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| Effects of Edaravone on AT1R/StAR/MR signaling pathway in myocardial remodeling mice |
| XUE Yangyang1 QIN Yaoyao1 GAO Jianhui1 YUE Luanyi2 ZHANG Weiwei3 YU Shuzhen3 |
1.College of Anesthesia, Shanxi Medical University, Shanxi Province, Taiyuan 030001, China;
2.the Fifth Clinical Medical College, Shanxi Medical University, Shanxi Province, Taiyuan 030001, China;
3.Department of Anesthesiology, the Shanxi Medical University Affiliated People’s Hospital, Shanxi Province, Taiyuan 030012, China
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Abstract Objective To explore the relationship between angiotensin Ⅱ type 1 receptor (AT1R)/ steroidogenic acute regulatory protein (StAR)/ mineralocorticoid receptor (MR) and myocardial remodeling induced by pressure overload in mice treated with Edaravone. Methods Eighteen SPF grade C57 mice, aged four weeks and weighing 22-24 g, were divided into control group, angiotensin Ⅱ group, and Edaravone group according to random number table method, with six mice in each group. The mouse myocardial remodeling model was prepared by continuous infusion of angiotensin Ⅱ 1 500 ng/(kg·min) with a subcutaneous osmotic pump for 28 days. The control group was implanted with an osmotic pump pre-filled with 0.9% sodium chloride; the edaravone group was given intraperitoneal injection of 10 mg/kg of Edaravone per day for 28 days after subcutaneous implantation of a prefilled angiotensin Ⅱ osmotic pump. 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). Paraffin sections of myocardium were taken, and the cross-sectional area of cardiomyocytes was determined by hematoxylin-eosin staining, and collagen volume fraction was determined by Masson’s staining. The expressions of angiotensin type 1 receptor (AT1R), steroid-synthesized acute regulatory protein (StAR), salocorticoid receptor (MR), transforming growth factor-β1(TGF-β1) and α-smooth muscle actin (α-SMA) in cardiomyocytes were determined by immunohistochemical staining. Results The HW/BW ratio, MSA and CVF in angiotensin Ⅱ group were higher than those in control group, and the differences were statistically significant (P＜0.05). The HW/BW ratio, MSA, and CVF in Edaravone group were lower than those in angiotensin Ⅱ group, and the differences were statistically significant (P＜0.05). The protein expressions of AT1R, StAR, TGF-β1, α-SMA, and MR in angiotensin Ⅱ group were higher than those in control group, and the differences were statistically significant (P＜0.05). The protein expressions of AT1R, StAR, TGF-β1, α-SMA, and MR in Edaravone group were lower than those in angiotensin Ⅱ group, and the differences were statistically significant (P＜0.05). Conclusion The myocardial remodeling induced by pressure overload in mice treated with Edaravone is related to the inhibition of AT1R /StAR/MR.
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