A Study On The Immunopathological Changes Of The Skeletal Muscle Microvessels And Muscle Fibers And Their Pathogenesis In DM/PM

Objective: To study the expression of NCAM,CD105,COX-2 and NF-κB(p65)in the skeletal muscle microvascular endothelial cells and muscle fibers of dermatomyositis (DM) / polymyositis (PM), the effect of the serum of the DM patients of NF-κB(p65)on HUVEC in vitro. We want to clarify the pathological changes of microvessels and the pathogenetic mechanism of muscle fiber damage in DM/PM to give new view for earlier diagnosis and pathogenesis.Methods: (1)We performed biopsy specimens from 25 patients with DM/PM, biopsy specimens were Paraffin-embedded,stained with hematoxylin&eosin;(2) The expression of NCAM,CD105,COX-2 and NF-κB(p65)was detected in the skeletal muscle of DM/PM with the immunohistochemistry;(3)the effect of the serum of the 16 pre-treatment and 6 post-treatment DM patients on the expression of NF-κB(p65)on HUVEC in vitro was examined with the immunocytochemistry.Result: (1) Hematoxylin&eosin staining showed that the pathological changes of muscle biopsy with DM were reduction of microvessels, perifascicular atrophy of muscle fibers, inflammatory infiltration around vessels. the pathological changes of muscle biopsy with PM were muscle fibers degeneration and inflammatory infiltration in perimysium; (2)The expression of NCAM was particularly prominent with a perifascicular pattern in DM and an intrafascicular pattern in PM. There was no expression in health controls; (3) The expression of CD105 was 20 positive out of 21 patients with DM, there was no expression in 4 patients with PM. There was significant difference between DM and PM (P<0.05);(4)COX-2 was expressed in muscular microvessels in DM/PM, COX-2 was positive correlation with CD105 and NF-κB ( p65 )( r=0.5068,P=0.0191 and r=0.5795,P=0.0024); (5) The higher expression of NF-κB(p65)in the skeletal muscle microvascular endothelial cells and muscle fibers of DM/PM than health controls(P <0.05).there was no expression in health controls; (6) To investigate the effect of the serum of the pre-treatment DM patients on the expression of NF-κB(p65)on HUVEC in vitro after 6 hours ,the nucleus express positive. which was (11.126±1.920)% , after 24 hours was (17.048±1.140)% ,which was more than 6 hours. There was significant difference (P<0.001). The effect of serum of the post-treatment group of the DM patients on the expression of NF-κB(p65)in HUVEC was lower expression at 6 hours and 24 hours than the effect of serum of the pre-treatment group of the DM patients on the expression of NF-κB(p65)in HUVEC at 6 hours and 24 hours.Conclusion: (1) muscle fibers degeneration and inflammatory infiltration showed that there was inflammatory damage in muscle of DM/PM patients. The reduction of microvessels in DM patients showed it was microvascular change. perifascicular atrophy suggested change was particularly prominent with a perifascicular pattern in DM; (2) The expression of NCAM suggested there were regenerating muscle fibers, regenerating cells were particularly prominent with a perifascicular pattern in DM and an intrafascicular pattern in PM, it may provide method for distinguishing DM and PM; (3) the expression of CD105 in skeletal muscle was positive in DM, but negtive in PM. It indicates there is angiogenesis in DM. But not in PM, it may provide method for distinguishing DM and PM. there was a positive correlation between the CD105 and COX-2 , which suggested that COX-2 participated in angiogenesis; (4) The expression of NF-κB(p65)in the skeletal muscle microvascular endothelial cells and muscle fibers, COX-2 was expressed in muscular microvessels in DM/PM, there was positive correlation between COX-2 and NF-κB(p65), These suggest that COX-2 and NF-κB(p65)may play an important role in pathological changes of microvessels and the pathogenetic mechanism of muscle fiber damage in DM/PM. (5) the serum of the pre-treatment DM patients could increase the expression of NF-κB(p65)in HUVEC in vitro,but the serum of the post-treatment DM patients could decrease the expression of NF-κB(p65)in HUVEC in vitro, It suggested that the serum of DM patients contained the components that could activate NF-κB(p65).