阿霉素诱导大鼠急性心肌损伤模型中整合素β3与内质网应激及Bcl2/Bax基因的相关性研究

Correlation of Integrinβ3 with Endoplasmic Reticulum Stress and Bcl2/Bax Gene in Adriamycin-induced Acute Myocardial Injury Model in Rats

目的探究阿霉素诱导大鼠急性心肌损伤模型中整合素β3与内质网应激(ERS)及Bcl2/Bax基因的相关性。方法通过一次性注射大量阿霉素诱导急性心肌损伤,选择25只作为模型组;另选择25只作为健康组。检测各组大鼠心肌损伤及心功能情况:射血分数(EF)、左室舒张末期内径(LVEDD)、左室收缩末期内径(LVESD)。检测心肌组织中整合素β3、ERS标志(GRP78、PERK)和凋亡(Bcl2、Bax)标志基因mRNA和蛋白的水平。阿霉素诱导的急性心肌损伤模型大鼠心肌组织中整合素βmRNA或蛋白与GRP78、PERK、Bax、Bcl2蛋白的相关性利用Pearson检验进行评估。结果与健康组比较,阿霉素诱导的模型组大鼠的EF(46.08±4.25)%显著降低(P<0.05),而LVEDD(7.83±0.79)mm和LVESD(5.65±0.64)mm显著升高(P<0.05)。模型组心肌组织中整合素β3、GRP78、PERK、Bax mRNA表达量显著高于健康组(P<0.05),而Bcl2 mRNA蛋白表达量显著低于健康组(P<0.05)。整合素mRNA和蛋白的表达量与ERS标志蛋白的表达量均正相关(P<0.05),与促凋亡蛋白Bax蛋白表达量正相关(P<0.05),与抗凋亡蛋白Bcl2蛋白表达量负相关(P<0.05)。结论阿霉素诱导的急性心肌损伤的大鼠心肌组织中整合素β3过表达,并且ERS和促凋亡蛋白水平升高,整合素β3与其正相关;抗凋亡蛋白水平降低,整合素β3与其负相关。

Objective To explore the correlation between integrinβ3 and endoplasmic reticulum stress(ERS)and Bcl2/Bax genes in the acute myocardial injury model induced by adriamycin in rats.Method Acute myocardial injury was induced by a one-time injection of a large amount of doxorubicin,and 25 mice were selected as the model group.Twenty-five healthy rats were selected as the healthy group.Myocardial damage and cardiac function in each group:ejection fraction(EF),left ventricular end-diastolic diameter(LVEDD)and left ventricular end-systolic diameter(LVESD)were detected.The levels of mRNA and protein of integrinβ3,ERS markers(GRP78,PERK),and apoptosis marker(Bcl2,Bax)in myocardial tissue were detected.The Pearson evaluated the correlation between integrinβmRNA or protein and GRP78,PERK,Bax,and Bcl2 protein in the myocardial tissue of rats with acute myocardial injury induced by doxorubicin.Results Compared with the healthy group,the EF(46.08±4.25)%of the adriamycin-induced model group was significantly reduced(P<0.05),while the LVEDD(7.83±0.79)mm and LVESD(5.65±0.64)mm were significantly increased(P<0.05).The expression of integrinβ3,GRP78,PERK,and Bax mRNA in the myocardial tissue of the model group was significantly higher than those of the healthy group(P<0.05),while the expression of Bcl2 mRNA protein were significantly lower than those of the healthy group(P<0.05).The expression of integrin mRNA and protein is positively correlated with the expression of ERS marker protein(P<0.05),and is positively correlated with the expression of proapoptotic protein Bax(P<0.05),and is negatively correlated with the expression of anti-apoptotic protein Bcl2(P<0.05).Conclusion Integrinβ3 is overexpressed in the myocardial tissue of rats with acute myocardial injury induced by adriamycin.The levels of ERS and pro-apoptotic proteins are increased,and integrinβ3 is positively correlated with it;anti-apoptotic protein levels are reduced,and integrinβ3 is negatively Related.