Preliminary Study Of The Effect And Mechanism Of Photodynamic Therapy On Animal Model Of Rheumatoid Arthritis

Aneumatoid arthis (RA) is a common chronic autoimmune disease Thepathology of RA is characterized by a proliferative synovitis, which behavessimilar to localized neoplasm, and destroying articular cartilage and bone TheSuperproliferative synoviocytes play a pivotal role in leading to damage ofarticular cartilage and bone Attempts to destroy proliferative synovium willbe help to patient with RA Photodynamic therapy (PDT) has been used totreat various oncologic diseases It principle is that interaction of theexcited-state photosensitizer with molecular oxygen in the target tissuegenerates short-lived, reactive oxygen species (ROS) that cause lipid andamino acid peroxidation, resulting in the disruption of celImembrane-associated and intracellular function The inflamed synovium ofRA exhlbits many of the characteristics of neoplastic tissue and theorcticallymay be well suited for PDT It has been show that the cuitured synovial cell ofRA could rapidly uptake hematoporphyrin monomethl ether (HMME) and thecytotoxic effect was strong after the HMME-mediated PDT in our laboratoryIn the present study, the uptake characteristics of HMME of the inflamedsynovium and other tissue were investigated with optical multichannelanalyzer (OMA), and the effect and mechanism of transdermal PDT on animalmodel of RA were investigatqdMethods:l. TyPe II collagen induced arthritis (CIA)ln the rat ank1e joint andoVathumin as antigen induced arthritis WA) in the rabbit knee joint wereestab1ish2 Qualitative evaluation of me in skin, muscle, synovium, cedilagearound joint and blood was performed by OMA3 The CIA rats were treated on day 7 after hind paw swelling and erythemaAnimals were injected intravenously with ase at a dose of 10mg/kg,tWenty minuots 1ater, one ankle of the rats random1y assigned was exPosedlaser irradiation at l00J/cm fOr l000 seconds, and another ankle wasM grouP wihout laser The other two groups is unmanipulatedcontrol group and untreated CIA group Bimaleolar ankle widthmeasuremellts were taken in all animals every tWo days using amicrometer The histopathology of the ank1e Joint was assessed at day 21after disease onset4 The pro1iferating cell nuclear antigen WCNA of CIA treated by PDT andthe HMME group without laser was doterdrined by immunohistochemiStry5 The AfA rabbits were treated on day 7 after knee swelling and erythemaThe theraPy invo1ved lntravenous injection of l0mg/kg HMME, fOl1owedby 20 minues period in dim light, and transdermal light treatment with\l00 J/cm2 fOr l000 seconds The inner sides of the treated Anees wereirradiated at first, and then the outer side did 24 hours later, the synovialtissue of the Anees joint were removed and in situ cel1 aPoptosis wasdetCCted With tednal deoxync1eotidyl transferase-mediated dUTP nickend labeling (TUNE)R6suIt8:l The pathologic changes of CIA and AIA include subsynovial inflammation,opovial hyPerplasia, pannus formation, cartilage and bone destructionresemble RA.2 The studies demonstrated that there are different uptake of HMME withinskin, muscle, synovium, cartilage and b1ood, and the synovium cou1draPidly uPtake more ase than skin and cartilage at the firSt 30 minuesaller intravenous injection of HMME3 The bimaleolar anke width had no different among PDT treated group,H group withollt 1aser and untreated CIA group But hlstologicalevaluation showed statiStical1y significallt reductions in synovialhyperplasia, pannus formation and cart1lage reosion, bone destruction andtotal score in PDT treated group4 Image analysis showed that the ratlo bforeen the areas of the coufltedobect (PCNA positive cells) to that of the entire area (PerArea) in PDTtreated grOup is lower than that in conirol group, but the integrated oPticaldensity (IOD) had no different between the two groups5 Imape analysis showed that the ratio between the area of the countedobject (aPoptosis positiVe cells) to that of the e...