Akpinar Erol, Halici Zekai, Cadirci Elif, Bayir Yasin, Karakus Emre, Calik Muhammet, Topcu Atilla, Polat Beyzagul
Department of Pharmacology, Ataturk University Faculty of Medicine, 25240, Erzurum, Turkey.
Naunyn Schmiedebergs Arch Pharmacol. 2014 Oct;387(10):969-78. doi: 10.1007/s00210-014-1014-0. Epub 2014 Jul 9.
Sepsis and sepsis-related acute lung injuries (ALIs) are one of the main causes of death among hospitalized patients. Renin-angiotensin-aldosterone system (RAAS) has been reported to have role in sepsis. However, there is no study on aliskiren, a renin inhibitor, on sepsis-induced ALI. We aimed to investigate the potential protective effects of aliskiren in a model of cecal ligation and puncture (CLP)-induced lung injury. The rats were separated into five groups: sham, CLP, CLP + aliskiren 50 mg/kg (per orem (p.o.)), CLP + aliskiren 100 mg/kg (p.o.), and sham + aliskiren 100 mg/kg (p.o.). CLP model was applied via ligation of cecum and two punctures. After experiment, biochemical, molecular, and pathologic examinations were performed on lung and serum samples of rats. In our study, sepsis decreased superoxide dismutase (SOD) and glutathione (GSH) and increased malondialdehyde (MDA) in lung tissues of rats while aliskiren increased the SOD and GSH and decreased MDA. Also, sepsis caused a significant increase in pro-inflammatory cytokine levels (TNF-α, IL-1β, and IL-6) while aliskiren administration decreased these cytokines. Also, aliskiren administration at high dose protected lungs in pathologic evaluation. As a result of RAAS inhibition, aliskiren caused a decrease in serum angiotensin II level and increase in serum renin level. In light of these observations, we can suggest that the therapeutic administration of aliskiren prevented oxidative stress changes and cytokine changes and also protected lung tissues during CLP-induced sepsis by changing status of RAAS.
脓毒症及脓毒症相关急性肺损伤（ALI）是住院患者主要死亡原因之一。据报道，肾素 - 血管紧张素 - 醛固酮系统（RAAS）在脓毒症中发挥作用。然而，尚无关于肾素抑制剂阿利吉仑对脓毒症诱导的ALI影响的研究。我们旨在研究阿利吉仑在盲肠结扎穿刺（CLP）诱导的肺损伤模型中的潜在保护作用。将大鼠分为五组：假手术组、CLP组、CLP + 阿利吉仑50 mg/kg（口服）组、CLP + 阿利吉仑100 mg/kg（口服）组和假手术 + 阿利吉仑100 mg/kg（口服）组。通过结扎盲肠并穿刺两次建立CLP模型。实验结束后，对大鼠的肺组织和血清样本进行生化、分子和病理检查。在我们的研究中，脓毒症使大鼠肺组织中的超氧化物歧化酶（SOD）和谷胱甘肽（GSH）减少，丙二醛（MDA）增加，而阿利吉仑使SOD和GSH增加，MDA减少。此外，脓毒症导致促炎细胞因子水平（TNF-α、IL-1β和IL-6）显著升高，而给予阿利吉仑可降低这些细胞因子水平。而且，高剂量阿利吉仑给药在病理评估中对肺有保护作用。由于RAAS受到抑制，阿利吉仑使血清血管紧张素II水平降低，血清肾素水平升高。鉴于这些观察结果，我们可以认为，阿利吉仑的治疗性给药可预防氧化应激变化和细胞因子变化，并且通过改变RAAS状态在CLP诱导的脓毒症期间保护肺组织。
