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卡格列净减轻心肌梗死后细胞凋亡及炎症反应改善预后

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目的 探究在心肌梗死(MI)后使用卡格列净(CANA)对心脏炎症反应及细胞凋亡的作用。方法 选用15只8~10周龄C57/BL6小鼠(SPF级),用抽签法随机抽取5只小鼠为Sham组(假手术+生理盐水灌胃),剩余10只小鼠通过结扎左冠状动脉前降支的方法制作MI模型,制作成功后的10只MI小鼠随机分为2组:MI组(生理盐水灌胃)、CANA+MI组(CANA灌胃),每组5只。CANA+MI组小鼠以20 mg/(kg·d-1)卡格列净灌胃4周,Sham组及MI组则使用同等体积生理盐水灌胃4周。4周后,使用小鼠超声机测量左室收缩末期内径及左室射血分数。苏木精染色、Tunel染色用于明确心脏结构及MI后细胞凋亡状况。IF免疫荧光染色用于检测MI后心脏炎症反应程度。Western blotting用于检测炎症及凋亡相关蛋白表达水平。结果 与MI组相比,CANA+MI组左室射血分数升高、梗死面积减小。Tunel染色显示,CANA+MI组小鼠MI边缘区凋亡细胞数量较MI组显著减少,相应促凋亡蛋白Bax表达降低,抑凋亡蛋白Bcl-2表达升高。CANA+MI组小鼠CD3+T细胞、F480+巨噬细胞和LY6G+中性粒细胞数量较MI组明显减少,相关蛋白p-P65、p-IκBα表达量明显降低。结论 CANA抑制了 MI后心脏炎症反应,减轻了细胞凋亡。
Canagliflozin Alleviates Apoptosis and Inflammation After Myocardial Infarction and Improves Prognosis
Objective To investigate the effect of canagliflozin(CANA)on cardiac inflammatory response and apoptosis after myocardial infarction(MI).Methods This study selected 15 C57/BL6 mice(SPF grade)aged 8~10 weeks,and randomly selected 5 mice as the Sham group(sham surgery+saline gavage)using a lottery method.The remaining 10 mice were used to create an MI model by ligating the anterior descending branch of the left coronary artery.After successful production,the 10 MI mice were randomly divided into two groups:the MI group(saline gavage)and the CANA+MI group(Canagliflozin gavage),with 5 mice in each group.The mice in the CANA+MI group were gavaged with 20 mg/(kg·d-1)of Canagliflozin for 4 weeks,while the Sham and MI groups were gavaged with the same volume of physiological saline for 4 weeks.After 4 weeks,left ventricular end systolic diameter and left ventricular ejection fraction were measured using a mouse ultrasound machine.Hematoxylin(HE staining)and Tunel staining are used to clarify the cardiac structure and cell apoptosis status after MI.IF immunofluorescence staining is used to detect the degree of cardiac inflammatory response after MI.Western blotting is used to detect the expression levels of inflammation and apoptosis related proteins.Results Compared with the MI group,left ventricular ejection fraction increased and infarct size decreased in CANA+MI group.Tunel staining showed that the number of apoptotic cells in the MI margin area of the CANA+MI group mice was significantly reduced compared to the MI group,with a corresponding decrease in the expression of pro apoptotic protein Bax and an increase in the expression of anti apoptotic protein Bcl-2.The number of CD3+T cells,F480+macrophages,and LY6G+neutrophils in the CANA+MI group mice was significantly reduced compared to the MI group,with associated proteins p-P65,p-IκBα.The expression level was significantly reduced.Conclusion Canagliflozin inhibits cardiac inflammatory response after MI and reduces cell apoptosis.

CanagliflozinInflammatory responseMyocardial infarctionApoptosis

李铭、高继先、吴冰、刘小熊、夏豪

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武汉大学人民医院心内科 武汉大学心血管病研究所 心血管病湖北省重点实验室,湖北武汉 430060

卡格列净 炎症反应 心肌梗死 细胞凋亡

国家科技支撑计划国家自然科学基金

2015BAI08B0181900364

2024

心血管病学进展
成都市心血管病研究所,成都市第三人民医院

心血管病学进展

CSTPCD
影响因子:0.932
ISSN:1004-3934
年,卷(期):2024.45(4)