Effects of genistein on neointimal changes after balloon injury of carotid artery in ovariectomized rats

Abstract

The study aim was to investigate the effects of genistein on neointimal changes after balloon injury of carotid artery in ovariectomized rats and its related mechanism. The study aim was to investigate the effects of genistein on neointimal changes after balloon injury of carotid artery in ovariectomized rats and its related mechanism. Female Wistar rats weighing 240-270 g aged 12 weeks old (N=32) were randomly divided into 4 groups:- i) the sham group, n=8, treated with dimethyl sulfoxide (DMSO) 100 µl/day subcutaneously (sc); (control negative group), ii) the ovariectomized rats, n=8, treated with DMSO 100 µl/day, sc (control positive group), iii) the ovariectomized rats, n=8, treated with genistein 0.25 mg/kg/day, sc (experiment group with Gen) and iv) the ovariectomized rats, n=8, treated with 17β-estradiol 0.2 µg/kg/day, sc (experiment group with E2). After four weeks of nurturing, the 24 ovariectomized rats underwent balloon injury of left carotid artery. The left carotid arteries of the 32 rates were harvested two weeks later for histological and immunohistochemical studies. The results showed that the intimal area and the ratio of intimal area to medial area were significantly increased in the control positive group compared with control negative group (2,805.27 ± 168.15 µm², 1.27 ± 0.07 and 1,102.05 ± 29.76 µm², 0.47 ± 0.00 respectively; p<0.005). The intimal area and the ratio of intimal area to medial area were significantly decreased in the experiment group with Gen and the experiment group with E2 as compared with the control positive group (1,762.37± 282.40 µm², 0.76 ± 0.11 and 1,298.00 ± 152.02 µm², 0.58 ± 0.07 respectively; p<0.005). Immunohistochemistry study disclosed that the number of cells expressing inducible nitric oxide synthase (iNOS) and asymmetric dimethylarginine (ADMA) were decreased in the experiment group with Gen and the experiment group with E2 compared with the control positive group (12.5 ± 5.2%, 10 ± 3.7% and 25 ± 5%, 18.7 ± 6.3% respectively compared with control positive, 77.5 ± 7.9%, 82.5 ± 7.9% respectively; p <0.05). In conclusion, the balloon injury significantly led to neointimal changes of carotid arteries in ovariectomized rats. The administration 0.25 mg/kg/day of genistien subcutaneously could inhibit neointimal hyperplasia in association with reduced iNOS and endogenous NOS inhibitor factors, similar to estrogenic action.