二甲双胍通过 AMPK 通路减轻 2 型糖尿病受体大鼠肺缺血再灌注损伤和坏死性凋亡。
Metformin attenuates lung ischemia-reperfusion injury and necroptosis through AMPK pathway in type 2 diabetic recipient rats.
机构信息
Department of Anesthesiology, Hei Long Jiang Province Key Laboratory of Research on Anesthesiology and Critical Care Medicine, Second Affiliated Hospital of Harbin Medical University, NO.246, Xuefu Road, Nangang District, Harbin, Heilongjiang Province, 150081, China.
Department of Anesthesiology, Sixth Affiliated Hospital of Harbin Medical University, Harbin, China.
出版信息
BMC Pulm Med. 2024 May 14;24(1):237. doi: 10.1186/s12890-024-03056-z.
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.
背景
糖尿病（DM）可加重肺缺血再灌注（I/R）损伤，是肺移植受体死亡的重要危险因素。二甲双胍可保护多种器官免受 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 I/R 损伤的作用及机制。
方法
将 Sprague-Dawley 大鼠随机分为以下六组：对照组+假手术组（CS 组）、对照组+I/R 组（CIR 组）、糖尿病组+假手术组（DS 组）、糖尿病组+I/R 组（DIR 组）、糖尿病组+I/R+二甲双胍组（DIRM 组）和糖尿病组+I/R+二甲双胍+Compound C 组（DIRMC 组）。对照组和糖尿病大鼠行假手术或左肺移植术。再灌注 24 h 后测定肺功能、肺泡毛细血管通透性、炎症反应、氧化应激、坏死性凋亡及 p-AMPK/AMPK 比值。
结果
与 CIR 组相比，DIR 组肺功能下降，肺泡毛细血管通透性增加，炎症反应、氧化应激和坏死性凋亡增加，p-AMPK/AMPK 比值降低；二甲双胍改善了肺移植物的功能，降低了肺泡毛细血管通透性、炎症反应、氧化应激和坏死性凋亡，并增加了 p-AMPK/AMPK 比值；而 Compound C 则削弱了二甲双胍的保护作用。
结论
二甲双胍通过 AMPK 通路减轻 2 型糖尿病肺移植受体大鼠的肺 I/R 损伤和坏死性凋亡。
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