Liu Wenyuan, Han Qinghua, Liu Qinghua, Liang Gang, Wang Jin, Liu Chengfang
Department of Cardiology, The First Hospital of Shanxi Medical University, Taiyuan, Shanxi 030001, P.R. China.
Teaching and Research Department of Pathophysiology, Shanxi Medical University, Taiyuan, Shanxi 030001, P.R. China.
Mol Med Rep. 2015 Nov;12(5):6626-34. doi: 10.3892/mmr.2015.4244. Epub 2015 Aug 25.
The present study aimed to investigate the role and mode of action of urotensin II (U II) in the occurrence and progression of cardiac fibrosis in a pressure‑overload rat model. Coarctation of the abdominal aorta was used to establish an animal model, and postoperative echocardiography, hemodynamic detection, hematoxylin and eosin staining, Masson staining and immunohistochemistry were performed to assess the changes in cardiac function and pathology. The expression levels of U II, G‑protein‑coupled receptor 14 and collagen (Col) I and Col III in the myocardial tissues were also analyzed. Neonatal rat fibroblasts were isolated, cultured and subsequently, generations 3‑5 were randomly divided into different groups for the detection of Col I and Col III levels by enzyme‑linked immunosorbent assay and western blotting. The protein expression levels were markedly increased in the model group, and this increase correlated with an increase in myocardial fibrosis. In cultured neonatal rat fibroblast cells, 10‑8 mol/l U II significantly stimulated the synthesis of Col I and Col III (P<0.01) compared with the control group. Compared with the U II group, the administration of KT5720 (1 mol/l) or SB‑611812 (1 mol/l) significantly reduced the synthesis and expression levels of Col I and Col III (P<0.05). U II may exert an important role in the process of myocardial fibrosis in chronic pressure‑overload rats, and the cyclic adenosine monophosphate‑protein kinase A signaling pathway may be partly involved in this process.
本研究旨在探讨尾加压素 II（U II）在压力超负荷大鼠模型心脏纤维化发生发展中的作用及作用方式。采用腹主动脉缩窄法建立动物模型，并进行术后超声心动图、血流动力学检测、苏木精 - 伊红染色、Masson 染色和免疫组织化学，以评估心脏功能和病理学变化。还分析了心肌组织中 U II、G 蛋白偶联受体 14 以及 I 型胶原（Col）和 III 型胶原的表达水平。分离培养新生大鼠成纤维细胞，随后将第 3 - 5 代随机分为不同组，通过酶联免疫吸附测定和蛋白质印迹法检测 Col I 和 Col III 水平。模型组蛋白表达水平显著升高，且这种升高与心肌纤维化增加相关。在培养的新生大鼠成纤维细胞中，与对照组相比，10⁻⁸ mol/l 的 U II 显著刺激 Col I 和 Col III 的合成（P < 0.01）。与 U II 组相比，给予 KT5720（1 μmol/l）或 SB - 611812（1 μmol/l）可显著降低 Col I 和 Col III 的合成及表达水平（P < 0.05）。U II 可能在慢性压力超负荷大鼠心肌纤维化过程中发挥重要作用，环磷酸腺苷 - 蛋白激酶 A 信号通路可能部分参与此过程。
