PMID- 24796746 OWN - NLM STAT- MEDLINE DCOM- 20141027 LR - 20161125 IS - 1007-8738 (Print) IS - 1007-8738 (Linking) VI - 30 IP - 5 DP - 2014 May TI - [Mechanism of cardiac function changes in rat models of Sjogren's syndrome based on Keap1-Nrf2/ARE signaling pathways]. PG - 497-501 AB - 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), gamma-glutamic acid and a half long glycine synthetase (gamma-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, gamma-GCS protein expressions in the heart tissue, while TrX, GSH, IL-5 and SOD levels decreased significantly (P<0.01). CONCLUSION: The immune imbalance in SS rats may be related with the up-regulated levels of Keap1, Maf, Nfr2 mRNAs, HO-1, gamma-GCS. FAU - Wang, Fang AU - Wang F AD - Anhui University of Traditional Chinese Medicine, Hefei 230031, China. FAU - Liu, Jian AU - Liu J AD - First Affiliated Hospital of Anhui University of Traditional Chinese Medicine, Hefei 230031, China. FAU - Ye, Yingfa AU - Ye Y AD - Anhui University of Traditional Chinese Medicine, Hefei 230031, China. FAU - Zhang, Xiaojun AU - Zhang X AD - Anhui University of Traditional Chinese Medicine, Hefei 230031; Hubei University of Chinese Medicine, Wuhan 430065, China. FAU - Wan, Lei AU - Wan L AD - First Affiliated Hospital of Anhui University of Traditional Chinese Medicine, Hefei 230031, China. LA - chi PT - Journal Article PL - China TA - Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi JT - Xi bao yu fen zi mian yi xue za zhi = Chinese journal of cellular and molecular immunology JID - 101139110 RN - 0 (Antioxidants) RN - 0 (Interleukin-18) RN - 0 (Intracellular Signaling Peptides and Proteins) RN - 0 (KEAP1 protein, rat) RN - 0 (Kelch-Like ECH-Associated Protein 1) RN - 0 (NF-E2-Related Factor 2) RN - 0 (Nfe2l2 protein, rat) RN - 0 (Reactive Oxygen Species) RN - 4Y8F71G49Q (Malondialdehyde) RN - 52500-60-4 (Thioredoxins) RN - EC 1.14.14.18 (Heme Oxygenase-1) RN - EC 1.15.1.1 (Superoxide Dismutase) RN - EC 6.3.2.2 (Glutamate-Cysteine Ligase) RN - GAN16C9B8O (Glutathione) SB - IM MH - Animals MH - Antioxidants/metabolism/pharmacology MH - Blotting, Western MH - Disease Models, Animal MH - Gene Expression MH - Glutamate-Cysteine Ligase/metabolism MH - Glutathione/metabolism MH - Heart/*physiopathology MH - Heme Oxygenase-1/metabolism MH - Immunohistochemistry MH - Interleukin-18/metabolism MH - Intracellular Signaling Peptides and Proteins/*genetics MH - Kelch-Like ECH-Associated Protein 1 MH - Male MH - Malondialdehyde/metabolism MH - NF-E2-Related Factor 2/*genetics MH - Rats MH - Rats, Wistar MH - Reactive Oxygen Species/metabolism MH - Response Elements/genetics MH - Reverse Transcriptase Polymerase Chain Reaction MH - Signal Transduction/*genetics MH - Sjogren's Syndrome/*genetics/metabolism/physiopathology MH - Superoxide Dismutase/metabolism MH - Thioredoxins/metabolism EDAT- 2014/05/07 06:00 MHDA- 2014/10/28 06:00 CRDT- 2014/05/07 06:00 PHST- 2014/05/07 06:00 [entrez] PHST- 2014/05/07 06:00 [pubmed] PHST- 2014/10/28 06:00 [medline] PST - ppublish SO - Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi. 2014 May;30(5):497-501.