八肽胆囊收缩素可减少心肌梗死后大鼠的心肌纤维化，改善心脏重构。
Cholecystokinin octapeptide reduces myocardial fibrosis and improves cardiac remodeling in post myocardial infarction rats.
机构信息
Laboratory of Cardiovascular Internal Medicine Department, The First Affiliated Hospital of Harbin Medical University, Harbin, China.
Laboratory of Cardiovascular Internal Medicine Department, The First Affiliated Hospital of Harbin Medical University, Harbin, China.
出版信息
Int J Biochem Cell Biol. 2020 Aug;125:105793. doi: 10.1016/j.biocel.2020.105793. Epub 2020 Jun 15.
BACKGROUND/AIMS: Myocardial infarction (MI) increases myocardial fibrosis (MF) and subsequent cardiac remodeling. Cholecystokinin octapeptide (CCK-8) is expressed in cardiomyocytes and plays an important role in cardiovascular regulation. In this study, we intend to use a rat model of myocardial infarction to evaluate the effects of CCK-8 on myocardial fibrosis and cardiac remodeling.
METHODS
Male Sprague-Dawley rats were separated into 3 groups: sham operation, MI + NaCl, and MI + CCK-8. All rats were subjected to left coronary artery ligation to induce MI or sham operation and then treated with CCK-8 or saline for 28 days. After 4 weeks, echocardiography was performed to assess cardiac function and myocardial fibrosis was evaluated using H&E and Masson's Trichrome-stained sections. The levels of BNP, CCK-8 in the plasma of all rats were detected by ELISA; RNA sequencing (RNA-seq) analysis was also adapted to detect differentially expressed genes in myocardial tissues of each group. Myocardial expression of fibrosis markers was analyzed by western blotting, immunohistochemistry and qRT-PCR.
RESULTS
CCK-8 was demonstrated to improve left ventricular function and results of H&E staining, Masson's trichrome staining, immunohistochemistry and western blotting showed that CCK-8 attenuated MF. Gene expression profiles of the left ventricles were analysed by RNA-seq and validated by qRT-PCR. Cardiac fibrosis genes were downregulated by CCK-8 in the left ventricle.
SIGNIFICANCE
CCK-8 can alleviate fibrosis in the noninfarcted regions and delay the left ventricular remodeling and the progress of heart failure in a MI rat model.
背景/目的：心肌梗死（MI）会增加心肌纤维化（MF），进而导致心脏重构。胆囊收缩素八肽（CCK-8）在心肌细胞中表达，在心脑血管调节中发挥重要作用。在本研究中，我们拟采用心肌梗死大鼠模型，评估 CCK-8 对心肌纤维化和心脏重构的影响。
方法
雄性 Sprague-Dawley 大鼠分为 3 组：假手术组、MI+NaCl 组和 MI+CCK-8 组。所有大鼠均进行左冠状动脉结扎以诱导 MI 或假手术，然后用 CCK-8 或生理盐水处理 28 天。4 周后，行超声心动图检查以评估心功能，采用 H&E 和 Masson 三色染色切片评估心肌纤维化。通过 ELISA 检测所有大鼠血浆中 BNP、CCK-8 的水平；还采用 RNA 测序（RNA-seq）分析检测各组心肌组织中差异表达的基因。通过 Western 印迹、免疫组化和 qRT-PCR 分析心肌纤维化标志物的表达。
结果
CCK-8 可改善左心室功能，H&E 染色、Masson 三色染色、免疫组化和 Western 印迹结果表明 CCK-8 可减轻 MF。通过 RNA-seq 分析左心室的基因表达谱，并通过 qRT-PCR 进行验证。CCK-8 可下调左心室的心脏纤维化基因。
意义
CCK-8 可减轻非梗死区的纤维化，并延缓 MI 大鼠模型左心室重构和心力衰竭的进展。
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