Kafkas University, Faculty of Medicine, Department of Pharmacology, Kars, Turkey.
Ataturk University, Faculty of Medicine, Department of Pharmacology, Erzurum, Turkey.
Life Sci. 2019 Mar 15;221:327-334. doi: 10.1016/j.lfs.2019.02.039. Epub 2019 Feb 20.
Sepsis is a complex pathophysiological event involving systemic inflammatory response syndrome, multiple organ dysfunction syndrome and tissue damage such as acute lung injury (ALI). Although many new mechanisms are being investigated to enlighten the pathophysiology of sepsis, there is no effective treatment protocol yet. Antioxidant, antibacterial and antiinflammatory effects of gossypin (GOS)-like flavonoids have been shown and we have hypothesized that GOS have roles in sepsis induced inflammation of lungs.
Cecal ligation and puncture (CLP) induced sepsis model was induced in rats. Effects of GOS on oxidative stress, histopathology, nuclear factor kappa B (NF-κB), IL-6 positivity and NLRP3, HMGβ1, TNF-α, NF-κB, IL-1β mRNA expression levels were evaluated in lung tissues of the septic rats.
GOS 20 (20 mg/kg) administration to septic rats decreased oxidative stress and supported antioxidant system in lungs. GOS administration also decreased the tissue NF-κB and IL-6 immunopositivity, which is high in septic rats; and decreased the sepsis-induced lung injury. HMGβ1, NLRP3, NF-κB, IL-1β, and TNF-α mRNA expression significantly increased in the CLP group. Both doses of GOS significantly reduced these mRNA expression as compared with the levels in the CLP group demonstrating its anti-inflammatory potential.
GOS administration, may represent a novel treatment for the prevention of lung damage occurred after sepsis induction. This effect of GOS might be related to its anti-inflammatory potential that result in decreased cytokine response and improved oxidative status.
败血症是一种涉及全身炎症反应综合征、多器官功能障碍综合征和组织损伤（如急性肺损伤）的复杂病理生理事件。尽管许多新的机制正在被研究以阐明败血症的病理生理学，但目前还没有有效的治疗方案。棉花素（GOS）样类黄酮具有抗氧化、抗菌和抗炎作用，我们假设 GOS 在败血症引起的肺部炎症中发挥作用。
在大鼠中诱导盲肠结扎和穿刺（CLP）诱导的败血症模型。评估 GOS 对败血症大鼠肺部氧化应激、组织病理学、核因子 kappa B（NF-κB）、IL-6 阳性和 NLRP3、HMGβ1、TNF-α、NF-κB、IL-1β mRNA 表达水平的影响。
GOS 20（20mg/kg）给药可降低败血症大鼠肺部的氧化应激并支持抗氧化系统。GOS 给药还降低了组织中 NF-κB 和 IL-6 的免疫阳性率，而败血症大鼠的 NF-κB 和 IL-6 免疫阳性率较高；并减轻了败血症引起的肺损伤。CLP 组中 HMGβ1、NLRP3、NF-κB、IL-1β 和 TNF-α mRNA 表达显著增加。与 CLP 组相比，两种剂量的 GOS 均显著降低了这些 mRNA 的表达，表明其具有抗炎潜力。
GOS 的给药可能代表了一种预防败血症诱导后发生肺损伤的新治疗方法。GOS 的这种作用可能与其抗炎潜力有关，从而降低细胞因子反应并改善氧化状态。
