目的 探讨尿激酶型纤溶酶原激活物（urokinase type plasmin-ogen activator，uPA）及其Ⅰ型抑制剂（plasminogen activator inhibitor,PAI-1）mRNA 在豚鼠实验性自身免疫性肌炎(experimental autoimmune myositis,EAM)肌肉中的表达及其意义。 方法 利用兔骨骼肌肌球蛋白加完全弗氏佐剂多次免疫豚鼠，同时联合腹腔注射百日咳毒素，制成EAM模型，观察其临床表现、血CK、肌肉病理的改变；用RT-PCR 方法检测11例EAM组模型成功豚鼠肌肉uPA 和PAI-1基因mRNA的表达，以10 例正常豚鼠的肌肉作为对照组。 结果 （1）EAM组肌肉中uPA、PAI-1基因mRNA的表达均较正常组显著增高（ P < 0.01) ；（2）肌肉中uPA与PAI-1基因mRNA表达的比例在正常组和EAM组无统计学差异( P <0.01)。 结论 uPA、PAI-1可能参与了EAM的发病机制。
Abstract
Objective To study the expression and significance of gene mRNA of urokinase type plasminogen activator and its inhibitor 1type(PAI-1)in the muscle of exprimental autoimmune myositis (EAM) guinea pigs. Methods The EAM model was established by repeatedly immunizating guinea pigs with rabbit skeletal muscle myosin plus Freund's complete adjuvant and giving these pigs a celiac injection of pertussis toxin. The changes in clinical symptoms, serum creatine kinase and pathology were observed. The expression level of uPA and PAI-1 in the skeletal muscle was detected by RT-PCR and compared between EAM group ( n =11) and normal group ( n =10). Results (1) The level of expression of the uPA and PAI-1 mRNA in the muscle increased significantly in EAM group, compared with normal group（ P <0.01). (2)There was no difference in the ratio between expression of the uPA and PAI-1 mRNA in the muscle tissues of EAM group and normal group ( P <0.01). Conclusions uPA and PAI-1 may contribute to the pathogenesis of EAM.
关键词
实验性自身免疫性肌炎 /
尿激酶型纤溶酶原激活物 /
纤溶酶原激活物抑制剂 /
豚鼠
Key words
exprimental autoimmune myositis /
urokinase type plasmin-ogen activator /
plasminogen activator inhibitor /
guinea pig
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参考文献
［1］ Castellino F J,Ploplis V A.Structure and function of the plasminogen/ plasmin system ［J］.Thromb Haemost,2005,93(4):647-654.
［2］ 张庆成，赵杰，汪承炜，等.CD 40L、MMPs和a-GMP-140在急性冠脉综合征致病中的作用［J］. 武警医学，2011,22(3):220-222.
［3］ Luikart S M， Masri D， Wahl, et al . Urokinase is required for the formation of mactinin, an alpha-actinin fragment that promotes monocyte/macrophage maturation［J］. Biochim Biophys Acta, 2002,1591(1-3):99-107.
［4］ Navaneetha K Rao, Guo Ping Shi, Harold A.Urokinase receptor is a multifunctional protein: influence of receptor occupancy on macrophage gene expression ［J］.J Clin Invest, 1995,96(1):465-474.
［5］ Paulis A, Montuori N, Prevete N, et al . Urokinase induces basophil chemotaxis through a urokinase receptor epitope that is an endogenous ligand for formyl peptide receptor-like 1 and -like 2 ［J］. J Immunol， 2004,173(9):5739-5748.
［6］ Suelves M, Vidal B, Serrano A L, et al . uPA deficiency exacerbates muscular dystrophy in MDX mice ［J］.J Cell Biol,2007,178(6): 1039 - 1051.
［7］ Lluis F J，Roma M， Suelves, et al . Urokinase dependent plasminogen activation is required for efficient skeletal muscle regeneration in vivo ［J］.Blood, 2001,97(6):1703-1711.
［8］ Lòpez Alemany R， Suelve M，Muoz Cánoves P.Plasmin gener-ation dependent on α-enolase-type plasminogen receptor is required for myogenesis ［J］.Thromb Haemost,2003,90(4):724-733.
［9］ Koh T J, Bryer S C, Pucci A M, et al . Mice deficient in plasminogen activator inhibitor-1 have improved skeletal muscle regeneration ［J］.Am J Physiol Cell Physiol, 2005, 289(1): 217– 223.
［10］Czekay R P, Loskutoff D J. Plasminogen activator inhibitors regulate cell adhesion through a uPAR-dependent mechanism［J］. J Cell Physiol,2009,220(3):655-663.
［11］Zorio E, Gilabert-Estellés J, Espa a F, et al . Fibrinolysis: the key to new pathogenetic mechanisms ［J］.Curr Med Chem，2008, 15(9): 923-929.
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