Abstract | BACKGROUND: Gut-derived mediators are carried via mesenteric lymph duct into systemic circulation after trauma/ hemorrhagic shock (T/HS), thus leading to acute lung injury (ALI)/ multiple-organ dysfunction syndrome. Phospholipase A2 (PLA(2)) is a key enzyme for the production of lipid mediators in posthemorrhagic shock mesenteric lymph (PHSML). However, the precise functions of PLA(2) subtype, such as cytosolic PLA(2), secretory PLA(2), and Ca-independent PLA(2), in the acute phase of inflammation have remained unclear. Our previous study has suggested that the activation of Group VIB Ca-independent PLA(2γ) (PLA(2γ)) may be associated with increased lyso- phosphatidylcholines (LPCs) in the PHSML. Therefore, our purpose was to verify the role of iPLA(2γ) on the production of 2-polyunsaturated LPC species and the pathogenesis of T/HS-induced ALI using an iPLA(2γ)-specific inhibitor, R-(E)-6-(bromoethylene)-3-(1-naphthalenyl)-2H-tetrahydropyran-2-one (R-BEL). METHODS: Male Sprague-Dawley rats were anesthetized and cannulated in blood vessels and mesenteric lymph duct. Animals in the T/HS group underwent a midline laparotomy plus hemorrhagic shock (mean arterial pressure, 35 mm Hg, 30 minutes) and 2-hour resuscitation with shed blood and 2× normal saline. Trauma/ sham shock rats were performed the identical procedure without hemorrhage. R-BEL or DMSO was administered 30 minutes before T/HS or trauma/ sham shock. Polyunsaturated LPCs and arachidonic acid in the PHSML were analyzed with a liquid chromatography/electrospray ionization-mass spectrometry. Furthermore, ALI was assessed by lung vascular permeability, myeloperoxidase activity, and histology. RESULTS: T/HS increased 2-polyunsaturated LPCs and arachidonic acid in the PHSML. The R-BEL pretreatment significantly decreased these lipids and also inhibited ALI. CONCLUSION: The iPLA(2γ) enzyme is possibly involved in the pathogenesis of ALI following T/HS through the mesenteric lymph pathway.
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Authors | Koji Morishita, Junichi Aiboshi, Tetsuyuki Kobayashi, Yuri Yokoyama, Saori Mikami, Jiro Kumagai, Keiko Onisawa, Yasuhiro Otomo |
Journal | The journal of trauma and acute care surgery
(J Trauma Acute Care Surg)
Vol. 75
Issue 5
Pg. 767-74
(Nov 2013)
ISSN: 2163-0763 [Electronic] United States |
PMID | 24158193
(Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Group IV Phospholipases A2
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Topics |
- Acute Lung Injury
(enzymology, etiology, therapy)
- Animals
- Disease Models, Animal
- Group IV Phospholipases A2
(metabolism)
- Male
- Rats
- Rats, Sprague-Dawley
- Resuscitation
- Shock, Hemorrhagic
(complications, metabolism, therapy)
- Wounds and Injuries
(complications, metabolism)
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