The Role Of Fibrinolytic System And Costimulatory Molecules In The Pathogenesis Of Inflammatory Myopathy

Objective:1. To develop a modified model for human idiopathic polymyosits(IPM).2. To explore the influence of fibrinolytic system intervention on IPM.Methods1. EAM induction by purified rabbit myosin:guinea pigs were divided randomly into two groups:control group (n=10) were inmunized by PBS and complete Freund adjuvant (CFA) for six times;EAM group (n=10) were immunized by purified rabbit myosin and CFA by the same protocol.Clinical manifestations and histological changes were observed.2. The role of defibrase in EAM:guinea pigs were divided randomly into three groups:control group (n=5);EAM group (n=12),after EAM induction,received injection of saline;defibrase group (n=15),after EAM induction, received injection of defibrase.Plasma levels of fibrinogen (FIB) and creatine kinase (CK) were detected.Clinical manifestation and histological changes were observed. The expressions of urokinase plasminogen activator (uPA) and matrix metalloproteinase 9 (MMP-9) in the muscles were examined immunohistochemically.3. The role of EACA in EAM:guinea pigs were divided randomly into three groups:EAM group (n=5),after EAM induction,received injection of saline;defibrase group (n=7),after EAM induction, received injection of defibrase;EACA group (n=7),after EAM induction, received injection of EACA.The expressions of uPA and MMP-9 in the muscles were examined immunohistochemically.Results:1. The clinical and histological score of EAM group were 1.40±0.74 and 1.70±1.06 respectively.The EAM inflammatory lesions were mainly mild to moderate.2. The clinical score of control,EAM and defibrase group were 0,1.38±0.68 and 1.57±0.7 respectively.The histological score were 0,1.88±1.32 and 2.80±1.15 respectively.The inflammation was more severe in defibrase group than in EAM group(P<0.05).There was no significant difference in FIB levels (P> 0.05).The expressions of uPA and MMP-9 were absent on normal muscular fibers but weak on small vessels.In EAM and defibrase group,strong expressions of upa and MMP-9 co-localized on degenerative/necrotic fibers,non-necrotic fibers surrounded by mononuclear cells,inflammatory cells and endothelial cells of arterioles and venules. The expressions of these two antigens were particularly stronger in defibrase group than in EAM group.3. The clinical score of EAM,defibrase and EACA group were 1.1±0.4,1.36±0.48 and 0.93±0.54 respectively.The histological score were 2.2±1.1,2.86±1.22 and 1.29±0.95 respectively.Inflammation in EACA group was more mild than in defibrase group(P<0.05).The expressions of uPA and MMP-9 were in accordance with the histological results,which was the least in EACA group.Conclusions:1. Developed more ideal animal model for human IPM.2. Defibrase probably activated uPA,further promoted MMP-9 to degrade ECM, which facilitated migration of inflammatory cells and exacerbated inflammation and necrosis of fibers in the end.3. By means of elevation of FIB,IPM could probably be treatable. Key words:idiopathic polymyositis,experimental autoimmune myositis, fibrinogen,defibrase,epsilon aminocaproic acid,urokinase plasminogen activator, matrix metalloproteinase 9 Objective:To analyse the expressions of CD28,CD152,CD80,CD86, CD40 and CD154,CD4 and CD8 on peripheral blood lymphocytes of patients with idiopathic polymyositis (IPM) and necrotizing myopathy (NM), further to study the relationship between these costimulatory molecules and inflammatory myopathy.Methods:Subjects were divided into three groups,healthy control group (HC) (n=5),IPM group(n=8) and NM group (n=9). Clinical data were collected. Muscular biopsies were carried out on the patients with IPM and NM. The expressions of CD4+,CD8+,CD4+CD28+,CD8+CD28+,CD152,CD80,CD86, CD40 and CD4+CD154+ on peripheral blood lymphocytes were detected by flow cytometry (FCM).The expressions of CD4+CD28- and CD8+CD28- were calculated.Results:1. Compared with HC group,the expression of CD4+and the percentage of CD4+CD28+/CD4 in IPM group decreased significantly (P<0.05),while the expressions of CD4+CD28- and CD 152 increased significantly(P<0.05).The percentage of CD4+CD28+/CD4+in NM group decreased significantly (P<0.05),while the expression of CD4+CD28- increased significantly (P<0.05) and CD 152 also showed ascending trend.2. There was no difference in the expression of CD80.Compared with HC group,the expression of CD86 in IPM and NM group both increased significantly (P<0.05).3. Compared with HC group,the expressions of CD40 increased significantly in IPM group (P<0.05).In NM group,the expression of CD40 also showed ascending trend and CD4+CD154+ increased significantly (P<0.05).Conclusions:The expressions of CD4+ and CD4+CD28+/CD4+ decreased significantly and CD4+CD28-,CD152,CD86,CD40 and CD4+CD154+increased significantly in inflammatory myopathy.This indicates the role of costimulatory molecules in the pathogenesis of inflammatory myopathy.