Effects of Aliskiren, an RAAS inhibitor, on a carrageenan-induced pleurisy model of rats

Abstract Our aim is to investigate the potentially preventive effects of Aliskiren in a carrageenan-induced lung pleurisy model and to compare the standard anti-inflammatory agents, indomethacin and dexamethasone. The pleurisy model was induced through the injection of carrageenan (0.2 ml-%2) into the pleural cavity. After the experiment, serum and lung tissues were collected and biochemical, molecular and pathological examinations were performed. In our study, pleural inflammation decreased superoxide dismutase activity and the glutathione level and increased the malondialdehyde level in the lung of rats, while Aliskiren increased the superoxide dismutase activity and glutathione level and decreased the malondialdehyde level. In addition, carrageenan-induced pleurisy caused a significant increase in pro-inflammatory cytokines mRNA expressions (TNF-α, IL-1β, and NF-KB), while Aliskiren administration decreased their expressions as well as the standard treatments, indomethacin and dexamethasone, did. Aliskiren administration at the 200 mg/kg dose protected the lungs in the pathological evaluation, especially against inflammatory cell infiltration and edematous lesions. It appears that Aliskiren protects the lung from carrageenan-induced pleurisy damage by regulating inflammation and antioxidant-oxidant balance via Renin Angiotensin Aldosterone System inhibition.

摘要 本研究旨在探究阿利吉仑（Aliskiren）在角叉菜胶（carrageenan）诱导的肺胸膜炎模型中的潜在预防作用，并与标准抗炎药物吲哚美辛（indomethacin）、地塞米松（dexamethasone）进行对比。本模型通过向大鼠胸膜腔内注射0.2 mL体积分数为2%的角叉菜胶构建。实验结束后，采集大鼠血清与肺组织样本，开展生化、分子生物学及病理学检测。本研究发现，角叉菜胶诱导的胸膜炎症会降低大鼠肺组织中超氧化物歧化酶（superoxide dismutase）活性与谷胱甘肽（glutathione）水平，同时升高丙二醛（malondialdehyde）含量；而阿利吉仑可提升上述酶活性与谷胱甘肽水平，并降低丙二醛含量。此外，角叉菜胶诱导的胸膜炎可显著上调促炎细胞因子（pro-inflammatory cytokines）的mRNA表达水平，包括肿瘤坏死因子-α（TNF-α）、白细胞介素-1β（IL-1β）及核因子κB（NF-κB）；阿利吉仑给药可下调这些细胞因子的表达，其效果与吲哚美辛、地塞米松这两种标准抗炎治疗药物一致。以200 mg/kg剂量给予阿利吉仑时，病理学评估显示其可保护肺组织，尤其可抑制炎性细胞浸润与水肿性损伤。综上，阿利吉仑可通过抑制肾素-血管紧张素-醛固酮系统（Renin Angiotensin Aldosterone System, RAAS），调节炎症反应与抗氧化-氧化平衡，从而减轻角叉菜胶诱导的肺胸膜炎损伤。