Toll样受体4特异性抑制剂TAK242对假体周围骨溶解的研究  

Effect of toll like receptor 4 specific inhibitor TAK242 on periprosthetic osteolysis

作　　者：牛竣槭 毕方刚[1] 郭子博 李云龙[1] 田科[1] Niu Junqi;Bi Fanggang;Guo Zibo;Li Yunlong;Tian Ke(Department of Orthopedics,the First Affiliated Hospital of Zhengzhou University,Zhengzhou 450052,China)

机构地区：[1]郑州大学第一附属医院骨科,郑州450052

出　　处：《中华实验外科杂志》2023年第7期1258-1261,共4页Chinese Journal of Experimental Surgery

基　　金：2022年河南省高等学校重点科研项目(22A320014)

摘　　要：目的探讨Toll样受体4(TLR4)特异性抑制剂瑞沙托维(TAK242)对假体周围骨溶解的疗效机制。方法将12只健康成年雄性无特定病原体(SPF)级SD大鼠采用简单随机分组法分成3组,空白组,模型组,TAK242实验组,每组4只。空白组不放置聚乙烯颗粒(PE),模型组,实验组均放置聚乙烯颗粒。空白组、模型组术后7d给予生理盐水腹腔注射。实验组手术7d开始腹腔注射TAK242(药物浓度为2.5mg/ml),剂量5mg/kg,两天1次,共2个月。随后处死动物提取血清,用酶联免疫吸附试验(ELISA)检测各组骨保护蛋白(OPG),核因子-κB受体活化因子配体(RANKL),并分析OPG/RANKL趋势。用Micro-CT分析假体周围骨质情况,并用苏木精-伊红(HE)染色法和抗酒石酸酸性磷酸酶(TRAP)染色,分析破骨细胞数量。多样本均数的两两比较采用单因素方差分析。结果ELISA示,TAK242组OPG、OPG/RANKL高于模型组[(557.26±32.74)pg/ml、(19.87±1.58)%比(421.95±14.06)pg/ml、(13.18±0.68)%,F=43.27,P<0.01、F=45.36,P<0.01]。TAK242组RANKL低于模型组[(28.10±1.16)pg/ml比(32.08±1.67)pg/ml,F=11.45,P<0.05]。Micro-CT示,TAK242组BMD、BV/TV、Tb.N高于模型组[(20.71±2.22)g/cm^(2)、(7.69±0.85)%(0.78±0.09)1/mm比(13.73±0.54)g/cm^(2),(5.02±0.18)%、(0.53±0.07)1/mm,F=37.14,P<0.01、F=37.84,P<0.01、F=17.94,P<0.01]。TAK242组Tb.Pf低于模型组[(13.63±1.66)1/mm比(17.07±1.53)1/mm,F=9.29,P<0.05]。TAK242实验组HE染色较模型组比,骨小梁数量、厚度增高,磨损颗粒诱导的骨质吸收区域变小,炎性浸润较对照组减少。TAK242实验组TRAP染色较模型组比少量破骨细胞浸润,炎性细胞浸润少。结论TLR4特异性抑制剂TAK242有效抑制假体周围骨溶解。Objective To explore the therapeutic mechanism of toll like receptor 4(TLR4)specif-ic inhibitor TAK242 on periprosthetic osteolysis.Methods A total of 12 healthy adult male pathogen free(SPF)grade SD rats were randomly divided into three groups:blank group,model group,and TAK242 ex-perimental group,with 4 rats in each group.The blank group were not given polyethylene particles(PE),and the model group and experimental group were given polyethylene particles.The blank group and model group were given saline intraperitoneal injection 7 days after surgery.The experimental group received in-traperitoneal injection of TAK242(2.5 mg/ml)starting 7 days after surgery,with a dose of 5 mg/kg,once every two days,for a total of 2 months.Subsequently,the animals were euthanized and serum was extrac-ted.Enzyme linked immunosorbent assay(ELISA)was used to detect osteoprotegerin(OPG)and receptor activator of nuclear factor-kB ligand(RANKL)and analyze OPG/RANKL trends.Micro CT was used to analyze the bone around the prosthesis,and hematoxylin eosin(HE)staining and tartrate resistant acid phosphatase(TRAP)staining were used to analyze the number of osteoclasts.Results The ELISA showed the OPG/RANKL(19.87±1.58)in the TAK242 experimental group was significantly higher than that in the model group(13.18±0.68,F=45.36.P<0.01).The Micro-CT data showed the bone density(BMD),bone volume fraction(BV/TV),and trabecular bone number(Tb.N)in the TAK242 experimen-tal group(20.71±2.22,7.69±0.85,0.78±0.09)were significantly increased compared to the model group(13.73±0.54,5.02±0.18,0.53±0.07,F=37.14,P<0.01;F=37.84,P<0.01;F=17.94,P<0.01).The bone trabecular pattern factor(Tb.Pf)in the TAK242 experimental group(13.63±1.66)was significantly reduced compared to the model group(17.07±1.53,F=9.29,P<0.05).There was no statistically significant difference in the trabecular separation(Tb.SP)between the TAK242 group(0.59±0.09)and the model group(0.59±0.07,F=0.001,P>0.05).The HE staining of the TAK242 experimental group showed an increase in the

关 键 词：TOLL样受体4 TAK242 假体周围骨溶解 聚乙烯 

分 类 号：R68[医药卫生—骨科学]