乌司他丁对急性肾脏创伤大鼠MMP-2/TIMP-2和NF-κB的调控作用  

Regulatory effect of ulinastatin on NF-κB and MMP-2/TIMP-2 in rats with acute renal trauma

作　　者：刘长海[1,2] 孙少华[3] 李海玲[4] 张伟华 

机构地区：[1]兰州大学基础医学院,兰州730000 [2]内蒙古医学院法医学系,呼和浩特010059 [3]兰州大学第一医院病理研究所,兰州730000 [4]内蒙古医学院预防医学系,呼和浩特010059 [5]赤峰市阿旗公安局,赤峰025571

出　　处：《第二军医大学学报》2008年第10期1188-1192,共5页Academic Journal of Second Military Medical University

摘　　要：目的:观察大鼠急性肾脏创伤中MMP-2、TIMP-2和NF-κB的表达,探讨乌司他丁对三者表达的影响和对创伤肾脏的保护机制。方法:用自由落体生物撞击仪撞击大鼠脊肋区,复制创伤动物模型:将66只清洁级Wistar大鼠随机分为3组:对照组(C)6只、单纯创伤组(TRA)30只、创伤后注射乌司他丁组(UTI)30只。根据创伤后时间的不同将后两组分别分为5个时相点(1、6、12、18、24h),每个时相点6只大鼠。联合应用组织芯片和免疫组织化学法检测各组肾脏中MMP-2/TIMP-2和NF-κB的表达。结果:TRA组:MMP-2、NF-κB在创伤后1h开始表达且显著高于对照组(P<0.05,P<0.01),两者分别在12、6h表达最强,以后逐渐下降;UTI组:MMP-2、NF-κB分别在18、12h表达最强且高于对照组(P<0.01),但已明显低于TRA组同期的表达(P<0.01,P<0.05);TIMP-2在该组的表达显著增强,于创伤后6、12、18h明显高于对照组和TRA组(P<0.01,P<0.05)。结论:肾创伤后NF-κB、MMP-2在肾组织中的表达增强,但TIMP-2表达升高不明显;乌司他丁能够通过抑制NF-κB、MMP-2在肾组织中表达和调节MMP-2/TIMP-2的平衡发挥肾保护作用。Objective： To investigate the expression of nuclear factor-κB（NF-κB）, matrix metalloproteinase-2 （MMP-2）, tissue inhibitor of metalloproteinase-2（TIMP-2） in the kidneys of rats with acute renal trauma,and to discuss the influence of ulinastatin on their expression and its protective mechanism on the kidney. Methods.. The animal model was established by striking the rachi-costaz zone with falling object from the height of 45 em. Sixty-six rats were randomly divided into three groups ： normal control group （C, n = 6 ）, trauma group （TRA, n = 30）, and ulinastatin＋ trauma （ UTI, n = 30）, the last 2 groups were further divided into 1 h, 6 h, 12 h, 18 h and 24 h subgroups, with 6 animals at each time point. Tissue microarray and immunohistochemistry were used to examine the expression of NF-κB and MMP2/TIMP-2 in different groups. Results： MMP-2 and NF-κB began to express 1 h after trauma in TRA group and their expression was significantly stronger than that in the controlgroup（P〈0. 05,P〈0. 01）,their expression reached the peaks at 12 h and 6 h after trauma and then gradually decreased. The expression of MMP-2 and NF-κB in UTI group reached their peaks 18 h and 12 h after trauma,respectively,and was significantly higher than that in the control group（P〈0.01）, but was lower than that in the TRA group at corresponding time points（P〈0.01 ,P〈0.05）. The expression of TIMP-2 was significantly stronger than that in the control group and TRA group at 6 h, 12 h and 18 h after trauma（P〈0.01, P〈0.05）. Conclusion： The expression of NF-κB, MMP-2 is increased in acute traumatic tissue of the kidney; the increase of TIMP-2 is not evident. Ulinastatin can protect the kidney by inhibiting the expression of MMP-2 and NF-κB and maintaining the balance of MMP-2/TIMP-2.

关 键 词：乌司他丁 组织芯片 创伤/损伤 NF—κB TIMP-2 MMP-2 

分 类 号：R641[医药卫生—外科学]