盲肠结扎穿刺致脓毒性肺损伤大鼠血清MMP-9水平研究

The study on the level of MMP-9 in rat serum with acute septic lung injury through cecal ligation and puncture

目的观察盲肠结扎穿刺(CLP)手术致大鼠脓毒性急性肺损伤(ALI)血清基质金属蛋白酶9(MMP-9)、IL-1、IL-8和IL-10表达的变化,探讨MMP-9在ALI形成及预后判断的作用机制。方法 50只SD大鼠随机分为假手术组(SHAM组)(n=8)和CLP手术组42只(6hn=8、12hn=8、24hn=10、48hn=16)。动物成模在各对应时间点取材,检测各组生存率、肺湿重系数、肺组织病理评分,以及MMP-9、IL-1、IL-8、IL-10血清水平。结果 MMP-9蛋白水平在CLP后24小时出现明显上升,显著高于对照组(P<0.01),48小时进一步升高(P<0.01);IL-1、IL-8、IL-10在CLP术后升高,48小时组均显著高于对照组(P<0.01);CLP术后大鼠明显肺损伤出现于24小时并持续加重,48小时组内大鼠均出现严重肺损伤;MMP-9与肺损伤病理程度存在正相关(r=0.704,P<0.01),相关性高于IL-1(P<0.01)、IL-8(P<0.01)和IL-10(P<0.05)。结论 CLP手术致大鼠脓毒性ALI血清MMP-9显著升高,MMP-9升高水平与肺损伤病理程度呈显著正相关,提示MMP-9可能在脓毒症后肺损伤的形成过程中扮演着关键性角色,对肺损伤的早期诊断和预后判断具有潜在价值。

Objective To investigate the serum levels of matrix metalloproteinase 9 （MMP-9）, IL-I,IL-8, and IL- l0 in rat with acute lung injury induced by sepsis by using method of cecal ligation and puncture. Methods 50 Rats were randomly divided into control group（n= 8）and CLP group （group6h n= 8, groupl2h n= 8, group24h n= 10, group48h n = 16）. Survival rate, lung wet weight index, pathology score of lung, MMP-9, IL-1, IL-8, and IL-10 serum levels were detected at every time point. Results MMP-9 serum levels in CLP group increased greatly after 24 hours, and higher than that in control group （P〈0.01） ; and further elevated at 48 hour compared with control group （P〈0.01）. IL-1, IL-8 and IL-10 increased after CLP, and elevated significantly at 48 hour. Pathological pulmonary injury was obviously at 24 hour after CLP. Additionally, pathological pulmonary injury was found in all samples at hours. MMP-9 serum levels were positively related with the level of pathological pulmonary injury. MMP-9 was more relevant with the level of patho- logical pulmonary injury than IL-1, IL-8（P〈0.01）, IL-8（P^0.01）, and IL-10（P^0.05）. Conclusion MMP-9 serum levels were found positively related with the level of pathological pulmonary injury which suggesting that MMP-9 may play a critical role in the process of acute lung injury induced by sepsis. Furthermore, MMP-9 serum levels may be a po- tential probe to early diagnosis and prognosis of lung injury.