title: Inhibition of complement C3 might rescue vascular hyporeactivity in a conscious hemorrhagic shock rat model.
abstract: BACKGROUND
  Vascular hyporeactivity in severe hemorrhagic shock could induce refractory hypotension and is an important cause of death. The global acute inflammatory response induced in shock triggers the over-expression of reactive oxygen species, NO, ET1 and TNF-α, which play essential roles in the pathology of vascular hyporeactivity. This leads to a hypothesis that inhibition of the complement system, the mediator of the inflammatory cascade, might be a promising therapeutic exploration for vascular hyporeactivity.
  
  
  METHODS
  We use cobra venom factor (CVF) and the soluble form of CR1 (sCR1) which deplete or inhibit complement C3 respectively to examine its role in vascular hyporeactivity in a conscious hemorrhagic shock rat model.
  
  
  RESULTS
  We first confirmed the over-activation of C3 during shock and the down-regulation effects of CVF and sCR1 on C3. Then, both CVF and sCR1 could significantly mitigate the over-expression of serum NO, ET-1, TNF-α and reactive oxygen species. Finally, the vascular reactivity of superior mesenteric arteries (SMA) was examined in vitro, which confirmed the massive reduction of vascular reactivity in shock, which was significantly rescued by both CVF and sCR1.
  
  
  CONCLUSIONS
  Inhibition of C3 might improve the reactivity of SMA to norepinephrine during hemorrhagic shock possibly through the downregulation of NO, ET1, TNF-α and reactive oxygen radicals.
authors.affiliation: Department of Emergency, Wuhan Union Hospital affiliated with Tongji Medical College, Huazhong University of Science and Technology, PR China. Electronic address: dchenjx@gmail.com.
authors.forename: Ding
authors.initials: D
authors.lastname: Chen
authors.affiliation: Department of Emergency, Wuhan Union Hospital affiliated with Tongji Medical College, Huazhong University of Science and Technology, PR China. Electronic address: smengqi@126.com.
authors.forename: Meng-Qi
authors.initials: MQ
authors.lastname: Song
authors.affiliation: Department of Emergency, Wuhan Union Hospital affiliated with Tongji Medical College, Huazhong University of Science and Technology, PR China. Electronic address: yan122223@163.com.
authors.forename: Yan-Jun
authors.initials: YJ
authors.lastname: Liu
authors.affiliation: Department of Emergency, Wuhan Union Hospital affiliated with Tongji Medical College, Huazhong University of Science and Technology, PR China. Electronic address: renkai8@yeah.net.
authors.forename: Yin-Kai
authors.initials: YK
authors.lastname: Xue
authors.affiliation: Department of Emergency, Wuhan Union Hospital affiliated with Tongji Medical College, Huazhong University of Science and Technology, PR China. Electronic address: pingc688@126.com.
authors.forename: Ping
authors.initials: P
authors.lastname: Cheng
authors.affiliation: Department of Emergency, Wuhan Union Hospital affiliated with Tongji Medical College, Huazhong University of Science and Technology, PR China. Electronic address: zhenghai999@126.com.
authors.forename: Hai
authors.initials: H
authors.lastname: Zheng
authors.affiliation: Department of Emergency, Wuhan Union Hospital affiliated with Tongji Medical College, Huazhong University of Science and Technology, PR China. Electronic address: Li-BoChen@outlook.com.
authors.forename: Li-Bo
authors.initials: LB
authors.lastname: Chen
mesh_terms: D000818:Animals; D003167:Complement Activation / Q000187:drug effects*; D003176:Complement C3 / Q000037:antagonists & inhibitors* / Q000378:metabolism; D051056:Complement Inactivating Agents / Q000008:administration & dosage* / Q000378:metabolism; D004195:Disease Models, Animal; D004546:Elapid Venoms / Q000008:administration & dosage*; D019332:Endothelin-1 / Q000097:blood; D017538:Mesenteric Artery, Superior / Q000187:drug effects* / Q000503:physiopathology; D009569:Nitric Oxide / Q000097:blood; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species / Q000097:blood; D017463:Receptors, Complement 3b / Q000008:administration & dosage* / Q000378:metabolism; D012771:Shock, Hemorrhagic / Q000188:drug therapy* / Q000209:etiology / Q000503:physiopathology; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000097:blood; D014661:Vasoconstriction / Q000187:drug effects*; D014662:Vasoconstrictor Agents / Q000008:administration & dosage* / Q000378:metabolism*
chemical_list: D003176:Complement C3; D051056:Complement Inactivating Agents; D004546:Elapid Venoms; D019332:Endothelin-1; D017382:Reactive Oxygen Species; D017463:Receptors, Complement 3b; D014409:Tumor Necrosis Factor-alpha; D014662:Vasoconstrictor Agents; C016310:cobra venom factor; D009569:Nitric Oxide
keywords: Complement; Hemorrhagic shock; Vascular reactivity