Akt pathway is required for oestrogen-mediated attenuation of lung injury in a rodent model of cerulein-induced acute pancreatitis

作者：Yang Shang Ju; Chen Han Ming; Hsieh Chi Hsun; Hsu Jun Te^*; Yeh Chun Nan; Yeh Ta Sen; Hwang Tsann Long; Jan Yi Yin; Chen Miin Fu

来源：Injury-International Journal of the Care of the Injured, 2011, 42(7): 638-642.

DOI：10.1016/j.injury.2010.07.242

• Acute pancreatitis
• Lung injury
• Oestrogen
• Akt
• Cytokines
• Chemokines
• MPO activity

Background: 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 17 beta-estradiol (E2)-mediated attenuation of lung injury after acute pancreatitis (AP).
Materials and methods: 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 mu g/kg BW) 1 h after the onset of AP. At 8 h after sham operation or AP, various parameters were measured.
Results: 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)-alpha, 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.
Conclusions: These results collectively suggest evidences that the Akt pathway seems to be required for E2-mediated protection of lung injury after AP.

• 出版日期2011-7
• 单位中国医科大学; 长春大学