机构地区:[1]徐州市中心医院心内科,221009 [2]徐州市中心医院检验科,221009 [3]南京医科大学第二附属医院心内科
出 处:《中华心血管病杂志》2017年第11期963-970,共8页Chinese Journal of Cardiology
基 金:国家自然科学基金[81170102(BA11)]
摘 要:目的探讨五味子乙素对心肌梗死小鼠心肌结构和心功能的影响及其机制。 方法C57BL/6J雄性小鼠56只,由南京医科大学动物中心提供。采用随机数字表法将小鼠分为3组,即假手术组(n=8)、五味子乙素组(n=24)和心肌梗死组(n=24)。采用冠状动脉结扎术建立小鼠心肌梗死模型,假手术组只开胸不结扎。术后五味子乙素组小鼠给予五味子乙素80 mg·kg-1·d-1灌胃治疗。术后3周观察各组小鼠存活率,通过二维超声心动图检测各组小鼠心功能指标,处死小鼠计算心脏质量/体重比,通过氯化三苯基四氮唑染剂(TTC)和伊文思蓝染色计算心肌梗死面积,制作心脏病理切片并行HE及Masson染色以观察小鼠心肌炎性浸润、结构及纤维化的情况,通过免疫荧光法检测小鼠缺血心肌组织细胞凋亡情况,通过酶联免疫吸附试验检测转化生长因子-β(TGF-β)、肿瘤坏死因子-α(TNF-α)、白细胞介素1β(IL-1β)蛋白的表达水平,Western blot法检测核因子-κB (NF-κB)、B淋巴细胞瘤-2(Bcl-2)相关蛋白X(Bax)、Bcl-2、内皮型一氧化氮合酶(eNOS)、磷酸化eNOS(p-eNOS)、蛋白激酶B (Akt)、磷酸化Akt(p-Akt)蛋白的表达水平。 结果术后3周,假手术组小鼠存活率为100%(8/8),五味子乙素组小鼠存活率为83.33%(20/24),心肌梗死组小鼠存活率为54.17%(13/24),五味子乙素组小鼠存活率明显高于心肌梗死组(P〈0.05)。五味子乙素组小鼠左心室舒张末期内径(LVEDD)和左心室收缩末期内径(LVESD)均明显低于心肌梗死组[分别为(4.13±0.40) mm比(4.44±0.46) mm和(3.07±0.39) mm比(3.46±0.52) mm),P均〈0.05],左心室射血分数(LVEF)和左心室短轴缩短率(LVFS)均明显高于心肌梗死组[(51.77±8.50)%比(40.23±8.30)%和(26.44±5.15)%比(19.53±4.56)%,P均〈0.ObjectiveTo investigate whether Schisandrin B (Sch B) could improve cardiac structure and function in myocardial infarction (MI) mice and related mechanisms. MethodsMale C57BL/6J mice were randomized into sham (n=8), MI+ Sch B (n=24, 80 mg·kg-1·d-1 per gavage) or MI+ vehicle (n=24, equal volume). After treatment for 3 weeks, cardiac function was detected by echocardiography measurement.Infarction size was measured by Evans blue and TTC staining.HE and Masson trichrome staining were used to observe the myocardial inflammation, structure and fibrosis.TNF-α, TGF-β, IL-1β were detected by ELISA. The apoptosis index of ischemic myocardial cells was detected by immunofluorescence. NF-κB, Bcl-2, Bax, Akt phosphorylated Akt(p-Akt), eNOS, phosphorylated eNOS (p-eNOS) were detected by Western blot. ResultsThree weeks after operation, survival rate (83.33% vs. 54.17%, P〈0.05), LVEF((51.77±8.50)% vs.(40.23±8.30)%, P〈0.05), LVFS((26.44±5.15)% vs. (19.53±4.56)%, P〈0.05)were significantly higher; LVEDD ((4.13±0.40) mm vs.(4.44±0.46)mm, P〈0.05), LVESD((3.07±0.39) mm vs. (3.46±0.52)mm, P〈0.05), the heart weight/body weight ratio((0.59±0.06)% vs. (0.68±0.10)%, P〈0.05)was significantly lower and infarct size ((23.4±2.36)% vs. (39.4±2.06)%, P〈0.05) was significantly reduced in MI+ Sch B group than those in MI+ vehicle group. In MI+ vehicle group, HE staining showed a large number of inflammatory cells in the peri-infarctl region, and the permutation structure was very disorganized, while above changes were significantly reduced in the MI+ Sch B group. Masson staining results showed that the degree of myocardial fibrosis in MI+ Sch B group was significantly less than that of MI+ vehicle group.Moreover, Sch B could down-regulate some inflammatory cytokines, like NF-κB、TGF-β、TNF-α and IL-1β, activate Akt-eNOS pathway, upgrade Bcl-2 and downgrade Bax and reduce cell apoptosis a
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