title: [Mechanism of cardiac function changes in rat models of Sjogren's syndrome based on Keap1-Nrf2/ARE signaling pathways].
abstract: OBJECTIVE
  To investigate the mechanism underlying the changes in the cardiac function in rat models of Sjogren's syndrome (SS) based on Kelch-like ECH-associated protein 1 (Keap1)-Nrf2/ARE signaling pathways.
  
  
  METHODS
  Thirty male Wistar rats were randomly divided into two groups, normal control (NC) group and SS model group, with 15 in each. The rats in the model group were injected with the complete Freund's adjuvant plus homologous antigen of submandibular gland (0.2 mL mixture) into bilateral posterior paw metatarsus. The body mass, water intake, submandibular gland index, spleen index, and histological changes of the glands were observed 30 days after inflammation was induced. Cardiac function was assessed using invasive hemodynamic monitoring. Meanwhile, reactive oxygen species (ROS), malondialdehyde (MDA), superoxide dismutase (SOD) and total antioxidant capacity (TAC), IL-18, IL-35 were detected using ELISA; ROS and reactive nitrogen species (RNS), glutathione (GSH), thioredoxin (TrX) protein were determined using immunohistochemical staining. The expressions of Keap 1, nuclear factor erythroid 2-related factor (Nrf2), macrophage activating factor (Maf) antioxidant responsive element (ARE) mRNAs were detected using real-time fluorescent quantitative PCR (qRT-PCR); the levels of heme oxygenase-1 (HO-1), γ-glutamic acid and a half long glycine synthetase (γ-GCS) proteins in cardiac tissue were examined using Western blotting.
  
  
  RESULTS
  Compared with the NC group, the model group presented reduced body mass, submandibular gland index and spleen index (P<0.05), increased water intake (P<0.01), heart rate (HR), heart index (HI), left ventricular systolic pressure (LVSP) and left ventricular diastolic pressure (LVEDP) (P<0.05), and decreased left ventricular ±dp/dtmax (P<0.05). Compared with the NC group, the model group had increased IL-18, MDA, RNS, TAC, ROS levels, and Keap1, Maf, Nfr2 mRNAs, HO-1, γ-GCS protein expressions in the heart tissue, while TrX, GSH, IL-5 and SOD levels decreased significantly (P<0.01).
  
  
  CONCLUSIONS
  The immune imbalance in SS rats may be related with the up-regulated levels of Keap1, Maf, Nfr2 mRNAs, HO-1, γ-GCS.
authors.affiliation: Anhui University of Traditional Chinese Medicine, Hefei 230031, China.
authors.forename: Fang
authors.initials: F
authors.lastname: Wang
authors.affiliation: First Affiliated Hospital of Anhui University of Traditional Chinese Medicine, Hefei 230031, China.
authors.forename: Jian
authors.initials: J
authors.lastname: Liu
authors.affiliation: Anhui University of Traditional Chinese Medicine, Hefei 230031, China.
authors.forename: Yingfa
authors.initials: Y
authors.lastname: Ye
authors.affiliation: Anhui University of Traditional Chinese Medicine, Hefei 230031; Hubei University of Chinese Medicine, Wuhan 430065, China.
authors.forename: Xiaojun
authors.initials: X
authors.lastname: Zhang
authors.affiliation: First Affiliated Hospital of Anhui University of Traditional Chinese Medicine, Hefei 230031, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Wan
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000378:metabolism / Q000494:pharmacology; D015153:Blotting, Western; D004195:Disease Models, Animal; D015870:Gene Expression; D005721:Glutamate-Cysteine Ligase / Q000378:metabolism; D005978:Glutathione / Q000378:metabolism; D006321:Heart / Q000503:physiopathology*; D051547:Heme Oxygenase-1 / Q000378:metabolism; D007150:Immunohistochemistry; D020382:Interleukin-18 / Q000378:metabolism; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics*; D000072019:Kelch-Like ECH-Associated Protein 1; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D051267:NF-E2-Related Factor 2 / Q000235:genetics*; D051381:Rats; D017208:Rats, Wistar; D017382:Reactive Oxygen Species / Q000378:metabolism; D020218:Response Elements / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000235:genetics*; D012859:Sjogren's Syndrome / Q000235:genetics* / Q000378:metabolism / Q000503:physiopathology; D013482:Superoxide Dismutase / Q000378:metabolism; D013879:Thioredoxins / Q000378:metabolism
chemical_list: D000975:Antioxidants; D020382:Interleukin-18; D047908:Intracellular Signaling Peptides and Proteins; C486610:KEAP1 protein, rat; D000072019:Kelch-Like ECH-Associated Protein 1; D051267:NF-E2-Related Factor 2; C495637:Nfe2l2 protein, rat; D017382:Reactive Oxygen Species; D008315:Malondialdehyde; D013879:Thioredoxins; D051547:Heme Oxygenase-1; D013482:Superoxide Dismutase; D005721:Glutamate-Cysteine Ligase; D005978:Glutathione