Laboratory of Cardiovascular Bioactive Molecule, School of Basic Medical Sciences, Peking University, Beijing, China.
J Card Fail. 2010 Jul;16(7):609-17. doi: 10.1016/j.cardfail.2010.02.002. Epub 2010 Mar 19.
Apelin is a cardiovascular peptide with multiple functions regulating homeostasis of the circulatory system and is the endogenous ligand of angiotensin II receptor like-1 (AGTRL1). Apelin has anti-inflammatory and inhibitory effects on release of inflammatory mediators. We aimed to analyze whether apelin antagonizes myocardial impairment in sepsis by attenuating inflammatory responses.
Male rats underwent sepsis by cecal ligation and puncture (CLP) after receiving low- or high-dose apelin for 3 days. Twenty hours later, rats with sepsis showed severe disturbance of hemodynamic features. Reverse transcription-polymerase chain reaction revealed decreased mRNA levels of apelin and AGTRL1 in myocardia of rats with sepsis. Enzyme immune assay detected a lower level of apelin in plasma and myocardia. Western blot analysis revealed decreased level of myocardial AGTRL1 protein. Low- and high-dose apelin administration ameliorated disorders of cardiac function: increased mean arterial blood pressure, attenuated heart rate, elevated +LVdp/dt(max) and LVdp/dt(max), and lowered left ventricular end-diastolic pressure. Rats treated with low- or high-dose apelin showed lower content of plasma monocyte chemoattractant protein 1 and interleukin 8. In cultured rat peritoneal macrophages, apelin directly inhibited the production of monocyte chemoattractant protein 1 and interleukin-8 induced by lipopolysaccharide.
These results suggest that apelin antagonizes cardiac impairment in sepsis by attenuating inflammatory responses and might be a promising therapeutic target for severe sepsis and septic shock.
Apelin 是一种心血管肽，具有调节循环系统内稳态的多种功能，是血管紧张素 II 受体样 1（AGTRL1）的内源性配体。Apelin 对炎症介质的释放具有抗炎和抑制作用。我们旨在分析 Apelin 是否通过减轻炎症反应来拮抗脓毒症引起的心肌损伤。
雄性大鼠在接受低剂量或高剂量 Apelin 治疗 3 天后通过盲肠结扎和穿孔（CLP）引发脓毒症。20 小时后，脓毒症大鼠表现出严重的血流动力学特征紊乱。逆转录-聚合酶链反应显示脓毒症大鼠心肌中 Apelin 和 AGTRL1 的 mRNA 水平降低。酶免疫测定法检测到血浆和心肌中 Apelin 的水平降低。Western blot 分析显示心肌 AGTRL1 蛋白水平降低。低剂量和高剂量 Apelin 给药改善了心脏功能障碍：平均动脉血压升高，心率减慢，+LVdp/dt(max) 和 LVdp/dt(max) 升高，左心室舒张末期压降低。给予低剂量或高剂量 Apelin 的大鼠显示出较低的血浆单核细胞趋化蛋白 1 和白细胞介素 8 含量。在培养的大鼠腹膜巨噬细胞中，Apelin 直接抑制了脂多糖诱导的单核细胞趋化蛋白 1 和白细胞介素 8 的产生。
这些结果表明，Apelin 通过减轻炎症反应拮抗脓毒症引起的心肌损伤，可能是严重脓毒症和脓毒性休克的有前途的治疗靶点。
