were used as a indicator of growth for model of endometriosis. In the group treated with estradiol, the average wet weight and dry weight on the 14 th day following implantation was 36.62 ± 4.97 mg% and 3.97 ± 1 mg% (2.5 mg), 56.37 ± 20.19 mg% and 9.11 ± 3.85 mg% (5 mg), and 173.89 ± 69.53 mg% and 27.67 ± 10.27 mg% (10 mg), respectively. In the group treated with medroxyprogesterone acetate, the corresponding figures were 13.58 ± 2.53 mg% and 2.67 ± 0.5 mg% (0.5 mg), 14.29 ± 2.07 mg% and 3.71 ± 1.31 mg% (2 mg), and 15.33 ± 7.08 mg% and 2.68 ± 1.44 mg% (5 mg). In the group treated with triptorelin pamoate, the corresponding figures were 20.04 ± 4.02 mg% and 5.21 ± 1.54 mg% (0.18 mg), and 10.86 ± 1.88 mg% and 1.89 ± 0.29 mg% (0.56 mg). In the group treated with 3 mg acetylsalicylic acid, the corresponding figures were 12.81 ± 2.04 mg% and 2.09 ± 0.4 mg%. In the estradiol group, growth gain was dose-dependent: animals receiving 10 mg differed significantly from animals receiving lower doses and from untreated animals (p<0.0001). In conclusion, the model was found to be reproducible and easy to use.