Zhang Yong-Gang, Li Yu-Guang, Liu Bao-Guo, Wei Rui-Hong, Wang Dong-Ming, Tan Xue-Rui, Bu Ding-Fang, Pang Yong-Zheng, Tang Chao-Shu
Department of Cardiovascular Diseases, First Affiliated Hospital, Shantou University Medical College, Shantou 515041, China.
Acta Pharmacol Sin. 2007 Jan;28(1):36-43. doi: 10.1111/j.1745-7254.2007.00485.x.
To study whether urotensin II (UII), a potent vasoconstrictive peptide, is involved in the development of cardiac hypertrophy and fibrogenesis of rats induced by isoproterenol (ISO).
Thirty male Wistar rats were randomly divided into 3 groups. Group 1 was the healthy control group, group 2 was the ISO group, and group 3 was the ISO+UII group. In groups 2 and 3, ISO (5 mg x kg(-1) x d(-1)) was given (sc) once daily for 7 d. Group 3 was also given UII in the first day [3 nmol/kg (5 microg/kg), iv], followed by sc (1.5 microg/kg) twice daily. Group 1 received 0.9% saline. UII receptor (UT) mRNA expression was determined by RT-PCR. The contents of UII and angiotensin II (Ang II) were determined by radioimmunoassay. In vitro, the effects of UII on DNA/collagen synthesis of cardiac fibroblasts were determined by [3H]thymidine/[3H]proline incorporation.
The ratio of heart weight/body weight, plasma lactate dehydrogenase activity, myocardial malondialdehyde and hydroxyproline concentration increased significantly in the ISO group, as well as UT mRNA expression, plasma and cardiac UII and ventricular Ang II, compared with the control group (P< 0.01). ISO induced significant myocardial fibrogenesis. Moreover, UII+ISO co-treatment significantly increased the changes of biochemical markers of injury and the degree of cardiac hypertrophy and fibrosis. In vitro, 5 x 10(-9 )-5 x 10(-7 ) mol/L UII stimulated [3H]thymidine/[3H] proline incorporation into cardiac fibroblasts in a dose-dependent manner (P< 0.01).
These results suggest that UII was involved in the development of cardiac fibrosis and hypertrophy by synergistic effects with ISO.
研究强血管收缩肽尾加压素II（UII）是否参与异丙肾上腺素（ISO）诱导的大鼠心肌肥厚和纤维化的发生发展过程。
30只雄性Wistar大鼠随机分为3组。第1组为健康对照组，第2组为ISO组，第3组为ISO + UII组。第2组和第3组大鼠皮下注射ISO（5 mg·kg⁻¹·d⁻¹），每日1次，连续7天。第3组大鼠在第1天静脉注射UII [3 nmol/kg（5 μg/kg）]，随后每日皮下注射（1.5 μg/kg），每日2次。第1组大鼠注射0.9%生理盐水。采用逆转录-聚合酶链反应（RT-PCR）检测UII受体（UT）mRNA表达。采用放射免疫分析法测定UII和血管紧张素II（Ang II）含量。体外实验中，通过[³H]胸腺嘧啶核苷/[³H]脯氨酸掺入法测定UII对心肌成纤维细胞DNA/胶原蛋白合成的影响。
与对照组相比，ISO组大鼠心脏重量/体重比值、血浆乳酸脱氢酶活性、心肌丙二醛和羟脯氨酸浓度显著升高，UT mRNA表达、血浆和心脏UII及心室Ang II水平也显著升高（P < 0.01）。ISO诱导显著的心肌纤维化。此外，UII + ISO联合处理显著增加了损伤生化标志物的变化以及心肌肥厚和纤维化程度。体外实验中，5×10⁻⁹ - 5×10⁻⁷ mol/L UII以剂量依赖性方式刺激[³H]胸腺嘧啶核苷/[³H]脯氨酸掺入心肌成纤维细胞（P < 0.01）。
这些结果表明，UII通过与ISO协同作用参与心肌纤维化和肥厚的发生发展。
