细胞外信号调节激酶1/2抑制剂PD98059对弥散性血管内凝血大鼠多器官损伤的保护作用

中国临床药理学与治疗学 ›› 2012, Vol. 17 ›› Issue (2): 159-163.

细胞外信号调节激酶1/2抑制剂PD98059对弥散性血管内凝血大鼠多器官损伤的保护作用

朱海龙, 张根葆, 李伟, 张翠

皖南医学院病理生理学教研室,芜湖 241002,安徽

收稿日期:2011-10-18 修回日期:2011-11-24 出版日期:2012-02-26 发布日期:2012-03-12
通讯作者: 张根葆,男,教授,研究方向:心血管病理生理研究。E-mail: zgb858@163.com
作者简介:朱海龙,男,硕士,讲师,研究方向:心血管病理生理研究。Tel: 0553-3932476 E-mail: zhuhailong9850716@163.com
基金资助:
安徽省科技厅科技计划项目(10021303009);皖南医学院中青年科研基金(WK201016)

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

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

摘要/Abstract

摘要： 目的: 研究细胞外信号调节激酶1/2(ERK 1/2)抑制剂PD98059对大鼠内毒素弥散性血管内凝血(DIC)多器官损伤的保护作用。方法: Sprague-Dawley(SD)大鼠随机分为对照组、DIC组及抑制剂组。DIC组通过腹腔注射6 mg/kg 脂多糖 (LPS) 建立内毒素DIC模型,抑制剂组腹腔注射6 mg/kg LPS和10 mg/kg PD98059。5 h后取血,利用全自动血凝仪及生化仪检测活化部分凝血活酶时间(APTT)、纤维蛋白原(FIB)、乳酸脱氢酶(LDH)、碱性磷酸酶(ALP)、谷丙转氨酶(ALT)、谷草转氨酶(AST)、尿素(BUN)及肌酐(Cr)等指标;并留取心肝肾组织,光镜下观察其形态学变化。结果: 与对照组相比:DIC组APTT、LDH、ALP、ALT、AST、BUN及Cr均延长或升高(P＜0.01),FIB较对照组降低(P＜0.01),心、肝、肾组织病理学检查均有明显的血管扩张充血;PD98059预防性用药后,除Cr外各指标均有明显改善(P＜0.01),心、肝、肾组织血管充血减轻。结论: ERK1/2抑制剂PD98059能够减轻内毒素DIC时的多器官损伤,其机制与ERK1/2信号通路的抑制有关。

关键词: 细胞外信号调节激酶1/2, 脂多糖, 弥散性血管内凝血

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

中图分类号:

R965.2

朱海龙, 张根葆, 李伟, 张翠. 细胞外信号调节激酶1/2抑制剂PD98059对弥散性血管内凝血大鼠多器官损伤的保护作用[J]. 中国临床药理学与治疗学, 2012, 17(2): 159-163.

ZHU Hai-long, ZHANG Gen-bao, LI Wei, ZHANG Cui. Protective effects of ERK1/2 inhibitor PD98059 on multiple organ dysfunction in disseminated- intravascular-coagulation rat[J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2012, 17(2): 159-163.

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