超声靶向万古霉素负载微泡对大鼠膝关节急性假体周围感染的治疗效果  

Efficacy of ultrasound-targeted vancomycin-loaded microbubbles in treating periprosthetic joint infection in rat knee joints

作　　者：姚粝芹 孙学斌[1] 郭子玉 马有财 李亦丞 杨建华[3] 曹力[2,4,5] 穆文博 YAO Liqin;SUN Xuebin;GUO Ziyu;MA Youcai;LI Yicheng;YANG Jianhua;CAO Li;MU Wenbo(Department of Sports Medicine,the First Affiliated Hospital of Xinjiang Medical University,Urumqi 830054,China;Department of Joint Surgery,the First Affiliated Hospital of Xinjiang Medical University,Urumqi 830054,China;Department of Pharmacy,The First Affiliated Hospital of Xinjiang Medical University,Urumqi 830054,China;Key Laboratory of High Incidence Disease Research in Xingjiang,Urumqi 830054,China;Xinjiang Clinical Research Center for Orthopeadics,Urumqi 830054,China)

机构地区：[1]新疆医科大学第一附属医院运动医学科,乌鲁木齐830054 [2]新疆医科大学第一附属医院关节外科,乌鲁木齐830054 [3]新疆医科大学第一附属医院药学部,乌鲁木齐830054 [4]新疆地区高发疾病研究教育部重点实验室,乌鲁木齐830054 [5]新疆骨科疾病临床医学研究中心,乌鲁木齐830054

出　　处：《中华骨与关节外科杂志》2024年第11期997-1006,共10页Chinese Journal of Bone and Joint Surgery

基　　金：国家自然科学基金地区科学基金(82260435);“新疆地区高发疾病研究”教育部重点实验室开放课题(2023A01);新疆维吾尔自治区优秀博士后资助项目(RSSQ00066563)。

摘　　要：目的:探讨超声靶向万古霉素(Vm)负载微泡(MB)对耐甲氧西林金黄色葡萄球菌(MRSA)所致大鼠膝关节急性假体周围感染(PJI)的治疗效果。方法:将60只SD雄性大鼠随机分为假手术(Sham)组、PJI组、超声靶向微泡破坏(UTMD)组、Vm-MBs组及Vm-MBs+UTMD组,每组各12只大鼠。测量并记录各组大鼠体重、术侧股骨远端最大横径,并观察其脓肿情况;拍摄右膝关节X线片,观察假体位置及假体周围骨质破坏的情况;通过扫描电镜观察假体表面生物膜情况;采用平板计数法测定各组大鼠膝关节处假体、骨组织和软组织的菌落数;采用酶联免疫吸附试验(ELISA)法测定血清炎症因子[大鼠α2巨球蛋白(α2-MG)、白介素1β(IL-1β)、白介素6(IL-6)]水平;采用苏木精-伊红(HE)染色评估各组大鼠股骨远端及滑膜炎症;采用TRAP染色观察并比较各组大鼠破骨细胞水平,通过免疫组化染色观察并比较各组大鼠成骨细胞水平;使用Micro CT检测骨密度(BMD)、选定区域骨体积分数(BV/TV)及骨小梁厚度(Tb.Th)。结果:术后前7 d大鼠体重均下降,7 d后体重呈上升趋势,直至第21日再次出现体重轻微下降。术后第1日大鼠股骨远端最大横径明显增加,至第21日,UTMD组大鼠股骨远端最大横径大于Sham组,PJI组、UTMD组大鼠股骨远端最大横径均大于Vm-MBs+UTMD组,第21、28日,UTMD组大鼠股骨远端最大横径大于Vm-MBs组,差异均有统计学意义(P均<0.05)。Sham组与Vm-MBs+UTMD组假体周围均未出现明显的骨质破坏,而PJI组骨质破坏最为严重。PJI组假体表面附着大量MRSA和结构致密的生物膜,UTMD组假体表面MRSA和生物膜数量与PJI组比较明显减少,Vm-MBs组假体表面MRSA和生物膜数量较PJI组和UTMD组明显减少。各组大鼠的假体、骨组织及软组织菌落数整体比较,差异均有统计学意义(P均<0.05);各组大鼠血清炎症因子(1L-6、1L-1β、α2-MG)水平整体比较,差异均有统计学意义(P均<0.05)。PJObjective:To investigate the efficacy of ultrasound-targeted vancomycin-loaded microbubbles(Vm-MBs) in treating periprosthetic joint infection(PJI) caused by methicillin-resistant Staphylococcus aureus(MRSA) in rat knee joints.Methods:Sixty male SD rats were randomly divided into the Sham,PJI,ultrasound-targeted microbubble disruption(UTMD),Vm-MBs,and Vm-MBs+UTMD groups,with 12 rats in each group.The body weight and the maximum transverse diameter of the distal femur were measured and recorded,and the abscesses were observed.X-rays of the right knee joint were taken to evaluate the prosthesis position and the bone destruction around the prosthesis.The biofilm on the prosthetic surface was observed by scanning electron microscopy.The colony counts of prostheses,bone tissue,and soft tissue were determined via plate counting.Serum levels of inflammatory cytokines [rat α2 macroglobulin(α 2-MG),interleukin 1β(IL-1β),and interleukin 6(IL-6)] were determined via enzyme-linked immunosorbent assay(ELISA).Hematoxylin-eosin(HE) staining was used to evaluate distal femur and synovial inflammation in each group.Osteoclasts and osteoblasts were observed and compared in each group via TRAP staining and immunohistochemistry,respectively.Bone mineral density(BMD) were measured via micro-CT,as well as bone volume fraction(BV/TV) and trabecular thickness(Tb.Th) in selected areas.Results:The body weights of the rats decreased in the first 7 days after surgery,then increased,with a slight drop on day 21.The maximum transverse diameter of the distal femur increased significantly on day 1 after surgery.By day 21,the UTMD group showed a greater maximum transverse diameter of the distal femur compared to the Sham group,and both the PJI and UTMD groups had greater diameters than Vm-MBs+UTMD group.On days 21 and 28,the UTMD group had a greater maximum transverse diameter of the distal femur than the Vm-MBs group(P<0.05).The Sham and Vm-MBs+UTMD groups showed minimal bone destruction,while the PJI group showed the most severe bone destr

关 键 词：耐甲氧西林金黄色葡萄球菌 假体周围感染 万古霉素 微泡 超声靶向微泡破坏技术 

分 类 号：R687.4[医药卫生—骨科学]