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

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、pp38MPAK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。

Sodium aescinate reduces myocardial infarction area and no-reflow area of rats through the p38MAPK pathway

Objective To study the mechanism by which sodium aescinate(SA)reduces the areas of myocardial infarction area and no-reflow through the p38 MAPK 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,p38 MAPK adenovirus+I/R,blank adenovirus+I/R+SA,and p38 MAPK 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 noreflow area,nitrotetrazolium chloride blue for myocardial infarction area,and terminal deoxynucleotidyl transferase d UTP 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-αand 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-αand ICAM-1,and the expression of Bax,cleaved caspase-3 and p-p38 MAPK,in the p38 MAPK 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-αand ICAM-1,as well as the expression of Bax,cleaved caspase-3 and p-p38 MAPK,were significantly increased in the p38 MAPK 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 p38 MAPK pathway to mediate the inflammatory response and apoptosis.