Zhang Jing, Qi Yong-Fen, Geng Bin, Pan Chun-Shui, Zhao Jing, Chen Li, Yang Jun, Chang Jaw-Kang, Tang Chao-Shu
Institute of Cardiovascular Research, Peking University First Hospital, Beijing 100034, China.
Peptides. 2005 Sep;26(9):1632-9. doi: 10.1016/j.peptides.2005.02.008.
The omnipresent 6-kDa polypeptide relaxin (RLX) is emerging as a multifunctional endocrine and paracrine factor in a broad range of target tissues including cardiovascular tissues. To explore the pathophysiological roles of RLX in ischemic cardiovascular diseases, we studied the changes in RLX mRNA level in the myocardium and the effect of RLX supplements in rats with isoproterenol (ISO)-induced myocardial injury. In ISO-treated rats, RLX levels in myocardia and plasma increased 3.7- and 6.9-fold, respectively (P<0.01), the mRNA level increased significantly in myocardia compared with controls. Co-administration of RLX (0.2 and 2.0 microg/kg/d) and ISO increased left-ventricular pressure development and decreased left ventricular end-diastolic pressure (LVDEP) (all P<0.01). Malondialdehyde content in myocardia and lactate dehydrogenase and creatine phosphokinase activities in plasma in RLX-treated rats decreased markedly compared with that in ISO-treated alone rats (P<0.01 or P<0.05). In the high-dose RLX group, fibroblastic hyperplasia was relieved in myocardia, hydroxyproline level was lower, by 33% (P<0.05), and endothelin content in plasma was lower, by 31% (P<0.01) than in the ISO-alone group. Compared with control group, any indexes in sham rats treated with high-dose RLX were unaltered (all P>0.05). These results showed an up-regulation of myocardial RLX during ISO-induced myocardial ischemia injury and the protective effect of RLX on ISO-induced cardiac inhibition and fibrosis, which suggests that RLX could be an endogenous cardioprotective factor in ischemic heart diseases.
无处不在的6 kDa多肽松弛素（RLX）正在成为一种多功能内分泌和旁分泌因子，作用于包括心血管组织在内的广泛靶组织。为了探究RLX在缺血性心血管疾病中的病理生理作用，我们研究了心肌中RLX mRNA水平的变化以及RLX补充剂对异丙肾上腺素（ISO）诱导的心肌损伤大鼠的影响。在ISO处理的大鼠中，心肌和血浆中的RLX水平分别增加了3.7倍和6.9倍（P<0.01），与对照组相比，心肌中的mRNA水平显著增加。RLX（0.2和2.0μg/kg/d）与ISO联合给药可增加左心室压力发展并降低左心室舒张末期压力（LVDEP）（均P<0.01）。与单独接受ISO处理的大鼠相比，RLX处理的大鼠心肌中的丙二醛含量以及血浆中的乳酸脱氢酶和肌酸磷酸激酶活性显著降低（P<0.01或P<0.05）。在高剂量RLX组中，心肌中的成纤维细胞增生得到缓解，羟脯氨酸水平降低了33%（P<0.05），血浆中的内皮素含量比单独使用ISO组降低了31%（P<0.01）。与对照组相比，高剂量RLX处理的假手术大鼠的任何指标均未改变（均P>0.05）。这些结果表明，在ISO诱导的心肌缺血损伤期间心肌RLX上调，并且RLX对ISO诱导的心脏抑制和纤维化具有保护作用，这表明RLX可能是缺血性心脏病中的一种内源性心脏保护因子。
