Hesperetin attenuates ventilator-induced acute lung injury through inhibition of NF-κB-mediated inflammation

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• 作者：Hongzhong Ma^a ; ^{hzhongma520@yeah.net" class="auth_mail" title="E-mail the corresponding author} ; Xiaoli Feng^b ; Suchun Ding^a
• 关键词：Hesperetin ; Ventilator-induced ALI ; PPAR-γ ; NF-κB pathway ; Inflammation
• 刊名：European Journal of Pharmacology
• 出版年：2015
• 出版时间：15 December 2015
• 年：2015
• 卷：769
• 期：Complete
• 页码：333-341
• 全文大小：4642 K

文摘

Hesperetin, a major bioflavonoid in sweet oranges and lemons, has been reported to have anti-inflammatory properties. However, the effect of hesperetin on ventilator-induced acute lung injury has not been studied. In present study, we investigated the protective effect of hesperetin on ventilator-induced acute lung injury in rats. Rats were orally administered hesperetin (10, 20, or 40 mg/kg) two hour before acute lung injury was induced by mechanical ventilation. Rats were then randomly divided into six groups: the lung protective ventilation group (n=20, LV group), injurious ventilation group (n=20, HV group), vehicle-treated injurious ventilation group (n=20, LV+vehicle group), hesperetin (10 mg/kg)-treated acute lung injury group (n=20, HV+Hsp (10 mg)), hesperetin (20 mg/kg)-treated acute lung injury group (n=20, HV+Hsp (20 mg)), and hesperetin (40 mg/kg)-treated acute lung injury group (n=20, HV+Hsp (40 mg)). The lung tissues and bronchoalveolar lavage fluid were isolated for subsequent measurements. Treatment with hesperetin dramatically improved the histology of lung tissue, and reduced the wet/dry ratio, myeloperoxidase activity, protein concentration, and production of tumor necrosis factor (TNF)-α, interleukin (IL)-6, IL-1β, and MIP-2 in the bronchoalveolar lavage fluid of rats with ventilator-induced acute lung injury. Additionally, our study indicated that this protective effect of hesperetin results from its ability to increase the expression of peroxisome proliferator-activated receptor (PPAR)-γ and inhibit the activation of the nuclear factor (NF)-κB pathway. These results suggest that hesperetin may be a potential novel therapeutic candidate for protection against ventilator-induced acute lung injury.