title: Pivotal role of mast cell carboxypeptidase A in mediating protection against small intestinal ischemia-reperfusion injury in rats after ischemic preconditioning.
abstract: OBJECTIVE
  Mast cell (MC) degranulation contributes to the protection mediated by ischemic preconditioning (IPC); however, the precise mechanisms underlying this protection remain largely unknown. Mast cell carboxypeptidase A (MC-CPA) is released solely from MCs and plays a critical role in degrading toxins and endothelin 1 (ET-1). The present study sought to explore whether MC-CPA is involved in the process of IPC in a rodent model of small intestinal ischemia reperfusion (IIR) injury.
  
  
  METHODS
  IIR injuries were induced in Sprague-Dawley rats by clamping the superior mesenteric artery for 60 min followed by reperfusion for 2 h. One cycle of 10 min intestinal ischemia and 10 min of reperfusion was used in the IPC group, and the MC stabilizer cromolyn sodium and MC potato carboxypeptidase inhibitor were administered before the start of IPC. At the end of experiment, intestine tissue was obtained for assays of the MC-CPA3, tumor necrosis factor-α, interleukin-6, and ET-1 contents and myeloperoxidase activities. Intestinal histologic injury scores and MC degranulation were assessed. Apoptosis indices and cleaved caspase- 3 protein expressions were quantified.
  
  
  RESULTS
  IIR resulted in severe injury, as evidenced by significant increases in injury scores and MC-CPA3, tumor necrosis factor-α, interleukin-6, and ET-1 contents that were accompanied with concomitant elevations in cleaved caspase 3 expression, apoptosis indices, and myeloperoxidase activities. IPC induced a significant increase in MC-CPA3, induced MC degranulation, and attenuated IIR injury by downregulating IIR-induced biochemical changes, whereas cromolyn sodium and potato carboxypeptidase inhibitor abolished the IPC-mediated changes.
  
  
  CONCLUSIONS
  These data suggest that IPC protected against IIR injury via the MC degranulation-mediated release of MC-CPA.
authors: Department of Anesthesiology, The Third Affiliated Hospital, Sun Yat-sen University, Guangzhou, China.
authors: Dandan
authors: D
authors: Xing
authors: Department of Anesthesiology, The Third Affiliated Hospital, Sun Yat-sen University, Guangzhou, China.
authors: Rui
authors: R
authors: Zhang
authors: Department of Anesthesiology, The Third Affiliated Hospital, Sun Yat-sen University, Guangzhou, China.
authors: Shun
authors: S
authors: Li
authors: Department of Anesthesiology, The Third Affiliated Hospital, Sun Yat-sen University, Guangzhou, China.
authors: Pinjie
authors: P
authors: Huang
authors: Department of Anesthesiology, The Third Affiliated Hospital, Sun Yat-sen University, Guangzhou, China.
authors: Chenfang
authors: C
authors: Luo
authors: Department of Anesthesiology, The Third Affiliated Hospital, Sun Yat-sen University, Guangzhou, China.
authors: Ziqing
authors: Z
authors: Hei
authors: Department of Anesthesiology, University of Hong Kong, Hong Kong, China.
authors: Zhengyuan
authors: Z
authors: Xia
authors: Department of Anesthesiology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou, China. Electronic address: ganxiaoliang@yeah.net.
authors: Xiaoliang
authors: X
authors: Gan
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000502:physiology; D043422:Carboxypeptidases A / Q000378:metabolism*; D015550:Cell Degranulation / Q000502:physiology; D019332:Endothelin-1 / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D007413:Intestinal Mucosa / Q000378:metabolism* / Q000473:pathology; D007421:Intestine, Small / Q000378:metabolism / Q000473:pathology; D019194:Ischemic Preconditioning / Q000379:methods*; D008297:Male; D008407:Mast Cells / Q000201:enzymology*; D009195:Peroxidase / Q000378:metabolism; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000378:metabolism* / Q000473:pathology / Q000628:therapy*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D019332:Endothelin-1; D015850:Interleukin-6; D014409:Tumor Necrosis Factor-alpha; D009195:Peroxidase; D043422:Carboxypeptidases A; C000593420:mast cell carboxypeptidase A, rat
keywords: Carboxypeptidase A; Mast cell; Preconditioning; Reperfusion injury; Small intestinal ischemia