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A Journal on Internal Medicine
Indexed/Abstracted in: BIOSIS Previews, Current Contents/Clinical Medicine, EMBASE, PubMed/MEDLINE, Science Citation Index Expanded (SciSearch), Scopus
Impact Factor 1,6
Panminerva Medica 2014 March;56(1):49-55
Mechanism of ulinastatin protection against lung injury caused by lower limb ischemia-reperfusion
Yu L. 1, Luo Q. 2, Fang H. 1, 3 ✉
1 Department of Anesthesiology, Zhongshan Hospital, Fudan University, Shanghai, China;
2 Department of Anesthesiology, Obstetrics and Gynecology Hospital, Fudan University, Shanghai, China;
3 Department of Anesthesiology, Jinshan Hospital, Fudan University, Shanghai, China
Aim: The aim of this paper was to investigate the mechanism of ulinastatin’s protection of lung from injury caused by lower limb ischemia-reperfusion in a rat model.
Methods: Male, Sprague-Dawley rats were divided into three groups: saline control (CON), lung injury group, caused by lower limb ischemia-reperfusion (LIR) by rubber band ligation of the lower limbs for 3 h, followed by reperfusion for 3 h and lung injury with ulinastatin pretreatment intravenously before ligation (UTI). Carotid arterial blood was drawn 3 h postreperfusion for gas analysis, and alveolar lavage of one lung was performed. Rats were then sacrificed and lungs were taken for pathological examination and to detect phosphorylated and total p38, JNK, ERK levels. Inflammatory cell count and cytokines TNF-α, IL-1, IL-6 were measured from the lavage fluid.
Results: There was significant inflammatory cell infiltration, hemorrhaging, and edema of the lung in the LIR group, all of which were reduced significantly in the UTI group. Oxygenation index in the LIR was lower than the CON while it was higher in the UTI than the LIR group. Compared to the CON group, white blood cell count in the alveolar lavage fluid from LIR group was increased, while this is lower in the UTI. Lavage fluid TNF-α, IL-β, and IL-6 levels were higher in the LIR group than the CON group, and were significantly lower in the UTI than the LIR. LIR group exhibited increased phosphorylated ERK, JNK and p38; UTI group rats also had enhanced p-ERK levels, but had decreased p-p38 and p-JNK.
Conclusion: Ulinastatin pre-treatment reduces lung injury caused by lower limb ischemia-reperfusion via a mechanism that may involve inhibition of inflammatory cytokine production via p-JNK and p-p38 pathways.