局部植入利福平(RFP)缓释剂对P糖蛋白(P-gp)活性及激素性股骨头坏死的影响  

Effects of local sustained-release rifampicin (RFP) implantation on P-glycoprotein (P-gp) activity and steroid-induced osteonecrosis of femoral head

作　　者：费腾[1] 李朔[1] 潘建峰[1] 刘嘉[1] 陈晨[1] 郭常安[1] 邵云潮[1] 阎作勤[1] 

机构地区：[1]复旦大学附属中山医院骨科,上海200032

出　　处：《复旦学报（医学版）》2014年第5期575-580,588,共7页Fudan University Journal of Medical Sciences

基　　金：国家自然科学基金(81371966;81171671)~~

摘　　要：目的观察局部植入利福平(rifampicin,RFP)缓释剂对P糖蛋白(P-glycoprotein,P-gp)活性及激素性股骨头坏死的影响。方法建立激素性股骨头坏死的动物模型,取32只成年雌性兔,随机平均分为4组:3个对照组(空白/口服给药/肌肉注射)和局部缓释组(试验组)。其中局部缓释组于左侧股骨上段植入RFP缓释剂,右侧相同位置植入空白颗粒作为对照。4周后检测外周血、骨髓内单核细胞P-gp活性,肝内细胞色素P450(cytochrom P450,CYP450)含量,比较骨代谢血清学指标、组织学形态(HE、Masson染色)、股骨头坏死率。结果局部缓释组左侧骨髓内P-gp活性高于右侧(P<0.05)。口服、肌注组外周血P-gp活性和肝细胞色素P4503A含量高于局部缓释组(P<0.05)。HE染色示:局部缓释组左侧股骨头比右侧骨小梁增宽,脂肪细胞减少,骨坏死率降低(P<0.05);口服、肌注组股骨头骨质流失及脂肪化受到抑制。Massons染色示:口服、肌注及局部缓释组左侧股骨头骨质成熟胶原较多,矿化完全。结论局部植入RFP对外周P-gp及肝内CYP450无明显影响,可增强骨内P-gp活性,降低激素性骨坏死发生率。Objective To study the effects of local implantation of sustained-release rifampicin （RFP） on P- glyeoprotein （P-gp） activity and steroid-induced osteonecrosis of femoral head. Methods The animal model for steriod-induced oseteonecrosis of femoral head was established using 32 femal rabbits, which were equally divided into 4 groups：3 control groups （blank/oral/intramuscular injection group） and locally sustained release group （experimental group）. Experimental group were treated with RFP implantation in femoral head （left side only） ,meanwhile blank particle was implanted on the right side. Activity of peripheral and bone marrow P-gp, content of hepatic cytoehrom P450 （CYP450） were observed 4 weeks later,as well as serological indicators on osteogenic and osteoclastic activity. Histological result and osteoneerosis rate were analyzed from HE staining and Masson staining of femoral head. Results In experimental group,activity of bone marrow P-gp in the left femoral head was significantly increased compared with the right side （P〈0. 05）. Peripheral P-gp activity and the content of hepatic CYP450 were more up-regulated in both oral and intramuscular injection groups than that in the expenimental group （P〈0.05）. According to HE staining,the left femoral head had/showed wider bone trabecula, less fat cells and lower osteonecrosis rate compared with the right side in experimental group, and the deossification and pimelosis of femoral head were suppressed in oral and intramuscular injection groups. According to Masson staining, the left femoral head had more mature bone and was totally mineralization compared with the right side in oral, intramuscular injection and experimental groups. Conclusions I.ocal implantation of RFP increased P-gp activity in femoral head,but had no significant effect on peripheral P-gp or hepatic CYP4503A,and incidence of steroid-induced oseteonecrosis of femoral head was inhibited.

关 键 词：激素性股骨头坏死 P糖蛋白(P-gp) 细胞色素P450(CYP450) 利福平(RFP) 

分 类 号：R681.8[医药卫生—骨科学]