title: Monocytes, endoplasmic reticulum stress and metabolomics in dogs with multiple organ dysfunction syndrome treated by continuous venovenous hemodiafiltration.
abstract: OBJECTIVE
  We tried to investigate the mechanism of continuous venovenous hemodiafiltration (CVVHDF) treatment in monocytes function, endoplasmic reticulum (ER) stress signaling pathways, metabolomics and histopathological changes of MODS dogs, and aimed to enhance the understanding of pathogenesis and provide novel avenues to potential therapies.
  
  
  METHODS
  12 male Beagle dogs were used to develop the stable models of MODS by using hemorrhagic shock plus resuscitation and endotoxemia, and assigned randomly to CVVHDF group (n=6) and MODS group (n=6). The dogs in CVVHDF group were given the typical CVVHDF treatment for 24h after the completion of endotoxin intravenous infusion, while those in MODS group were offered the i.v heparin instead only. Serum sample were collected at five time points, i.e. before anesthesia, 0h, 6h, 12h and 24h after the endotoxin injection (T1~T5, respectively), and meanwhile, the changes of mRNA, protein and human umbilical vein endothelial cells (HUVECs) apoptosis rates in JNK, CHOP and Caspase-12 were observed before and after interfered by RNA interference technology.
  
  
  RESULTS
  The levels of DLA-DR, IL-1β and IL-4 were higher than those in MODS group after the CVVHDF treatment, and the early and late apoptosis rates showed downward trend compared with MODS group. In vitro and prior to RNA interference (RNAi), the levels of mRNA and protein expression and HUVECs apoptosis rates of JNK, CHOP and Caspase-12 in CVVHDF group were significantly lower compared to T1 and MODS group respectively. However, the levels of mRNA and protein expression and HUVECs apoptosis rates were significantly lower than those before interfered by RNAi in both two groups. The serum levels of LPCs, ornithine, proline, methionine, etc. were down-regulated while carnitines, FFAs, PC, etc. were increased significantly in MODS (T4), and the serum levels of methionine, proline, arginine and lysine were increased while carnitine, LPCs, PCs, SMs and orthophosporic acid were decreased after 12 hours CVVHDF treatment (T4).
  
  
  CONCLUSIONS
  CVVHDF treatment could reduce the apoptosis of the cells by enhancing the antigen presentation, improving the anti-inflammatory and proinflammatory imbalance and even correcting the metabolic disorder of amino acids and phospholipids.
authors.affiliation: Department of Nephropathy, The First Affiliated Hospital of Xinjiang Medical University, Urumqi, Xinjiang Uygur Autonomous Region of China, China.
authors.forename: Yun-Peng
authors.initials: YP
authors.lastname: Xu
authors.affiliation: Department of Nephropathy, The First Affiliated Hospital of Xinjiang Medical University, Urumqi, Xinjiang Uygur Autonomous Region of China, China.
authors.forename: Xiao-Lu
authors.initials: XL
authors.lastname: Sui
authors.affiliation: Department of Nephropathy, The First Affiliated Hospital of Xinjiang Medical University, Urumqi, Xinjiang Uygur Autonomous Region of China, China.
authors.forename: Ai-Sha
authors.initials: AS
authors.lastname: Zhang
authors.affiliation: Department of Nephropathy, The First Affiliated Hospital of Xinjiang Medical University, Urumqi, Xinjiang Uygur Autonomous Region of China, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Ye
authors.affiliation: Department of Nephropathy, The First Affiliated Hospital of Xinjiang Medical University, Urumqi, Xinjiang Uygur Autonomous Region of China, China.
authors.forename: Feng-Juan
authors.initials: FJ
authors.lastname: Gu
authors.affiliation: Department of Nephropathy, The First Affiliated Hospital of Xinjiang Medical University, Urumqi, Xinjiang Uygur Autonomous Region of China, China.
authors.forename: Ji-Hong
authors.initials: JH
authors.lastname: Chen
mesh_terms: D000818:Animals; D053454:Caspase 12 / Q000235:genetics / Q000378:metabolism; D002470:Cell Survival; D004195:Disease Models, Animal; D004285:Dogs; D059865:Endoplasmic Reticulum Stress; D005786:Gene Expression Regulation / Q000187:drug effects; D017583:Hemodiafiltration / Q000379:methods*; D006493:Heparin / Q000008:administration & dosage* / Q000494:pharmacology; D061307:Human Umbilical Vein Endothelial Cells; D006801:Humans; D048670:MAP Kinase Kinase 4 / Q000235:genetics / Q000378:metabolism; D008297:Male; D055432:Metabolomics / Q000379:methods*; D008715:Methionine / Q000097:blood; D009000:Monocytes / Q000187:drug effects / Q000378:metabolism*; D009102:Multiple Organ Failure / Q000097:blood / Q000235:genetics / Q000378:metabolism / Q000628:therapy*; D009952:Ornithine / Q000097:blood; D011392:Proline / Q000097:blood; D011897:Random Allocation; D051742:Transcription Factor CHOP / Q000235:genetics / Q000378:metabolism
chemical_list: D051742:Transcription Factor CHOP; D006493:Heparin; D011392:Proline; D008715:Methionine; D009952:Ornithine; D048670:MAP Kinase Kinase 4; D053454:Caspase 12
keywords: continuous venovenous hemodiafiltration (CVVHDF); endoplasmic reticulum stress; metabolomics; monocytes; multiple organ dysfunction syndrome (MODS)