The Role And Mechanism Of Steroid Receptor Coactivator 1 (SRC-1) In Angiotensin Ⅱ-Induced Hypertensive Inflammation In Mice

Objective:Hypertension is one of the common diseases of cardiovascular system.It has been shown that hypertension is essentially a chronic inflammatory reactive disease.The SRC family can not only bind to sglucocorticoid receptors,but also assist in the activation of other transcription factors NF-κB and AP-1.As a member of the SRC family,the purpose of this study is whether SRC-1 plays a role by regulating the expression of NF-κB,GR and AP-1 in the animal model of hypertension induced by Ang-Ⅱ.Methods:The wild type and knockout mice were propagated and identified,and the micropumps containing Ang-Ⅱ and normal saline were implanted subcutaneously into the back of the mice.After continuous perfusion of micropump for 28 days,the systolic blood pressure of caudal artery of mice was measured,after confirming that the animal model of hypertension had been successfully established,the animals were dissected and the thoracic aorta of mice was removed.It was divided into three parts,one of which was fixed in 4%paraformaldehyde for hematoxylin-eosin(HE)staining.The expression of inflammatory factors TNF-α,IL-1βand IL-6 was detected by real-time fluorescence quantitative PCR(Real TimePCR)(FQ-PCR).The last part was also put into the cryopreservation tube to detect the expression of NF-κB,GR and AP-1 protein by Western Blot.Results:After 28 days of continuous perfusion with micropump,the systolic blood pressure of caudal artery in Ang-Ⅱ perfusion group was higher than that in saline control group,while that in SRC-1 gene knockout Ang-II perfusion group was significantly higher than that in saline control group.-The results of hematoxylin-eosin(HE)staining showed that the ratio of media thickness and lumen diameter of thoracic aorta in Ang-II perfusion group was higher than that in saline control group,and the ratio of SRC-1 gene knockout Ang-II perfusion group was higher than that in saline control group.Real-time fluorescence quantitative PCR(Real TimePCR)showed that the expression levels of inflammatory factors TNF-α,IL-1β and IL-6 in thoracic aorta of Ang-Ⅱ perfusion group were higher than those of saline control group.Expression of TNF-β,IL-1β and IL-6 in SRC-1 knockout Ang-Ⅱ perfusion group.there’s a more significant increase.The results of Western Blot showed that the protein expression levels of NF-κB,GR and AP-1 in thoracic aorta of Ang-Ⅱ perfusion group were not significantly different from those of saline control group.Conclusion:SRC-1 knockout could aggravate the increase of blood pressure induced by Ang-Ⅱ perfusion in mice,thicken the aortic wall,and up-regulate the mRNA expression of inflammatory factors such as TNF-α,IL-1β and IL-6,which was not related to NF-κB,GR and AP-1.