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(P<0.01),乌司他丁组SOD明显高于百草枯组(P<0.05)。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(P<0.01),乌司他丁组各指标明显低于百草枯组(P<0.05)。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(P<0.01),乌司他丁组各指标明显低于百草枯组(P<0.05)。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(P<0.01),乌司他丁组MMP-2明显低于百草枯组(P<0.05)。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。
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 , pa-raquat 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 treat-ment.The serum levels of MDA, SOD, IL-6, IL-10 and TNF-αwere measured after 1 d, 3 d, 7 d, 14 d, 21 d and 28 d. The expression levels of p 38 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-αin 1 d, 3 d and 7 d in paraquat group and ulinastatin group increased compared with con-trol 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 in-hibiting p38 MAPK signaling pathway and ameliorating inflammatory and oxidative responses .
出处
《中国病理生理杂志》
CAS
CSCD
北大核心
2015年第1期166-171,共6页
Chinese Journal of Pathophysiology
基金
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(No.2012YA1217)
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
KEY WORDS] Ulinastatin
Acute lung injury
Paraquat
Mitogen-activated protein kinases
Tissue inhibitor of metalloproteinases
Matrix metalloproteinases