The Protective Effect Of Formononetin On Vascular Endothelial Cells In Rats And Its Mechanism

Objective: In this study,to investigate the protective effect of formononetin on vascular endothelial cells and its mechanism,we constructed female ovariectomized rat models,then detected the regulation of formononetin on the expression of IGF-1R and ICAM-1 in VECs of rats' uteri,thoracic aortas and breast tissues.It proved that formononetin possessed cardioprotective effect,which provided a theoretical basis for the application of the drug.Methods: 40 healthy adult female SD rats with the body weight of 210±10 g were selected.The rats were equally and randomly divided into 4 groups: Sham group,Ovariectomized(OVX)group,which treated with different doses formononetin(intragastric administration with formononetin 8 mg/kg/d and 16 mg/kg/d).After 40 days treatment,all rats were sacrificed and the uteri,thoracic aortas and breast tissues were separated.qRT-PCR and Western-Blot were used to detect the IGF-1R and ICAM-1 mRNA and protein expression in rats' uteri.Immunohistochemical were also used to detected the IGF-1R and ICAM-1 protein expression in rats' uteri,thoracic aortas and breast tissues.Results: 1.Through statistical analysis,the results showed that the uteri weight in Sham group was larger than that of OVX group.Besides,the uteri weight in formononetin-treated group was also larger than that of OVX group,indicating that formononetin had estrogen-like effects and the uteri grown after administrated with formononetin.2.When compared with Sham group,both of the qRT-PCR and Western-Blot results indicated that mRNA and protein expression level of IGF-1R and ICAM-1 were decreased in OVX group.However,when compared with OVX group,the mRNA and protein expression level of IGF-1R and ICAM-1 were increased in formononetin-treated group.3.Immunohistochemistry results showed that the protein expression level of IGF-1R and ICAM-1 in OVX group were significantly lower than those in Sham group.However,compared with OVX group,the protein expression level of IGF-1R and ICAM-1 on the vascular endothelial cell membrane was enhanced in the drug group,which was consistent with the results of qRT-PCR and Western-Blot.Conclusions: Through regulating the expression of IGF-1R and ICAM-1 in VECs of rats' uteri,thoracic aortas and breast tissues,formononetin can effectively promote endothelial cell proliferation and angiogenesis,thus exerting cardiovascular protection,which provide theoretical basis for the application of formononetin in cardiovascular diseases.