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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
刘长海1,2,孙少华3*,李海玲4,张伟华5
0
(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)
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、24 h),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1 h开始表达且显著高于对照组(P<0.05,P<0.01),两者分别在12、6 h表达最强,以后逐渐下降;UTI组:MMP-2、NF-κB分别在18、12 h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、18 h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。
关键词:  乌司他丁  组织芯片  创伤/损伤  NF-κB  TIMP-2  MMP-2
DOI:10.3724/SP.J.1008.2008.01188
投稿时间:2007-11-03修订日期:2008-03-07
基金项目:
Regulatory effect of ulinastatin on NF-κB and MMP-2/TIMP-2 in rats with acute renal trauma
LIU Chang-hai1,2,SUN Shao-hua3*,LI Hai-ling4,ZHANG Wei-hua5
(1.Preclinical Medical College,Lanzhou University,Lanzhou 73000,China*2.Department of Forensic Medicine,Inner Mongolian Medicine College,Hohhot 010059*3.Pathological Institute,the First Hospital of Lanzhou University,Lanzhou 730000*4.Department of Preventive Medicine,Inner Mongolian Medicine College,Hohhot 010059*5.Aqi Public Security Bureau of Chifeng City,Chifeng 025571)
Abstract:
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 cm.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 control group(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
Key words:  ulinastatin  tissue microarry  trauma/injuries  nuclear factor-κB  tissue inhibitor of metalloproteinase-2