Department of Anesthesiology, The Heilongjiang Province Key Laboratory of Research on Anesthesiology and Critical Care Medicine, The Second Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang 150001, P.R. China.
Mol Med Rep. 2018 May;17(5):7191-7201. doi: 10.3892/mmr.2018.8748. Epub 2018 Mar 14.
Adiponectin (APN) has been associated with the pathogenesis of acute brain, liver and heart injury. However, the role of APN in lung ischemia-reperfusion injury (LIRI) in diabetes mellitus remains unclear. To investigate this, the present study evaluated the effects of APN on lung dysfunction and pathological alterations in rats with type 2 diabetes mellitus via lung ischemia/reperfusion (I/R). The lung‑protective effects of APN globular domain (gAPN) in rats with type 2 diabetes mellitus were also investigated by measuring the oxygenation index, inflammatory cytokines, lung edema, histopathology, oxidative stress, apoptosis and the protein expression levels of phosphorylated 5'adenosine monophosphate‑activated protein kinase (p‑AMPK), endothelial nitric oxide synthase (eNOS) and inducible nitric oxide synthase (iNOS). The results of the present study demonstrated that the diabetes mellitus rats + I/R (DIR) group exhibited greater concentrations of tumor necrosis factor‑α and interleukin‑6, and increases in the wet‑weight to dry‑weight ratio, lung injury score, oxidative stress and cellular apoptosis. These effects were accompanied by lower pulmonary oxygenation compared with the normal rat + I/R (NIR) group (P<0.05). Additionally, all of these alterations were attenuated in the NIR + gAPN and DIR + gAPN groups compared with in the NIR and DIR groups, respectively. In the DIR group, the expression levels of p‑AMPK/AMPK and eNOS were significantly downregulated, and the levels of iNOS were upregulated, compared with those of the NIR group. Treatment with APN activated AMPK, increased eNOS expression and attenuated iNOS expression. The results of the present study demonstrated that APN exerted protective effects against LIRI via its anti‑inflammatory, antioxidative stress and anti‑apoptotic activities. These protective effects of APN were eliminated in rats with type 2 diabetes mellitus, in which LIRI was exacerbated. The present study indicated that APN may be a potential therapeutic agent for LIRI in type 2 diabetes mellitus.
脂联素 (APN) 与急性脑、肝和心脏损伤的发病机制有关。然而，APN 在糖尿病合并肺缺血再灌注损伤 (LIRI) 中的作用尚不清楚。为了研究这一点，本研究通过肺缺血/再灌注 (I/R) 评估了 APN 对 2 型糖尿病大鼠肺功能障碍和病理改变的影响。还通过测量氧合指数、炎症细胞因子、肺水肿、组织病理学、氧化应激、细胞凋亡以及磷酸化 5'腺嘌呤单核苷酸激活蛋白激酶 (p-AMPK)、内皮型一氧化氮合酶 (eNOS) 和诱导型一氧化氮合酶 (iNOS) 的蛋白表达水平，研究了 APN 球状结构域 (gAPN) 在 2 型糖尿病大鼠中的肺保护作用。本研究结果表明，糖尿病大鼠+I/R (DIR) 组肿瘤坏死因子-α和白细胞介素-6 浓度较高，湿重/干重比、肺损伤评分、氧化应激和细胞凋亡增加。与正常大鼠+I/R (NIR) 组相比，这会导致肺氧合作用降低 (P<0.05)。此外，与 NIR 组和 DIR 组相比，NIR + gAPN 组和 DIR + gAPN 组的所有这些变化均减弱。与 NIR 组相比，DIR 组 p-AMPK/AMPK 和 eNOS 的表达水平明显下调，而 iNOS 的水平上调。用 APN 治疗可激活 AMPK，增加 eNOS 的表达并减弱 iNOS 的表达。本研究表明，APN 通过其抗炎、抗氧化应激和抗凋亡作用对 LIRI 发挥保护作用。在 2 型糖尿病大鼠中，APN 的这些保护作用被消除，导致 LIRI 加重。本研究表明，APN 可能是 2 型糖尿病合并 LIRI 的潜在治疗药物。
