Journal
ACTA PHARMACOLOGICA SINICA
Volume 33, Issue 10, Pages 1254-1259Publisher
ACTA PHARMACOLOGICA SINICA
DOI: 10.1038/aps.2012.84
Keywords
disseminated intravascular coagulation (DIC); lipopolysaccharides; tanshinone IIA; heparin; tumor necrosis factor-alpha
Funding
- National Natural Science Foundation of China [81000209]
- Chinese Ministry of Education [210255]
- Fundamental Research Funds for the Central Universities [21609304]
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Aim: To evaluate the effects of tanshinone IIA (Tan IIA), a lipophilic diterpene from the Chinese herb Salvia miltiorrhiza, on lipopolysaccharide (LPS)-induced disseminated intravascular coagulation (DIC) in rabbits. Methods: LPS-induced DIC model was made in adult male New Zealand rabbits by continuous intravenous infusion of LPS (0.5 mg/kg) via marginal ear vein for 6 h. The animals were simultaneously administered with Tan IIA (1, 3 and 10 mg/kg) or heparin (500 000 IU/kg) through continuous infusion via the contralateral marginal ear vein for 6 h. Before and 2 and 6 h after the start of LPS infusion, blood samples were taken for biochemical analyses. Results: Continuous infusion of LPS into the rabbits gradually impaired the hemostatic parameters, damaged renal and liver functions, increased the plasma TNF-alpha level, and led to a high mortality rate (80%). Treatment of the rabbits with Tan IIA dose-dependently attenuated the increase in activated partial thromboplastin time (APTT), prothrombin time (PT) and fibrin-fibrinogen degradation products (FDP); ameliorated the decrease in plasma levels of fibrinogen and platelets; and reversed the decline in activity of protein C and antithrombin III. Meanwhile, the treatment significantly suppressed the increase in the plasma levels of aminotransferase, creatinine and TNF-alpha, and led to much lower mortality (46.7% and 26.7% for the medium- and high-dose groups). Treatment of the rabbits with the high dose of heparin also effectively improved the hemostatic parameters, ameliorated liver and renal injuries, and reduced the plasma level of TNF-alpha, and significantly reduced the mortality (33.3%). Conclusion: Tan IIA exerts a protective effect against DIC in rabbits.
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