PDF(Pubmed)
Abstract：
BACKGROUND: Diabetes mellitus (DM) can aggravate lung ischemia-reperfusion (I/R) injury and is a significant risk factor for recipient mortality after lung transplantation. Metformin protects against I/R injury in a variety of organs. However, the effect of metformin on diabetic lung I/R injury remains unclear. Therefore, this study aimed to observe the effect and mechanism of metformin on lung I/R injury following lung transplantation in type 2 diabetic rats.
METHODS: Sprague-Dawley rats were randomly divided into the following six groups: the control + sham group (CS group), the control + I/R group (CIR group), the DM + sham group (DS group), the DM + I/R group (DIR group), the DM + I/R + metformin group (DIRM group) and the DM + I/R + metformin + Compound C group (DIRMC group). Control and diabetic rats underwent the sham operation or left lung transplantation operation. Lung function, alveolar capillary permeability, inflammatory response, oxidative stress, necroptosis and the p-AMPK/AMPK ratio were determined after 24 h of reperfusion.
RESULTS: Compared with the CIR group, the DIR group exhibited decreased lung function, increased alveolar capillary permeability, inflammatory responses, oxidative stress and necroptosis, but decreased the p-AMPK/AMPK ratio. Metformin improved the function of lung grafts, decreased alveolar capillary permeability, inflammatory responses, oxidative stress and necroptosis, and increased the p-AMPK/AMPK ratio. In contrast, the protective effects of metformin were abrogated by Compound C.
CONCLUSIONS: Metformin attenuates lung I/R injury and necroptosis through AMPK pathway in type 2 diabetic lung transplant recipient rats.
METHODS: Sprague-Dawley rats were randomly divided into the following six groups: the control + sham group (CS group), the control + I/R group (CIR group), the DM + sham group (DS group), the DM + I/R group (DIR group), the DM + I/R + metformin group (DIRM group) and the DM + I/R + metformin + Compound C group (DIRMC group). Control and diabetic rats underwent the sham operation or left lung transplantation operation. Lung function, alveolar capillary permeability, inflammatory response, oxidative stress, necroptosis and the p-AMPK/AMPK ratio were determined after 24 h of reperfusion.
RESULTS: Compared with the CIR group, the DIR group exhibited decreased lung function, increased alveolar capillary permeability, inflammatory responses, oxidative stress and necroptosis, but decreased the p-AMPK/AMPK ratio. Metformin improved the function of lung grafts, decreased alveolar capillary permeability, inflammatory responses, oxidative stress and necroptosis, and increased the p-AMPK/AMPK ratio. In contrast, the protective effects of metformin were abrogated by Compound C.
CONCLUSIONS: Metformin attenuates lung I/R injury and necroptosis through AMPK pathway in type 2 diabetic lung transplant recipient rats.
摘要：
背景：糖尿病（DM）可加重肺缺血再灌注（I/R）损伤，是肺移植后受体死亡的重要危险因素。二甲双胍可防止多种器官的I/R损伤。然而,二甲双胍对糖尿病肺I/R损伤的影响尚不清楚.因此,本研究旨在观察二甲双胍对2型糖尿病大鼠肺移植后肺缺血再灌注损伤的影响及机制。
方法:SD大鼠随机分为6组:对照组+假手术组(CS组),控制+I/R组(CIR组)，DM+假手术组（DS组），DM+I/R组(DIR组)，DM+I/R+二甲双胍组(DIRM组)和DM+I/R+二甲双胍+化合物C组(DIRMC组)。对照组和糖尿病大鼠进行了假手术或左肺移植手术。肺功能,肺泡毛细血管通透性，炎症反应，氧化应激，再灌注24小时后测定细胞凋亡和p-AMPK/AMPK比值。
结果：与CIR组相比，DIR组表现为肺功能下降，肺泡毛细血管通透性增加，炎症反应，氧化应激和坏死，但降低了p-AMPK/AMPK比值。二甲双胍改善移植肺功能,肺泡毛细血管通透性降低，炎症反应，氧化应激和坏死，并增加p-AMPK/AMPK比值。相比之下,复方C消除二甲双胍的保护作用。
结论：二甲双胍通过AMPK途径减轻2型糖尿病肺移植受体大鼠的I/R损伤和坏死。
方法:SD大鼠随机分为6组:对照组+假手术组(CS组),控制+I/R组(CIR组)，DM+假手术组（DS组），DM+I/R组(DIR组)，DM+I/R+二甲双胍组(DIRM组)和DM+I/R+二甲双胍+化合物C组(DIRMC组)。对照组和糖尿病大鼠进行了假手术或左肺移植手术。肺功能,肺泡毛细血管通透性，炎症反应，氧化应激，再灌注24小时后测定细胞凋亡和p-AMPK/AMPK比值。
结果：与CIR组相比，DIR组表现为肺功能下降，肺泡毛细血管通透性增加，炎症反应，氧化应激和坏死，但降低了p-AMPK/AMPK比值。二甲双胍改善移植肺功能,肺泡毛细血管通透性降低，炎症反应，氧化应激和坏死，并增加p-AMPK/AMPK比值。相比之下,复方C消除二甲双胍的保护作用。
结论：二甲双胍通过AMPK途径减轻2型糖尿病肺移植受体大鼠的I/R损伤和坏死。
