title: Neuroprotection of tanshinone IIA against cerebral ischemia/reperfusion injury through inhibition of macrophage migration inhibitory factor in rats.
abstract: BACKGROUND
  Ischemia/reperfusion (I/R) injury is associated with systemic inflammatory response. Macrophage migration inhibitory factor (MIF) has been implicated in many inflammatory processes. Tanshinone IIA (TSA) is one of the active ingredients in danshen, which derived from the dried root or rhizome of Salviae miltiorrhizae Bge. Recent studies have demonstrated that TSA has protective effects against focal cerebral I/R injury. However, little is known about the underlying mechanisms. Here we put forward the hypothesis that TSA acts through inhibition of MIF expression during focal cerebral I/R injury in rats.
  
  
  RESULTS
  Rats were subjected to middle cerebral artery occlusion (MCAO) for 2 hours. This was followed by reperfusion. We measured neurological deficits, brain water content, and infarct volume, and found that neurological dysfunction, brain edema, and brain infarction were significantly attenuated by TSA 6 hours after reperfusion. We also measured myeloperoxidase (MPO) activity at 6 and 24 hours, and found that neutrophil infiltration was significantly higher in the vehicle+I/R group than in the TSA+I/R group. ELISA demonstrated that TSA could inhibit MIF expression and the release of TNF-α and IL-6 induced by I/R injury. Western blot analysis and immunofluorescence staining showed that MIF expression was significantly lower in the TSA+I/R group than in the vehicle+I/R group. MIF was found almost all located in neurons and hardly any located in astrocytes in the cerebral cortex. Western blot analysis and EMSA demonstrated that NF-κB expression and activity were significantly increased in the vehicle+I/R group. However, these changes were attenuated by TSA.
  
  
  CONCLUSIONS
  Our results suggest that TSA helps alleviate the proinflammatory responses associated with I/R-induced injury and that this neuroprotective effect may occur through down-regulation of MIF expression in neurons.
authors: Department of Pathology, Chongqing Medical University, Chongqing, People's Republic of China.
authors: Yanlin
authors: Y
authors: Chen
authors: Xuemei
authors: X
authors: Wu
authors: Shanshan
authors: S
authors: Yu
authors: Xuemei
authors: X
authors: Lin
authors: Jingxian
authors: J
authors: Wu
authors: Lan
authors: L
authors: Li
authors: Jing
authors: J
authors: Zhao
authors: Yong
authors: Y
authors: Zhao
mesh_terms: D045784:Abietanes / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use*; D000818:Animals; D034961:Antigens, Nuclear / Q000378:metabolism; D002545:Brain Ischemia / Q000150:complications / Q000188:drug therapy* / Q000201:enzymology / Q000473:pathology; D002544:Cerebral Infarction / Q000150:complications / Q000188:drug therapy / Q000201:enzymology / Q000473:pathology; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D018836:Inflammation Mediators / Q000378:metabolism; D019746:Intramolecular Oxidoreductases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D008263:Macrophage Migration-Inhibitory Factors / Q000037:antagonists & inhibitors* / Q000378:metabolism; D008297:Male; D009419:Nerve Tissue Proteins / Q000378:metabolism; D018696:Neuroprotective Agents / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use*; D020556:Neutrophil Infiltration / Q000187:drug effects; D009195:Peroxidase / Q000378:metabolism; D021381:Protein Transport / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000150:complications / Q000188:drug therapy* / Q000201:enzymology / Q000473:pathology; D013997:Time Factors; D051996:Transcription Factor RelA / Q000378:metabolism; D014867:Water
chemical_list: D045784:Abietanes; D034961:Antigens, Nuclear; D005904:Glial Fibrillary Acidic Protein; D018836:Inflammation Mediators; D008263:Macrophage Migration-Inhibitory Factors; D009419:Nerve Tissue Proteins; D018696:Neuroprotective Agents; C546339:Rbfox3 protein, rat; D051996:Transcription Factor RelA; C021751:tanshinone; D014867:Water; D009195:Peroxidase; D019746:Intramolecular Oxidoreductases; C515599:Mif protein, rat