The Research Of The Effect Of NF-κB Inhibitor Pyrrolidine Dithiocarbamate(PDTC) To Aseptic Loosening That Induced By Wear Debris Of High Molecular Weight Polyethylene Around Prosthesis

Objective:To observe the effect of NF-κB inhibitor pyrrolidine dithiocarbamate (PDTC) to TNF-αand osteoclasts that induced by wear debris of high molecular weight polyethylene(UHMWPE) around prosthesis, To observe the mechanism of action of NF-κB inhibitor, to search a promising therapeutic candidate for the prevention and treatment of aseptic loosening.Methods:One experiment: We utilized the air-pouch model in Kunming mice. Twenty-four mice were used, eight per group.The positive control group(A1) and the experimental group(A2) were pumped in air-pouch with suspension of UHMWPE debris, The negative control group(A3) was pumped in air-pouch with normal sodium. The positive control group(A1) was treated intraperitoneal injection with normal sodium;The experimental group(A2) and the negative control group(A3) was treated intraperitoneal injection with PDTC; The mice were sacrificed after 7 days.The contents of TNF-αwas detected by ELISA.Other experiment: We utilized the murine calvaria osteolysis model in Kunming mice. Twenty-four mice were used, eight per group.The positive control group(B1) was treated intraperitoneal injection with normal sodium;The experimental group(B2) was treated intraperitoneal injection with PDTC;The negative control group(B3) was treated intraperitoneal injection with PDTC.The mice were sacrificed after 14 days.The quantity of osteoclast was measured by TRAP specific stain of immunohistochemistry.Result:The contents of TNF-αof A1,A2,A3 was 6.3429±0.7475(OD/g),5.0428±0.8105(OD/g),3.5010±0.7248(OD/g) respectively; The quantity of osteoclast showed that B1,B2,B3 was 12.8500±3.5484,7.2000±2.6897and 3.7250±1.4617 respectively. The differences of each group comparison(A1:A2;A1:A3;A2:A3 and B1:B2;B1:B2;B2:B3) have statistical significance(P<0.05 or P<0.01).Conclusion:this study provides the evidence that PDTC had inhibited the generation of TNF-αAND osteoclasts induced by wear debris of UHMWPE in the tissue around implants. It represents a promising therapeutic candidate for the prevention and treatment of aseptic loosening.