摘要
目的:观察抗结核药异烟肼(H)、利福平(R)、吡嗪酰胺(Z)缓释涂层在兔脊柱结核模型体内的抗结核性能及组织相容性。方法:选取健康新西兰兔构建L4/5脊柱结核模型,将建模成功的60只模型兔随机分为A、B、C三组,每组20只,其中A组(实验组)病灶清除术后植入包裹HRZ缓释涂层的自体髂骨;B组(对照组)病灶清除术后植入包裹空白涂层的自体髂骨;C组(空白对照组)病灶清除术后单纯植入自体髂骨。术后观察实验兔一般状况及伤口情况;造模前1d、病灶清除术前及术后1d、3d、7d、14d、28d、56d、84d、112d进行血沉(ESR)、C反应蛋白(CRP)检测;术前以及术后14d、28d、56d进行肝肾功能检测;术后28d时A组随机处死5只兔,取心脏、肝脏、脊髓、脾脏及肾脏组织制作病理切片观察;术后56d行脊柱X线片检查后,每组随机处死5只兔在植骨部位局部取材进行骨-材料界面组织病理学观察。结果:术后B组1只兔切口感染,C组1只兔死亡、1只兔截瘫,其余兔术后一般状况良好。三组造模前和手术前的ESR和CRP均无统计学差异(P>0.05);三组手术前的ESR和CRP均较造模前显著性升高(P<0.01)。三组术后1d时ESR和CRP均较术前显著性升高,3d时CRP达到峰值,7d时ESR达到高峰,此后逐渐下降;A组至术后56d时CRP降至造模前水平,84d时ESR降至造模前水平;B、C组至112d时CRP和ESR均仍显著性高于造模前水平(P<0.05)。A组术后7d、56d、84d及112d的ESR和CRP均低于同时间点B、C组(P<0.05),B组与C组同时间点无显著性差异(P>0.05)。三组间术前和术后14d、28d、56d的肝、肾功能指标比较均无统计学差异(P>0.05);三组术后14d、28d、56d的肝、肾功能指标与术前比较均无统计学差异(P>0.05)。术后28d时A组心脏、肝脏、脾脏、脊髓及肾脏组织未见器质性改变及组织损伤征象。术后56d时A组植骨融合情况优于B组及C组(P<0.05),骨-材料界面组织病理切片骨小梁面积显著性高于B组及C组(P<0.01)。结论:HRZ缓释涂层在兔体内具有优良的抗结核性能和组织相容性。
Objectives:The anti-tuberculosis drugs isoniazid(H),rifampicin(R)and pyrazinamide(Z)sustainedrelease coatings were observed in rabbit spinal tuberculosis model for anti-tuberculosis performance and tissue compatibility.Methods:Healthy New Zealand rabbits were selected to construct L4/5 spinal tuberculosis models,and 60 successfully constructed rabbits were randomly divided into 3 groups of 20 rabbits.Group A(ex-perimental group),implanted autologous iliac bone with adhesive HRZ coating after removing the lesion;group B(control group),implanted autologous iliac bone with blank coating after lesion removal;group C(blank con-trol group),implanted autologous iliac bone after lesion removal.The general conditions and wounds of experi-mental rabbits after operation were observed.ESR and CRP were performed 1 d before modeling,preoperationand 1 d,3 d,7 d,14 d,28 d,56 d,84 d,and 112 d after operation.Liver and kidney function tests were performed before and 14 d,28 d,and 56 d after operation.5 rabbits in group A were randomly executed at 28 d after surgery,and their hearts,livers,spinal cord,spleens,and kidney tissues were excised to make pathological sections for observation.Spinal X-ray examination was performed at 56 d after operation,and 5 rabbits were randomly executed in each group to collect material samples from the bone graft site for histopathological observation of the bone-material interface.Results:One rabbit in group B was infected with incision,one rabbit in group C died,one rabbit was paraplegic,and the remaining rabbits were generally in good conditions after operation.The ESR and CRP of the three groups before modeling and before surgery were not statistically different(P>0.05);the ESR and CRP of the three groups before surgery were significantly higher than before modeling(P<0.01).The ESR and CRP of the three groups were significantly higher at 1 d after operation,and the CRP peaked at 3 d,the ESR peaked at 7 d,and then gradually decreased.In group A,the CRP decreased to the pre-model level at 56 d after surgery,and the ESR decreased to the pre-model level at 84 d;in groups B and C,the CRP and ESR were still significantly higher than the pre-model level at 112 d(P<0.05).The ESR and CRP in group A at 7 d,56 d,84 d,and 112 d after operation were lower than those at the same time in groups B and C(P>0.05),and there was no significant difference between groups B and C at the same time(P>0.05).There was no statistically significant difference in liver and kidney function indexes between the three groups before operation and 14 d,28 d,and 56 d(P>0.05);of all three groups,the liver and kidney function indexes at 14 d,28 d,and 56 d after operation were with no statistical difference comparing with those before operation.At 28 d after surgery,there were no organic changes and signs of tissue damage in the heart,liver,spleen,spinal cord and kidney tissues of group A.At 56 d after surgery,the bone graft fusion in group A was better than that in groups B and C(P<0.05),and the area of bone-material interface histopathological sections of group A was significantly bigger than that of groups B and C(P<0.01).Conclusions:HRZ slow-release coating had excellent anti-tuberculosis performance and tissue compatibility.
作者
岳学锋
唐学峰
施建党
吴龙云
YUE Xuefeng;TANG Xuefeng;SHI Jiandang(Department of Orthopedics,the First People′s Hospital of Yinchuan,Yinchuan,750001,China)
出处
《中国脊柱脊髓杂志》
CAS
CSCD
北大核心
2020年第6期558-565,共8页
Chinese Journal of Spine and Spinal Cord
基金
国家自然科学基金(81360275,81760399)
宁夏医科大学校级项目(XM2019154)。
关键词
脊柱结核
抗结核药缓释涂层
异烟肼
利福平
吡嗪酰胺
骨修复
Spinal tuberculosis
Anti-tuberculosis drug sustained-release coating
Isoniazid
Rifampicin
Pyrazinamide
Bone repair