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依达拉奉对心肌重构小鼠AT1R/StAR/MR信号通路的影响

Effects of Edaravone on AT1R/StAR/MR signaling pathway in myocardial remodeling mice
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摘要 目的探究依达拉奉治疗小鼠压力超负荷致心肌重构与血管紧张素1型受体(AT1R)/类固醇合成急性调节蛋白(StAR)/盐皮质激素受体(MR)的关系。方法SPF级C57小鼠18只,4周龄,体重22~24 g,根据随机数字表法将其分为对照组、血管紧张素Ⅱ组、依达拉奉组,每组6只。采用皮下埋置渗透泵持续灌注血管紧张素Ⅱ1500 ng/(kg·min)28 d的方法制备小鼠心肌重构模型。对照组埋置预先充填0.9%氯化钠的渗透泵;依达拉奉组皮下埋置预先充填血管紧张素Ⅱ的渗透泵后,每日给予腹腔注射依达拉奉10 mg/kg,连续28 d。于模型制备成功后,处死小鼠取心脏,称重后计算心重/体重(HW/BW)比值;取心肌石蜡组织切片,采用苏木精-伊红染色法测定心肌细胞横截面积,采用Masson’s染色法测定胶原容积分数(CVF),采用免疫组织化学染色法测定心肌细胞血管紧张素1型受体(AT1R)、StAR、MR、转化生长因子-β_(1)(TGF-β_(1))、α-平滑肌肌动蛋白(α-SMA)表达。结果血管紧张素Ⅱ组小鼠HW/BW比值、MSA和CVF高于对照组,差异有统计学意义(P<0.05);依达拉奉组小鼠HW/BW比值、MSA和CVF低于血管紧张素Ⅱ组,差异有统计学意义(P<0.05)。血管紧张素Ⅱ组小鼠AT1R、StAR、TGF-β_(1)、α-SMA、MR蛋白表达高于对照组,差异有统计学意义(P<0.05);依达拉奉组小鼠AT1R、StAR、TGF-β_(1)、α-SMA、MR蛋白表达低于血管紧张素Ⅱ组,差异有统计学意义(P<0.05)。结论依达拉奉治疗小鼠压力超负荷致心肌重构与抑制AT1R/StAR/MR有关。 Objective To explore the relationship between angiotensinⅡtype 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,angiotensinⅡgroup,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 angiotensinⅡ1500 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 angiotensinⅡosmotic 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-β_(1)(TGF-β_(1))andα-smooth muscle actin(α-SMA)in cardiomyocytes were determined by immunohistochemical staining.Results The HW/BW ratio,MSA and CVF in angiotensinⅡgroup 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 angiotensinⅡgroup,and the differences were statistically significant(P<0.05).The protein expressions of AT1R,StAR,TGF-β_(1),α-SMA,and MR in angiotensinⅡgroup were higher than those in control group,and the differences were statistically significant(P<0.05).The protein expressions of AT1R,StAR,TGF-β_(1),α-SMA,
作者 薛阳阳 秦窈窈 高建辉 岳鸾依 张玮玮 余淑珍 XUE Yangyang;QIN Yaoyao;GAO Jianhui;YUE Luanyi;ZHANG Weiwei;YU Shuzhen(College of Anesthesia,Shanxi Medical University,Shanxi Province,Taiyuan 030001,China;the Fifth Clinical Medical College,Shanxi Medical University,Shanxi Province,Taiyuan 030001,China;Department of Anesthesiology,the Shanxi Medical University Affiliated People’s Hospital,Shanxi Province,Taiyuan 030012,China)
出处 《中国医药导报》 CAS 2023年第24期28-31,共4页 China Medical Herald
基金 山西省回国留学人员科研资助项目(2020-181) 山西省留学人员科技活动项目择优资助项目(晋人社厅函〔2019〕1176号-15)。
关键词 自由基清除剂 心肌重构 血管紧张素Ⅱ1型受体 类固醇合成急性调节蛋白 盐皮质激素受体 Free radical scavengers Myocardial remodeling AngiotensinⅡtype 1 receptor Steroidogenic acute regulatory protein Mineralocorticoid receptors
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