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The Expression and Significance of Lysosomal Cathepsin B on the Coxsackievirus B1-Induced Polymyositis Model in the Guinea Pigs

Author: NiLiYan
Tutor: WangQiang
School: Fudan University
Course: Dermatology and Venereology
Keywords: Polymyositis Cathepsin B Apoptosis
CLC: R746.5
Type: Master's thesis
Year: 2011
Downloads: 20
Quote: 0
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Abstract


Background: polymyositis (polymyositis PM), etiology and pathogenesis is not clear. Currently considered to be induced by environmental factors (viruses, ultraviolet, etc.) by the cellular immune-mediated, in the background of a particular genetic susceptibility and disease. Have been reported in the literature lysosomal cathepsin B (Cathepsin B, CB)-mediated inflammation and apoptosis, and plays an important role in the proteolytic processing of amyotrophic, at home and abroad has not been CB involved in the pathogenesis of PM reports. Purpose: This study by detecting PM Coxsackie virus (Coxsackievirus B1, CVB1), virus-induced animal models of skeletal muscle fibers CB, CD8 T cells with the expression level of the muscle cell apoptosis, with the the CB specific inhibitor CA-074 Me intervention PM CB, and to explore the impact of CA-074 Me CB to clarify the mechanism of the protective effect of the muscle fibers, which provide a theoretical basis for clinical treatment of PM and its treatment. : Weight 158 ??± 20g 40 healthy female short-haired British species of guinea pigs were randomly divided into normal group (n = 8, D), the PM model group (n = 8, C group), sham intervention group (n = 8, E group), positive control group (n = 8, B) and CA-074 Me intervention group (n = 8, F group). Using CVB1 infection and rabbit muscle homogenate complete Freund's adjuvants repeated the immunologically normal guinea pigs PM induced to prepare CVB1, model. The positive control group be established in animal models of PM IFN-gamma intraperitoneal injection for 4 weeks; CA-074 Me intervention group in next day of CVB1 infection from the intraperitoneal injection of 1 week, the sham intervention group intraperitoneal injection of normal saline at the same point in time . Corresponding time points animals were sacrificed blood specimens to detect changes in muscle enzymes; take muscle tissue pathology observed; CD8 T cells were detected by immunohistochemistry, the CB expression level; situ end labeling (TUNEL) method to detect the guinea pig bone changes in muscle cell apoptosis. Results: (1) model the success rate of 40.2%, the PM model guinea pigs typical clinical symptoms, muscle enzymes abnormally elevated, multifocal myositis pathological changes. Muscle enzymes of the experimental group were higher than normal group (P lt; 0.05); B group F group of muscle enzymes showed a low level of increase, compared with the E group was statistically significant (P lt; 0.05). (2) normal group can be detected very few apoptotic myocytes; apoptotic index of the experimental group were higher than the D group, and there is a significant difference; F apoptotic index is lower than the E group (P lt; 0.05); therewith In contrast, group B respectively in Group E, F apoptotic index were significantly different (P lt; 0.05) (3) normal group has a small amount of CD8 CB Expression In contrast, the experimental group were increased expression; CD8 and CB expression of the F group were significantly lower than the E group (P lt; 0.05); group B and group E F group CB expression were significant differences (P lt; 0.05). Conclusions: (1) CB exists in the PM guinea pig model of high expression mediated inflammation and apoptosis may play an important role in the pathogenesis of the PM. (2) PM guinea pig model of myocardial apoptosis; muscle tissue expression raised the CB may initiate and participate in muscle cell apoptosis, is of great significance to the pathogenesis of PM. (3) CA-074 Me can reduce its mediated inflammation and apoptosis by inhibiting the over-expression of the CB, and thus play a protective effect of PM guinea pig model of muscle tissue. (4) INF-gamma may promote inflammation and induce apoptosis involved in the occurrence and development of the PM model in guinea pigs.

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