脂蛋白a在心肌梗死模型大鼠中的作用及可能机制

Role of lipoprotein a in myocardial infarction model rats and its possible mechanism

目的:研究脂蛋白a[Lp(a)]在心肌梗死模型大鼠中的作用及可能机制。方法:选择30只SPF级SD健康大鼠,建立心肌梗死模型成功后分为模型组、过表达组、沉默组各10只。进行细胞转染建立稳定转染的Lp(a)蛋白过表达组、Lp(a)蛋白沉默组。检测3组大鼠心肌损伤情况、心肌细胞凋亡及心肌组织中蛋白表达量,并作组间比较。结果:沉默组左心室功能(LVEF)、心肌细胞增殖率以及心肌组织中磷酸化磷脂酰肌醇激酶(p-PI3K)、磷酸化蛋白激酶B(p-AKt)、磷酸化哺乳动物雷帕霉素靶蛋白(p-mTOR)、B淋巴细胞瘤-2(Bcl-2)蛋白表达量均高于过表达组,且左心室舒张期内径(LVIDd)、左心室收缩期内径(LVIDs)、心肌细胞凋亡率、迁移数、侵袭数以及Bax、Caspase-3、RhoA、ROCK1、ROCK2、肌球蛋白轻链(MLC)蛋白量均低于过表达组,具有统计学差异(P<0.05)。结论:沉默Lp(a)蛋白能够促进心肌梗死大鼠心肌细胞的增殖,抑制凋亡、迁移、侵袭,其作用机制可能与调控PI3K/AKt/mTOR、RhoA/ROCK信号通路有关。

Objective: To study the effect and possible mechanism of lipoprotein(Lp) a in myocardial infarction model rats. Methods: Thirty SPF SD rats were divided into model group, overexpression group and silence group with 10 rats in each group. The stable Lp(a) protein overexpression group and Lp(a)protein silencing group were established. Myocardial injury, cardiomyocyte apoptosis and protein expression were detected and compared among the three groups. Results: The left ventricular function(LVEF), cardiomyocyte proliferation rate and protein expression of phosphorylated phosphatidylinositol kinase(p-PI3 K), phosphorylated protein kinase B(p-Akt), phosphorylated mammalian target of rapamycin(p-mTOR) and B-cell lymphoma-2(Bcl-2) in the silenced group were higher than those in the overexpression group, and there was no significant difference between the two groups in left ventricular diastolic diameter(LVIDd), left ventricular systolic diameter(LVIDs), cardiomyocyte apoptosis rate, migration number, invasion number, Bax, caspase-3, RAS homologous gene family member a(RhoA), RhoA/Rho related coil forming protein kinase 1 and 2(ROCK1, ROCK2), myosin light chain(MLC). The protein content was lower than that of overexpression group. The difference was statistically significant(P<0. 05). Conclusion: Silencing Lp(a) protein can promote myocardial cell proliferation and inhibit apoptosis, migration and invasion in rats with myocardial infarction. Its mechanism may be related to the regulation of PI3 K/AKt/mTOR and RhoA/ROCK signaling pathway.