促红细胞生成素衍生物螺旋B表面肽对表柔比星诱发大鼠心肌损伤的改善作用及机制研究
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篇名: 促红细胞生成素衍生物螺旋B表面肽对表柔比星诱发大鼠心肌损伤的改善作用及机制研究
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摘要: 目的:研究促红细胞生成素衍生物螺旋B表面肽(HBSP)对表柔比星诱发大鼠心肌损伤的改善作用及机制。方法:将SD大鼠随机分为对照组、模型组、促红细胞生成素(EPO)组和HBSP组,每组10只。除对照组外,其余各组大鼠均腹腔注射表柔比星2.5 mg/kg,每周1次,连续6周复制心肌损伤模型,EPO组和HBSP组大鼠分别腹腔注射重组人促红细胞生成素(rhEPO)5 000 u/kg或HBSP 60 μg/kg,每周3次(分别于表柔比星给药前1天、给药后第1天以及给药后第3天给药),连续6周。以首次给药开始计时,第11周称各组大鼠体质量,超声心动图检测其心功能[左室舒张末期内径(LVIDd)、射血分数(EF)、缩短分数(FS)及心输出量(CO)],酶联免疫吸附法测定其血清中肌钙蛋白I(cTnI)、氨基末端B型利钠肽原(NT-proBNP)的含量,逆转录-聚合酶链式反应检测其心肌组织中磷脂酰肌醇-3-激酶(PI3K)和蛋白激酶B(Akt)mRNA的表达,Western blot法检测其心肌组织中p-PI3K和p-Akt蛋白的表达。结果:在研究期内,模型组有2只大鼠死亡,EPO组有1只大鼠死亡,HBSP组无大鼠死亡。与对照组比较,模型组大鼠体质量、EF、FS、CO均显著降低,LVIDd和cTnI、NT-proBNP含量均显著增加,PI3K、Akt mRNA表达水平及p-PI3K、p-Akt蛋白表达水平均显著降低,以上差异均有统计学意义(P<0.05)。与模型组比较,EPO组及HBSP组大鼠体质量、EF、FS、CO均显著增加,LVIDd和cTnI、NT-proBNP含量显著降低,PI3K、Akt mRNA表达水平及p-PI3K、p-Akt蛋白表达水平均显著升高,以上差异均有统计学意义(P<0.05)。与EPO组比较,HBSP组大鼠cTnI、NT-proBNP含量均显著降低,差异均有统计学意义(P<0.05)。结论:HBSP对大鼠心肌损伤具有与EPO相当的改善作用,且毒性更小,二者改善心肌损伤的作用机制可能与激活PI3K/Akt信号通路有关。
ABSTRACT: OBJECTIVE: To study the improvement effects and its mechanism of erythropoietin derivative helix B surface peptide (HBSP) on epirubicin-induced myocardial injury in rats. METHODS: SD rats were randomly divided into control group, model group, erythropoietin (EPO) group and HBSP group, with 10 rats in each group. Except for control group, other groups were given epirubicin 2.5 mg/kg intraperitoneally, once a week, for consecutive 6 weeks to induce myocardial injury model. EPO group and HBSP groups were given rhEPO 5 000 u/kg or HBSP 60 μg/kg intraperitoneally, 3 times a week (one day before medication, first day and third day after medication of epirubicin), for consecutive 6 weeks. At the beginning of the first administration, the rats were weighed at the 11th week. The cardiac function was measured by echocardiography [left ventricular end-diastolic diameter (LVIDd), ejection fraction (EF), fractional shortening (FS) and cardiac output(CO)]. The serum levels of troponin I (cTnI) and amino-terminal B-type natriuretic peptide (NT-proBNP) were determined by ELISA. mRNA expression of PI3K and Akt in myocardial tissue was detected by RT-PCR. The protein expression of p-PI3K and p-Akt in rat myocardium were detected by Western blot. RESULTS: During research period, two rats died in model group, one in EPO group and none in HBSP group. Compared with control group, body weight, the levels of EF, FS and CO were decreased significantly in model group, while the contents of LVIDd and cTnI, NT-proBNP were increased significantly; mRNA expression of PI3K and Akt as well as protein expression of p-PI3K and p-Akt were decreased significantly, above differences were statistical significant (P<0.05). Compared with model group, body weight, the levels of EF, FS and CO were increased significantly in EPO group and HBSP group, while the contents of LVIDd and cTnI, NT-proBNP were decreased significantly; mRNA expression of PI3K and Akt as well as protein expression of p-PI3K and p-Akt were increased significantly, above differences were statistical significant (P<0.05). Compared with EPO group, the contents of cTnI and NT-proBNP were decreased significantly in HBSP group, with statistical significance (P<0.05). CONCLUSIONS: HBSP can improve myocardial injury in rats as much as EPO, and has less toxity. Their mechanism may be related to the activation of PI3K/Akt signaling pathway.
期刊: 2019年第30卷第19期
作者: 于秀燕,李跃荣,徐会圃,赵冬冬,陈薇薇,郭纪伟,马宝新
AUTHORS: YU Xiuyan,LI Yuerong,XU Huipu,ZHAO Dongdong,CHEN Weiwei,GUO Jiwei,MA Baoxin
关键字: 螺旋B表面肽;表柔比星;心肌损伤;磷脂酰肌醇-3-激酶;蛋白激酶B;大鼠
KEYWORDS: Helix B surface peptide; Epirubicin; Myocardial injury; PI3K; Akt; Rat
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