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乌司他丁保护百草枯中毒大鼠肺免受损伤的作用
引用本文:陈达,张洪颖,贾浩,朱杰.乌司他丁保护百草枯中毒大鼠肺免受损伤的作用[J].中国病理生理杂志,2015,31(1):166-171.
作者姓名:陈达  张洪颖  贾浩  朱杰
作者单位:中国医科大学附属第四医院急诊科, 辽宁 沈阳 110032
基金项目:辽宁省自然科学基金资助项目( No.2013021059);中国医科大学附属第四医院青年创新发展计划
摘    要:目的:探讨乌司他丁保护百草枯中毒大鼠肺免受损伤的作用及其机制。方法:Wistar大鼠108只,随机分为对照组、百草枯组和乌司他丁组。百草枯组和乌司他丁组给予百草枯灌胃染毒,对照组给予无菌生理盐水灌胃,乌司他丁组同时给予乌司他丁治疗。1、3、7、14、21、28 d测血清中的MDA、SOD、IL-6、IL-10和TNF-α水平,以及肺组织中的p38 MAPK、MMP-2和TIMP-1表达水平。结果:1、3、7 d百草枯组和乌司他丁组的SOD均较对照组下降(P0.01),乌司他丁组SOD明显高于百草枯组(P0.05)。1、3、7 d百草枯组和乌司他丁组的MDA、IL-6、IL-10及TNF-α均较对照组增高(P0.01),乌司他丁组各指标明显低于百草枯组(P0.05)。1、3、7、14、21、28d百草枯组和乌司他丁组肺组织中的p38 MAPK及TIMP-1均较对照组增高(P0.01),乌司他丁组各指标明显低于百草枯组(P0.05)。1、3、7、14、21 d百草枯组和乌司他丁组肺组织中的MMP-2均较对照组增高(P0.01),乌司他丁组MMP-2明显低于百草枯组(P0.05)。结论:乌司他丁通过抑制p38 MAPK信号通路及抗炎、抗氧化作用保护百草枯中毒大鼠肺免受损伤的作用。

关 键 词:乌司他丁  急性肺损伤  百草枯  丝裂原活化蛋白激酶  金属蛋白酶组织抑制物  基质金属蛋白酶  
收稿时间:2014-08-20

Ulinastatin protects rat pulmonary tissues from paraquat-induced acute injury
CHEN Da,ZHANG Hong-ying,JIA Hao,ZHU Jie.Ulinastatin protects rat pulmonary tissues from paraquat-induced acute injury[J].Chinese Journal of Pathophysiology,2015,31(1):166-171.
Authors:CHEN Da  ZHANG Hong-ying  JIA Hao  ZHU Jie
Institution:Department of Emergency, The Fourth Affiliated Hospital, China Medical University, Shenyang 110032, China
Abstract:AIM: To investigate the protective effects of ulinastatin on the rats with paraquat-induced acute lung injury and its mechanisms. METHODS: The Wistar rats (n=108) were randomly divided into control group, paraquat group and ulinastatin group. The rats in paraquat group and ulinastatin group were given paraquat by gavage, while the rats in control group were given sterile saline by gavage. The rats in ulinastatin group were also given ulinastatin treatment. The serum levels of MDA, SOD, IL-6, IL-10 and TNF-α were measured after 1 d, 3 d, 7 d, 14 d, 21 d and 28 d. The expression levels of p38 MAPK, MMP-2 and TIMP-1 in the lung were also measured. RESULTS: The levels of SOD in 1 d, 3 d and 7 d in paraquat group and ulinastatin group were significantly lower than those in control group (P<0.01). The level of SOD in ulinastatin group was significantly higher than that in paraquat group (P<0.05). The levels of MDA, IL-6, IL-10 and TNF-α in 1 d, 3 d and 7 d in paraquat group and ulinastatin group increased compared with control group (P<0.01), and those in ulinastatin group were significantly lower than those in paraquat group (P<0.05). The levels of p38 MAPK and TIMP-1 in 1 d, 3 d, 7 d, 14 d, 21 d and 28 d in paraquat group and ulinastatin group were higher than those in control group (P<0.01), and those in ulinastatin group was significantly lower than those in paraquat group (P<0.05). The level of MMP-2 in 1 d, 3 d, 7 d, 14 d and 21 d in paraquat group and ulinastatin group increased compared with control group (P<0.01), and that in ulinastatin group was significantly lower than that in paraquat group (P<0.05).CONCLUSION: Ulinastatin protects the lung tissues of rats from paraquat-induced acute lung injury by inhibiting p38 MAPK signaling pathway and ameliorating inflammatory and oxidative responses.
Keywords:KEY WORDS] Ulinastatin  Acute lung injury  Paraquat  Mitogen-activated protein kinases  Tissue inhibitor of metalloproteinases  Matrix metalloproteinases
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