Department of Surgery, Chang Gung Memorial Hospital at Linkou, Chang Gung University College of Medicine, 5, Fushing Street, Kweishan Shiang, Taoyuan 333, Taiwan.
Injury. 2011 Jul;42(7):638-42. doi: 10.1016/j.injury.2010.07.242. Epub 2010 Aug 14.
The phosphoinositide 3-kinase (PI3K)/protein kinase B (Akt) is known to be an endogenous negative feedback or compensatory mechanism that serves to limit pro-inflammatory and chemotactic events in response to injury. The aim of this study is to elucidate whether Akt plays any role in 17β-estradiol (E2)-mediated attenuation of lung injury after acute pancreatitis (AP).
Male Sprague-Dawley rats underwent cerulein-induced AP. Rats were treated with vehicle (cyclodextrin), E2 (1 mg/kg body weight [BW]), or E2 plus PI3K/Akt inhibitor Wortmannin (100 μg/kg BW) 1h after the onset of AP. At 8 h after sham operation or AP, various parameters were measured.
AP led to a significant decrease in lung Akt phosphorylation, which was associated with increased lung tissue myeloperoxidase (MPO) activity, wet-to-dry weight ratios, interleukin (IL)-6, tumor necrosis factor (TNF)-α, cytokine-induced neutrophil chemoattractant (CINC)-1, and CINC-3 levels. Administration of E2 after AP restored the AP-induced decrease in Akt phosphorylation and attenuated the increase in lung injury markers (MPO activity and wet-to dry weight ratios) and pro-inflammatory mediator production. The effects of E2 on the lung were abolished by co-administration of Wortmannin.
These results collectively suggest evidences that the Akt pathway seems to be required for E2-mediated protection of lung injury after AP.
磷酸肌醇 3-激酶（PI3K）/蛋白激酶 B（Akt）是一种内源性负反馈或补偿机制，可限制损伤后炎症和趋化作用的发生。本研究旨在阐明 Akt 是否在 17β-雌二醇（E2）介导的急性胰腺炎（AP）后肺损伤减轻中发挥作用。
雄性 Sprague-Dawley 大鼠接受 Cerulein 诱导的 AP。AP 发作后 1 小时，大鼠用载体（环糊精）、E2（1mg/kg 体重）或 E2 加 PI3K/Akt 抑制剂 Wortmannin（100μg/kg BW）处理。假手术或 AP 后 8 小时，测量各种参数。
AP 导致肺 Akt 磷酸化明显下降，与肺组织髓过氧化物酶（MPO）活性、湿重/干重比、白细胞介素（IL）-6、肿瘤坏死因子（TNF）-α、细胞因子诱导的中性粒细胞趋化因子（CINC）-1 和 CINC-3 水平升高相关。AP 后给予 E2 可恢复 AP 诱导的 Akt 磷酸化下降，并减轻肺损伤标志物（MPO 活性和湿重/干重比）和促炎介质产生的增加。同时给予 Wortmannin 可消除 E2 对肺的作用。
这些结果共同表明 Akt 途径似乎是 E2 介导的 AP 后肺损伤保护所必需的。
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