title: Triptolide ameliorates lipopolysaccharide-induced acute lung injury in rats.
abstract: BACKGROUND
  Acute lung injury (ALI) is a serious clinical syndrome with a high rate of mortality. In this study, the effects of triptolide on lipopolysaccharide (LPS)-induced ALI in rats were investigated.
  
  
  METHODS
  Sixty-five male Sprague Dawley rats(approved by ethics committee of the First Affiliated Hospital of Soochow University) were randomly divided into five groups. The control group was injected with 2.5 mL saline/kg body weight via the tail vein and intraperitoneally with 1% dimethyl sulfoxide (DMSO) (n = 5). The L group was administered with 0.2% LPS dissolved in saline (5 mg/kg) to induce ALI via the tail vein (n = 15). The TP1, TP2, and TP3 groups were treated as rats in the L group and then intraperitoneally injected with 25, 50, and 100 μg triptolide/kg body weight, respectively (15 rats per group). Blood samples from the left heart artery were taken for blood gas analysis at 1 hour before injection and at 1, 3, 6, and 12 hours after saline and DMSO administration in the control group, LPS injection in the L group, and triptolide injection in the TP1, TP2, and TP3 groups. Lung wet-to-dry weight (W/D) ratio, diffuse alveolar damage (DAD) score, TNF-α levels, and mRNA and protein expression of toll-like receptor 4 (TLR4) were analyzed.
  
  
  RESULTS
  Compared with the control group, the arterial partial pressure of oxygen (PaO2) declined (P <0.05), the W/D ratio and DAD score increased (P <0.05), and TNF-α levels in serum and bronchoalveolar lavage fluid (BALF) and mRNA and protein expression of TLR4 were significantly increased in the L group (P <0.05). Compared with the L group, PaO2 significantly increased in the TP2 and TP3 groups (P <0.05), while the W/D ratio and DAD score were significantly decreased in the TP2 and TP3 groups (P <0.05). TNF-α levels and mRNA and protein expression of TLR4 were significantly decreased in the TP2 and TP3 groups compared with the L group (P <0.05).
  
  
  CONCLUSIONS
  Triptolide can ameliorate LPS-induced ALI by reducing the release of the inflammatory mediator TNF-α and inhibiting TLR4 expression.
authors.forename: Jianling
authors.initials: J
authors.lastname: Gao
authors.forename: Ying
authors.initials: Y
authors.lastname: Zhan
authors.forename: Jun
authors.initials: J
authors.lastname: Chen
authors.forename: Lina
authors.initials: L
authors.lastname: Wang
authors.affiliation: Department of Anesthesiology, First Affiliated Hospital of Soochow University, Shizi Street 188, Suzhou, Jiangsu 215006, China. jianpingyangsz@hotmail.com.
authors.forename: Jianping
authors.initials: J
authors.lastname: Yang
mesh_terms: D055371:Acute Lung Injury / Q000097:blood / Q000188:drug therapy* / Q000235:genetics / Q000517:prevention & control*; D000818:Animals; D001992:Bronchoalveolar Lavage Fluid; D002245:Carbon Dioxide / Q000378:metabolism; D004224:Diterpenes / Q000494:pharmacology / Q000627:therapeutic use*; D004852:Epoxy Compounds / Q000494:pharmacology / Q000627:therapeutic use; D005786:Gene Expression Regulation / Q000187:drug effects; D006863:Hydrogen-Ion Concentration / Q000187:drug effects; D008070:Lipopolysaccharides; D008297:Male; D009929:Organ Size / Q000187:drug effects; D010100:Oxygen / Q000378:metabolism; D010313:Partial Pressure; D010616:Phenanthrenes / Q000494:pharmacology / Q000627:therapeutic use*; D011650:Pulmonary Alveoli / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D051197:Toll-Like Receptor 4 / Q000235:genetics / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000097:blood
chemical_list: D004224:Diterpenes; D004852:Epoxy Compounds; D008070:Lipopolysaccharides; D010616:Phenanthrenes; D012333:RNA, Messenger; D051197:Toll-Like Receptor 4; D014409:Tumor Necrosis Factor-alpha; D002245:Carbon Dioxide; C001899:triptolide; D010100:Oxygen