沙库巴曲缬沙坦对腹主动脉缩窄法致大鼠心肌纤维化的影响  

Effects of sacubitril/valsartan on myocardial fibrosis induced by abdominal aortic constriction in rats

作　　者：李松海 韩俊 欧阳斐 冮洪生 Li Songhai;Han Jun;Ouyang Fei;Gang Hongsheng(Department of Cardiology,Wuhan Fourth Hospital,Wuhan 430033,Hubei Province,China)

机构地区：[1]武汉市第四医院心内科,430033

出　　处：《中华老年心脑血管病杂志》2025年第3期364-369,共6页Chinese Journal of Geriatric Heart,Brain and Vessel Diseases

基　　金：武汉市医学科研究项目(WX20C06)。

摘　　要：目的探讨沙库巴曲缬沙坦对腹主动脉缩窄法(abdominal aortic constriction,AAC)致大鼠心肌纤维化(myocardial fibrosis,MF)及miR-21表达的影响。方法选择SPF级雄性SD大鼠72只,随机分为假手术组、AAC组、沙库巴曲缬沙坦低剂量组、沙库巴曲缬沙坦高剂量组、沙库巴曲缬沙坦高剂量+agomiR-NC组、沙库巴曲缬沙坦高剂量+miR-21-agomiR组,每组12只。超声心动图进行心功能检测,苏木精-伊红染色检测心肌组织病理变化;马松染色检测心肌组织纤维化情况;免疫组织化学检测心肌组织α-平滑肌动蛋白(alpha-smooth muscle actin,α-SMA)、Ⅰ型胶原(typeⅠcollagen,COL-1)表达;实时荧光定量聚合酶链反应检测miR-21水平。结果与假手术组比较,AAC组心肌纤维变粗且断裂明显,排列紊乱,心肌细胞肥大且核固缩深染,大量炎性细胞浸润,MF明显,左心室舒张末期内径(left ventricular end-diastolic diameter,LVEDD)、左心室收缩末期内径(left ventricular end-systolic diameter,LVESD)、miR-21水平及α-SMA、COL-1表达升高,左心室射血分数(left ventricular ejection fraction,LVEF)、左心室缩短分数(Left ventricular shortening fraction,LVFS)水平降低(P<0.05);与AAC组比较,沙库巴曲缬沙坦低剂量组、沙库巴曲缬沙坦高剂量组心肌纤维排列相对整齐,纹理清晰,分布均匀,变粗断裂现象减少,心肌细胞相对正常,炎性细胞浸润现象减轻,心肌纤维程度减轻,LVEDD、LVESD、miR-21水平及α-SMA、COL-1表达降低,LVEF、LVFS水平升高(P<0.05);与沙库巴曲缬沙坦高剂量+agomiR-NC组比较,沙库巴曲缬沙坦高剂量+miR-21-agomiR组心肌纤维排列紊乱,心肌纤维变粗、断裂现象加剧,心肌细胞异常,炎性细胞浸润明显,MF加剧,LVEDD、LVESD、miR-21水平及α-SMA、COL-1表达升高,LVEF、LVFS水平降低[(7.11±0.45)mm vs(6.05±0.38)mm,P<0.05;(5.58±0.35)mm vs(4.01±0.28)mm,P<0.05;2.57±0.14 vs 0.98±0.10,P<0.05;(0.62±0.06)A vs(0.41±0.04)A,P<0.05;(0.79±0.08)A vsObjective To investigate the effects of SAC/VAL on myocardial fibrosis and miR-21 expression in rats induced by AAC.Methods A total of 72 SPF SD male rats were randomly divided into sham operation group,AAC group,low-and high-dose SAC/VAL groups,high-dose SAC/VAL+agomiR-NC group,and high-dose SAC/VAL+miR-21 agomiR group,with 12 rats in each group.Echocardiography was used to test cardiac function.HE staining and Masson staining were applied to observe the pathological changes in myocardial tissues and myocardial tissue fibrosis,respectively.Immunohistochemical assay was employed to detect the expression ofα-SMA and COL-1 in myocardial tissue.Real-time fluorescence quantitative polymerase chain reaction was conducted to detect miR-21 level.Results Compared with the sham operation group,the AAC group had thicker and broken myocardial fibers in disordered arrangement,hypertrophic myocardial cells with condensed and deeply stained nuclei,and extensive infiltration of inflammatory cells,and obvious myocardial fibrosis,increased LVEDD and LVESD values,and up-regulated miR-21,α-SMA and COL-1 expression,but decreased LVEF and LVFS levels(P<0.05).Lowand high-dose SAC/VAL treatment resulted in well-arranged less broken myocardial fibers in uniform distribution,relatively normal myocardial cells,less inflammatory cell infiltration,and reduced severity of myocardial fibers,lower LVEDD and LVESD values,decreased miR-2l,α-SMA and COL-1 levels,but increased LVEF and LVFS levels when compared to the AAC group(P<0.05).When compared to the high dose SAC/VAL+agomiR NC group,the high-dose SAC/VAL+miR-21 agomiR group had disorderly-arranged myocardial fiber with thickening and breakage,aberrant myocardial cells,obvious infiltration of inflammatory cells,and intensified myocardial fibrosis,higher LVEDD and LVESD values and miR-21,α-SMA and COL-1 expression levels,and lower LVEF and LVFS levels[7.11±0.45 mm us 6.05±0.38 mm,P<0.05;5.58±0.35 mm vs 4.01±0.28 mm,P<0.05;2.57±0.14 vs 0.98±0.10,P<0.05;0.62±0.06 A vs 0.41±0.04 A,P<

关 键 词：主动脉 腹 大鼠 心肌疾病 心脏功能试验 

分 类 号：R542.23[医药卫生—心血管疾病]