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、28 d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 .
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