红景天苷通过抑制PI3K/AKT/GSK3β通路对AMI后心衰大鼠ColⅠ和Profilin-1蛋白表达的影响

Effects of salidroside on the expression of ColⅠ and Profilin-1 in rats with heart failure after AMI by inhibiting PI3K/AKT/GSK3β

目的探究红景天苷通过抑制PI3K/AKT/GSK3β通路对急性心肌梗死(AMI)后心衰大鼠胶原蛋白I(ColⅠ)、前纤维蛋白-1(Profilin-1)蛋白表达的影响。方法45只SD大鼠随机分为3组(n=15),假手术组,模型组和红景天苷组。模型组和红景天苷组建立AMI后心力衰竭模型,红景天苷组大鼠使用红景天苷灌胃干预。通过心电图和血清B型脑钠肽(BNP)、血管紧张素Ⅱ(AngⅡ)水平评估心衰情况。HE染色和Masson染色检测心肌组织变化和纤维化情况。分别使用Western blot和qRT-PCR检测PI3K/AKT/GSK3β通路和Col I、Profilin-1表达水平。结果模型组大鼠血清BNP、AngⅡ水平显著高于假手术组,并且BNP水平均高于100 pg/ml;红景天苷组的血清BNP、AngⅡ水平显著低于模型组。模型组心肌细胞形状发生改变,排列紊乱,细胞间系变小,出现炎性反应,并出现纤维化状态。红景天组细胞排列异常、炎性反应及纤维化情况均较轻。模型组出现大量的纤维化组织,红景天苷组的纤维化情况显著低于模型组。与假手术组比较,建模后大鼠心肌组织中ColI和Profilin-1的表达水平均显著升高,红景天苷组的ColI和Profilin-1蛋白和mRNA水平均显著低于模型组;建模后大鼠心肌组织中PI3K/AKT/GSK3β通路蛋白磷酸化水平显著升高,红景天组的大鼠心肌组织中p-PI3K/PI3K、p-AKT/AKT、p-GSK3β/GSK3β水平显著低于模型组。结论红景天苷通过抑制PI3K/AKT/GSK3β通路中蛋白的磷酸化,抑制AMI后心力衰竭大鼠心肌组织中ColⅠ、Profilin-1蛋白表达,减轻心肌纤维化水平,减轻心力衰竭。

Objective To investigate the effects of salidroside on the expression of type I collagen(Col I)and Profilin-1 in rats with heart failure after acute myocardial infarction(AMI)by inhibiting PI3K/AKT/GSK3βpathway.Methods Forty-five SD rats were randomly divided into 3 groups(n=15),including the sham operation group,the model group and the salidroside group.The model group and the salidroside group established a model of heart failure after AMI,and the rats in the salidroside group were treated with salidroside.Heart failure was assessed by electrocardiogram and serum B-type brain natriuretic peptide(BNP)and angiotensinⅡ(AngⅡ)levels.HE staining and Masson staining were used to detect myocardial tissue changes and fibrosis.The expression levels of PI3K/AKT/GSK3βpathway,Col I and Profilin-1 were detected by Western blot and qRT-PCR,respectively.Results The serum levels of BNP and AngⅡin the model group were significantly higher than those in the sham operation group,and the BNP level was higher than 100 pg/ml.Serum BNP and AngII levels in the salidroside group were significantly lower than those in the model group.The shape of the myocardial cells in the model group changed,the arrangement was disordered,the intercellular line became smaller,the inflammatory reaction occurred,and the fibrosis state appeared.The cells in the Rhodiola group had abnormal arrangement of cells,inflammatory reaction and fibrosis.There is a large amount of fibrotic tissue in the model group.The fibrosis of the salidroside group was significantly lower than that of the model group.The expression levels of ColI and Profilin-1 in rat myocardial tissue were significantly increased after modeling.The levels of ColI and Profilin-1 protein and mRNA in the salidroside group were significantly lower than those in the model group.The phosphorylation level of PI3K/AKT/GSK3βpathway protein was significantly increased in rat myocardial tissue after modeling.The levels of p-PI3K/PI3K,p-AKT/AKT,and p-GSK3β/GSK3βin the myocardial tissue of the Rhodiola group were significantly lower than those in the model group.Conclusion Salidroside inhibits the expression of ColI and Profilin-1 in myocardial tissue of rats with heart failure after AMI by inhibiting the phosphorylation of the protein in the PI3K/AKT/GSK3βpathway,reducing myocardial fibrosis and reducing heart failure.