Steiner Marcelo Luis, Theodoro Thérèse Rachell, Garcia Shirley Gimenez, Mader Ana Maria Amaral Antonio, Pompei Luciano de Melo, Pinhal Maria Aparecida da Silva, Fernandes César Eduardo
Department of Gynecology and Obstetrics, Faculdade de Medicina do ABC, Santo André, SP, Brazil.
Department of Biochemistry, Faculdade de Medicina do ABC, Santo André, SP, Brazil.
Rev Bras Ginecol Obstet. 2019 Jul;41(7):449-453. doi: 10.1055/s-0039-1693681. Epub 2019 Jul 25.
To analyze the effects of estrogen alone or in combination with progestogens and tibolone (TIB) on the expression of the extracellular matrix metalloproteinases 2 and 9 (MMP-2 and MMP-9), of perlecan, and of heparanase (HPSE) of the vascular walls of the carotid arteries.
A total of 30 250-day-old ovariectomized Wistar rats were orally treated for 5 weeks with: a) 1 mg/kg of estradiol benzoate (EB); b) EB + 0.2 mg/kg of medroxyprogesterone acetate (MPA); c) EB + 0.2mg/kg of norethisterone acetate (NETA); d) EB + 2 mg/kg of dydrogesterone (DI); e) 1 mg/kg of TIB; f) placebo (CTR). Following treatment, the expression of mRNA for MMP-2, MMP-9, and HPSE was analyzed by real-time polymerase chain-reaction (PCR), and the expression of MMP-2, of MMP-9, of tissue inhibitor of metalloproteinase 2 (TIMP-2), and of perlecan was quantified by immunohistochemistry in the carotid arteries.
The groups showed significant differences on mRNA HPSE expression ( = 0.048), which was higher in the EB, EB + MPA, and TIB groups. There was no statistically significant difference in mRNA MMP-2 or MMP-9 expression. The immunohistochemical expression of MMP-2, of TIMP-2, of MMP-9, of HPSE, and of perlecan showed no differences between groups.
Estradiol alone or associated with MPA and TIB treatment can increase mRNA HSPE expression of the walls of the carotid arteries in ovariectomized rats.
分析单独使用雌激素或与孕激素及替勃龙（TIB）联合使用对颈动脉血管壁细胞外基质金属蛋白酶2和9（MMP - 2和MMP - 9）、基底膜聚糖和乙酰肝素酶（HPSE）表达的影响。
总共30只250日龄的去卵巢Wistar大鼠接受为期5周的口服治疗，治疗方案如下：a）1mg/kg苯甲酸雌二醇（EB）；b）EB + 0.2mg/kg醋酸甲羟孕酮（MPA）；c）EB + 0.2mg/kg醋酸炔诺酮（NETA）；d）EB + 2mg/kg地屈孕酮（DI）；e）1mg/kg替勃龙（TIB）；f）安慰剂（CTR）。治疗后，通过实时聚合酶链反应（PCR）分析MMP - 2、MMP - 9和HPSE的mRNA表达，并通过免疫组织化学法定量分析颈动脉中MMP - 2、MMP - 9、金属蛋白酶组织抑制剂2（TIMP - 2）和基底膜聚糖的表达。
各组在mRNA HPSE表达上存在显著差异（P = 0.048），EB组、EB + MPA组和TIB组的表达较高。MMP - 2或MMP - 9的mRNA表达无统计学显著差异。MMP - 2、TIMP - 2、MMP - 9、HPSE和基底膜聚糖的免疫组织化学表达在各组之间无差异。
单独使用雌二醇或与MPA和TIB联合治疗可增加去卵巢大鼠颈动脉壁的mRNA HSPE表达。
