Effects Of Edaravone On AT₁R/StAR/MR Signaling Pathway In Myocardial Remodeling Mice

Objective:Objective 1:To investigate whether edaravone has a protective effect on myocardial remodeling induced by pressure overload in miceObjective 2:To evaluate the relationship between Edaravone’s inhibition of pressure overload induced myocardial remodeling in mice and angiotensin type 1 receptor（AT₁R）/steroid-synthesised acute regulatory protein（StAR）/salocorticoid receptor（MR）signaling pathways.Methods:24 C57 mice,4 weeks old,weighing 22～24 g,were randomly divided into 4groups（n=6）:control group（C group）,angiotensinⅡ（AngⅡ）group（A group）,Edaravone group（E group）and eplenone group（Ep group）.The mouse myocardial remodeling model was established by subcutaneous microosmotic pump with AngⅡ（1500 ng/（kg·min）for 28 days）.The control group was buried with an osmotic pump prefilled with 0.9%sodium chloride.Group E was given 10mg/（kg·day）Edaravone by intraperitoneal injection for 28 days after subcutaneously embedding a microosmotic pump pre-filled with Ang II.The Ep group was subcutaneously implanted with a microosmotic pump pre-filled with Ang II,and intragastric administration was given100mg（kg·day）of eplenone for 28 consecutive days.After the model was successfully prepared,the hearts of mice were sacrificed and weighed to calculate the ratio of heart weight to body weight（HW/BW）.Myocardial paraffin tissue was collected,the cross-sectional area（MSA）of myocardial cells was determined by HE method,and collagen volume fraction（CVF）was determined by Masson’s staining method.The expressions of AT₁R,StAR,MR,transforming growth factor-β1（TGF-β₁）andα-smooth muscle actin（α-SMA）in myocardial cells were determined by immunohistochemical staining.Results:The HW/BW ratio,MSA and CVF,and the protein expressions of AT₁R,StAR,TGF-β₁,α-SMA and MR In myocardial cells in group A were higher than those in group C,with statistical significance（P<0.05）.The HW/BW ratio,MSA and CVF,and the protein expressions of AT₁R,StAR,TGF-β₁,α-SMA and MR In myocardial cells in group E were lower than those in group A,and the differences were statistically significant（P<0.05）.The HW/BW ratio,MSA and CVF,and the protein expressions of TGF-β₁,α-SMA and MR In myocardial cells in Ep group were lower than those in A group,and the differences were statistically significant（P<0.05）.There was no significant difference in the expression of AT₁R and StAR protein in Ep group compared with group A（P>0.05）.Conclusion:In conclusion,Edaravone can inhibit myocardial remodeling induced by pressure overload in mice,and its mechanism is related to inhibiting the activation of AT₁R/StAR/MR Signaling pathway.