NF-κB抑制剂PDTC抑制UHMWPE磨损颗粒诱导界膜组织产生TNF-α的实验研究

Effect of NF-κB inhibitor pyrrolidine dithiocarbamate (PDTC) to TNF-αthat induced by wear debris of high molecular weight polyethylene(UHMWPE)in the tissue around implants

目的探讨NF-κB抑制剂PDTC对高分子量聚乙烯磨损颗粒(UHMWPE)诱导的假体周围界膜组织产生TNF-α的影响,寻找防治假体周围骨溶解的方法。方法用昆明小鼠24只构建air-pouch模型,随机分成两组,每组8只,阳性对照组(囊内注入UHMWPE颗粒悬液,腹腔注射生理盐水);实验组(囊内注入UHMWPE颗粒悬液,腹腔注射PDTC),阴性对照组(囊内注入生理盐水,腹腔注射PDTC)),7天后处死动物,ELISA法检测囊壁组织中TNF-α的含量。结果阳性对照组囊壁组织TNF-α含量为6.3429±0.7475(OD/克);实验组囊壁组织中TNF-α含量为5.0428±0.8105;阴性对照组囊壁中TNF-α含量为3.5010±0.7248。其中阳性对照组与实验组、阳性对照组与阴性对照组、实验组与阴性对照组之间两两对比均有显著统计学差异(<0.01)。结论NF-κB抑制剂PDTC能够抑制UHMWPE颗粒诱导的界膜组织中TNF-α的产生,对假体周围骨溶解有防治作用。

Objective To observe the effect of NF-κB inhibitor pyrrolidine dithiocarbamate （PDTC） to TNF-α that induced by wear debris of high molecular weight polyethylene （UHMWPE） in the tissue around implants, to search a promising therapeutic candidate for the prevention and treatment of aseptic loosening. Methods We utilized the air-pouch model in Kunming mice. Twenty-four mice were used, eight per group.The positive control group and the experimental group were pumped in air-pouch with suspension of UHMWPE debris, The negative control group was pumped in air-pouch with normal sodium. The positive control group was treated intraperitoneal injection with normal sodium; The experimental group and the negative control group was treated intraperitoneal injection with PDTC; The mice were sacrificed after 7 days.The contents of TNF-α was detected by ELISA. Result The contents of TNF-α of the positive control group was 6.3429±0.7475（OD/g）; The contents of TNF-α of the experimental group was 5.0428±0.8105（OD/g）; The contents of TNF-α of the negative control group was 3.5010±0.7248（OD/g）. There was a statistical significant difference in the positive control group and the experimental group （P〈0.01）,the positive control group and the negative control group （P〈0.01）, the experimental group and the negative control group （P〈0.01）. Conclusion this study provides the evidence that PDTC had inhibited the generation of TNF-α 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.