Intravenous injection of Tat-Rab GEF1 fusion protein attenuates lung injury induced by hepatic ischemia/reperfusion in mice
10.3969/j.issn.1000-4718.2019.02.024
- VernacularTitle:蛋白转导Rab GEF1减轻小鼠肝脏缺血再灌注所致的肺损伤
- Author:
Hong-Yi FANG
1
;
Nan CHENG
;
Han-Bin XIE
;
Chen-Fang LUO
Author Information
1. 中山大学附属第三医院麻醉科
- Keywords:
Hepatic ischemia/reperfusion;
Lung injury;
Mast cells;
Tat-RabGEF1 fusion protein;
Inflammation
- From:
Chinese Journal of Pathophysiology
2019;35(2):340-345
- CountryChina
- Language:Chinese
-
Abstract:
AIM:To investigate the effect of trans-activator of transcription-Rab guanine nucleotide exchange factor 1 (Tat-RabGEF1) fusion protein by intravenous injection on hepatic ischemia/reperfusion (IR) -induced lung injury, and its underlying mechanism.METHODS:Adult male C57BL/6 rats (n=24) were randomized into 3 groups with 8 rats each:sham group, IR group, and Tat-RabGEF1 group.IR was induced by occlusion of the vessels in the hepatic pedicle for 90 min followed by 4 h of reperfusion.The Tat-RabGEF1 protein was intravenously administered right after reperfusion through the caudal vein.The levels of tumor necrosis factor-α (TNF-α) , interleukin-6 (IL-6) and interleukin-1β (IL-1β) in bronchoalveolar lavage fluid (BALF) were assessed by ELISA.The lung histopathological injury score and lung wet/dry weight ratio were evaluated, and the levels ofβ-hexosaminidase A (β-Hex A) and myeloperoxidase (MPO) in the lung tissues were also measured.The expression of tryptase in the lung was determined by Western blot.RESULTS:The pathological changes after ischemia for 90 min followed by reperfusion for 4 h were significant, along with increased lung wet/dry weight ratio and lung injury score.Intravenous injection of Tat-RabGEF1 protein effectively alleviated the lung pathological injury (P<0.05).Compared with IR group, lower levels of TNF-α, IL-6 and IL-1βin BALF, and lower expression ofβ-Hex A, MPO and tryptase in the lung tissues in Tat-RabGEF1 group were observed (P<0.05).CONCLUSION:Intravenous injection of Tat-RabGEF1 protein attenuates the lung injury after IR, and its mechanism may be related with inhibition of mast cell activation, reduced releases ofβ-Hex A and tryptase, and decreased levels of TNF-α, IL-6, IL-1βand MPO.
