| Backgroud:The underlying etiology and pathogenesis of polymyositis(PM) remain elusive. It is currently considered that the pathology of PM is a kind of thymus derived cell mediated myopathies. PM is triggered by environmental factors in genetically susceptible individuals. Studies have demonstrated that Cathepsin B (Cathepsin B, CB) can mediate the occurrence of inflammation and apoptosis. Cathepsin B also plays an important role in the proteolysis process of the muscle atrophy. However, few studies indicate the correlation between CB and the pathogenesis of PM.Objective:Through examining cell apoptosis and the expression of CB and CD8+T cell in the skeletal muscle of guinea pigs with the coxsackievirus B1-induced polymyositis, we investigate the role of CB in the pathogenesis of PM, the correlation between CB and CD8+T cell and apoptosis in the skeletal muscle. We study the influence of the inhibitor CA-074 Me on CB and its protection on muscle fiber in order to provide scientifical theoretical basis and ideas for clinical treatment of PM.Methods:40 healthy female shorthair guinea pigs weighing 158±20g were randomly divided into five groups:normal group(D group), positive control group(B group),PM model group(C group),group without intervention(E group) and intervention group(CA-074 Me, F group). The animal model of PM was induced by repeatedly immunizing shorthair guinea pigs with muscle homogenates of rabbit infected coxsackievirus B1 added to complete Freund's adjuvant (CFA). At the same time, the same volume of normal saline was treated in group D. From day 2 to day 8, CA-074 Me was given intraperitoneally per day in group F guinea pigs and same volume of normal saline for group E. Group B were given IFN-γintraperitoneally per day for 4 weeks. On week 5(C,D,E,F group) and week 8(B group) the serum was collected to detect serum muscle enzymes. Skeletal muscles were removed for histologic study;the expression of CD8 and CB were measured by the method of immunohistochemistry. The apoptosis of muscular tissue was detected by the method of terminal deoxynucleotidy transferase-mediated dUTP-biton nick end labeling(TUNEL).Results:(1)40.2% guinea pigs were induced PM showed typical manifestation of PM,the serum enzymes evidently elevated and the histopathological muscular changes of PM.The value of serum enzyme in the experimental groups was higher than that of normal group. Serum enzyme in the group F also increased,but on a low level, lower than group E(P<0.05).(2)TUNEL positive cells were hardly detected in the normal group. Compared with normal group,the apoptosis index(AI) of the experimental groups was higher (P<0.05). The apoptosis index of group F was lower than that of group E(P<0.05);in contrast to group F, AI of group B was higher than group E.(3)The result of immunohistochemistry suggested that a certain amount of positive cell counting of CD8 and CB was detected in the normal group. Compared with group D, the expression of CD8 and CB was evidently increased in the other group. The up-regulation of CD8 and CB took on a low level in the group F(P<0.05). And the positive cell counting of CB in the group B was remarkably less than in group F and group E(P<0.05).Conclusion:(1) Cathepsin B is over-expressed in the guinea pigs with polymyositis, which may contribute to the pathogenesis of polymyositis.(2) The apoptosis in skeletal muscle. Up-regulated CB in muscular tissue of PM may cause this phenomenon. If confirmed, the conclusion will lead to development of certain kind diseases.(3) CA-074 Me could attenuate the CB-mediated inflammatory response and cell apoptosis by suppressing excessive expressing of CB in muscular Tissue. In this way, CA-074 Me protects the skeletal mucle and plays pivotal role in curing the polymyositis in the shorthair guinea pigs. (4)IFN-γcould promote the inflammatory reaction and induce the apoptosis of muscle cell, which might be involved in the pathogenesis and pathology of PM model in the guinea pigs.
|
PDF Full Text Request