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Chinese Journal of Clinical Pharmacology and Therapeutics ›› 2012, Vol. 17 ›› Issue (2): 159-163.

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Protective effects of ERK1/2 inhibitor PD98059 on multiple organ dysfunction in disseminated- intravascular-coagulation rat

ZHU Hai-long, ZHANG Gen-bao, LI Wei, ZHANG Cui   

  1. Department of Pathophysilogy, Wannan Medical College, Wuhu 241002, Anhui, China
  • Received:2011-10-18 Revised:2011-11-24 Online:2012-02-26 Published:2012-03-12

Abstract: AIM: To investigate the protective effects of extracellular signal-regulated kinase 1/2 (ERK1/2) inhibitor PD98059 on multiple organ dysfunction in endotoxin-induced disseminated-intravascular- coagulation (DIC) rat.METHODS: Sprague-Dawley rats were divided randomly into 3 groups: control group, DIC group and inhibitor group. The endotoxin-induced DIC rat model was established with LPS (6 mg/kg) by intraperitoneal injection. Inbibitor group were injected with LPS (6 mg/kg) and PD98059 (10 mg/kg). The blood sample was taken after 5 h to detect APTT, FIB, LDH, ALP, ALT, AST, BUN and Cr by MC-2000 coagulation autoanalyzer and Olympus biochemical autoanalyzer; and then take out the heart, liver, kidney and observe pathology change of the tissue section.RESULTS: Compared with control group: experimental data from DIC group indicated that APTT, LDH, ALP, ALT, AST, BUN and Cr obviously extended or increased (P<0.01), while FIB reduced (P<0.01). Heart, liver and kidney biopsy showed vascular engorgement. Except for Cr, all the laboratory indexes ameliorated among inhibitor group than DIC group (P<0.01), while pathological change was alleviated in heart, liver and kidney.CONCLUSION: This study shows that PD98059 can attenuate multiple organ dysfunction in the pathogenesis in endotoxin-induced DIC rat, and the mechanism involves ERK1/2 inhibition.

Key words: Extracellular signal-regulated kinase 1/2, Lipopolysaccharide, Disseminated intravascular coagulation

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