1.广安市人民医院心血管内科,四川 广安 638000; 2.重庆医科大学附属第一医院心血管内科,重庆 400016
R-33
1.Department of Cardiology, People’s Hospital of Guangan City, Guang’an 638000, China. 2. Department of Cardiology, the First Affiliated Hospital of Chongqing Medical University, Chongqing 400016
目的 研究七叶皂苷钠( SA) 通过 p38MAPK 通路减少大鼠心肌梗死面积和无复流面积的作用。 方法 成年雄性 SD 大鼠随机分为对照组、缺血再灌注(I/ R)组、I/ R+SA 组、空白腺病毒+I/ R 组、p38MAPK 腺病毒 +I/ R 组、空白腺病毒+I/ R+SA 组、p38MAPK 腺病毒+I/ R+SA 组,采用左冠状动脉前降支结扎的方式建立心肌 I/ R 模型,给予腹腔注射 SA 或心肌局部多点注射腺病毒干预,硫黄素 S 染色检测心肌无复流面积、氯化硝基四氮唑蓝染色检测心肌梗死面积、TUNEL 染色检测心肌细胞凋亡率,酶联免疫吸附法(ELISA)检测白介素-1β(IL-1β)、肿瘤坏死因子-α(TNF-α)、细胞间黏附分子-1(ICAM-1)的含量,Western blot 检测 bcl-2 相关 X 蛋白(Bax)、裂解型含半胱氨酸的天冬氨酸蛋白水解酶-3(cleaved caspase-3)、p-p38MPAK 的表达量。 结果 与 I/ R 组比较,I/ R+SA 组大鼠心肌无复流面积、梗死面积明显缩小,细胞凋亡率、 IL-1β、TNF-α、 ICAM-1 的含量、Bax、Cleaved caspase-3、 p- p38MPAK 的表达量明显减少(P<0. 05);与空白腺病毒+I/ R 组比较,p38MAPK 腺病毒+I/ R 组大鼠心肌无复流面积、梗死面积明显增加,细胞凋亡率、IL-1β、TNF-α、ICAM-1 的含量、Bax、Cleaved caspase-3、p-p38MPAK 的表达量明 显增加(P<0. 05);与空白腺病毒+I/ R+SA 组比较,p38MAPK 腺病毒+I/ R+SA 组大鼠心肌无复流面积、梗死面积明显增加,细胞凋亡率、IL-1β、TNF-α、ICAM-1 的含量、Bax、Cleaved caspase-3、p-p38MPAK 的表达量明显增加( P< 0. 05)。 结论 SA 能够减少大鼠心肌 I/ R 后梗死面积和无复流面积,抑制 p38MAPK 通路介导的炎症反应及细胞凋亡是 SA 发挥上述改善作用相关的分子机制。
Objective To study the mechanism by which sodium aescinate (SA) reduces the areas of myocardial infarction area and no-reflow through the p38MAPK pathway in rats. Methods Adult male Sprague-Dawley rats were randomly divided into seven groups as follows: control, ischemia-reperfusion ( I/ R), I/ R+SA, blank adenovirus+I/ R, p38MAPK adenovirus+I/ R, blank adenovirus+I/ R+SA, and p38MAPK adenovirus+I/ R+SA. The myocardial I/ R model was established by ligating the anterior descending branch of the left coronary artery. Intervention comprised intraperitoneal injection of SA or local injection of adenovirus. Staining was used for detection as follows: thioflavin S for myocardial no- reflow area, nitrotetrazolium chloride blue for myocardial infarction area, and terminal deoxynucleotidyl transferase dUTP nick end labeling for apoptosis. Enzyme-linked immunosorbent assay was used to detect interleukin ( IL-1β), tumor necrosis factor (TNF-α) and intercellular adhesion molecule (ICAM-1). Western blot was used to detect the expression of Bax, cleaved caspase-3 and phosphorylated p38 MAPK (p-p38 MAPK). Results Compared with the I/ R group, the areas of myocardial no reflow and infarct were significantly reduced, and there were significant decreases in the apoptosis rate, contents of IL-1β, TNF-α and ICAM-1, and the expression of Bax, cleaved caspase-3 and p-p38 MAPK (P<0. 05). Compared with the blank adenovirus+I/ R group, the areas of myocardial no reflow and infarct were significantly enlarged, and there were significant increases in the apoptosis rate, contents of IL-1β, TNF-α and ICAM-1, and the expression of Bax, cleaved caspase-3 and p-p38MAPK, in the p38MAPK adenovirus+I/ R group (P<0. 05). Compared with the blank adenovirus+I/ R+SA group, the areas of myocardial no reflow and infarct were significantly enlarged, and the apoptosis rate, contents of IL-1β, TNF-α and ICAM-1, as well as the expression of Bax, cleaved caspase-3 and p-p38MAPK, were significantly increased in the p38MAPK adenovirus+I/ R+SA group (P<0. 05). Conclusions SA reduced the myocardial infarction area and no-reflow area of rats after myocardial I/ R. The molecular mechanism for SA involves inhibition of the p38MAPK pathway to mediate the inflammatory response and apoptosis.
文俊杰,苏 展,罗素新.七叶皂苷钠通过 p38MAPK 通路减少大鼠心肌梗死面积和无复流面积的研究[J].中国比较医学杂志,2021,31(3):8~15.
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