title: Clopidogrel reduces the inflammatory response of lung in a rat model of decompression sickness.
abstract: Inflammation and platelet activation are critical phenomena in the setting of decompression sickness. Clopidogrel (Clo) inhibits platelet activation and may also reduce inflammation. The goal of this study was to investigate if Clo had a protective role in decompression sickness (DCS) through anti-inflammation way. Male Sprague-Dawley rats (n=111) were assigned to three groups: control+vehicle group, DCS+vehicle, DCS+Clo group. The experimental group received 50 mg/kg of Clo or vehicle for 3 days, then compressed to 1,600 kPa (150 msw) in 28 s, maintained at 150 msw for 242 s and decompressed to surface at 3m/s. In a control experiment, rats were also treated with vehicle for 3 days and maintained at atmospheric pressure for an equivalent period of time. Clinical assessment took place over a period of 30 min after surfacing. At the end, blood samples were collected for blood cells counts and cytokine detection. The pathology and the wet/dry ratio of lung tissues, immunohistochemical detection of lung tissue CD41 expression, the numbers of P-selectin positive platelets and platelet-leukocyte conjugates in blood were tested. We found that Clo significantly reduced the DCS mortality risk (mortality rate: 11/45 with Clo vs. 28/46 in the untreated group, P<0.01). Clo reduced the lung injury, the wet/dry ratio of lung, the accumulation of platelet and leukocyte in lung, the fall in platelet count, the WBC count, the numbers of activated platelets and platelet-leukocyte complexes in peripheral blood. It was concluded that Clo can play a protective role in decompression sickness through reducing post-decompression platelet activation and inflammatory process.
authors.affiliation: Department of Diving Medicine, Institute of Naval Medical Research, Shanghai 200433, China.
authors.forename: Xiao-Chen
authors.initials: XC
authors.lastname: Bao
authors.affiliation: Health Testing Center, General Naval Hospital, Beijing, 100048, China.
authors.forename: Hong
authors.initials: H
authors.lastname: Chen
authors.affiliation: Department of Diving Medicine, Institute of Naval Medical Research, Shanghai 200433, China. Electronic address: zhouqybb@gmail.com.
authors.forename: Yi-Qun
authors.initials: YQ
authors.lastname: Fang
authors.affiliation: Department of Diving Medicine, Institute of Naval Medical Research, Shanghai 200433, China.
authors.forename: Heng-Rong
authors.initials: HR
authors.lastname: Yuan
authors.affiliation: Department of Diving Medicine, Institute of Naval Medical Research, Shanghai 200433, China.
authors.forename: Pu
authors.initials: P
authors.lastname: You
authors.affiliation: Department of Diving Medicine, Institute of Naval Medical Research, Shanghai 200433, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Ma
authors.affiliation: Department of Diving Medicine, Institute of Naval Medical Research, Shanghai 200433, China.
authors.forename: Fang-Fang
authors.initials: FF
authors.lastname: Wang
mesh_terms: D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D001792:Blood Platelets / Q000187:drug effects / Q000276:immunology; D000077144:Clopidogrel; D016207:Cytokines / Q000378:metabolism; D003665:Decompression Sickness / Q000097:blood / Q000188:drug therapy* / Q000276:immunology* / Q000473:pathology; D004195:Disease Models, Animal; D007150:Immunohistochemistry; D007962:Leukocytes / Q000187:drug effects / Q000502:physiology; D008168:Lung / Q000187:drug effects* / Q000276:immunology* / Q000473:pathology; D008297:Male; D009929:Organ Size; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology; D040201:Platelet Membrane Glycoprotein IIb / Q000378:metabolism; D011312:Pressure; D017207:Rats, Sprague-Dawley; D013988:Ticlopidine / Q000031:analogs & derivatives* / Q000494:pharmacology; D016896:Treatment Outcome
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D016207:Cytokines; D010975:Platelet Aggregation Inhibitors; D040201:Platelet Membrane Glycoprotein IIb; D000077144:Clopidogrel; D013988:Ticlopidine
keywords: Decompression sickness; Inflammation; Platelet activation