Antituberculosis performance and histocompatibility of anti-tuberculosis drug slow-release coating in rabbit spinal tuberculosis model

English Keywords:Spinal tuberculosis  Anti-tuberculosis drug sustained-release coating  Isoniazid  Rifampicin  Pyrazinamide  Bone repair

English Abstract:

  【Abstract】 Objectives: The anti-tuberculosis drugs isoniazid(H), rifampicin(R) and pyrazinamide(Z) sustained-release 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 (experimental 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 control group), implanted autologous iliac bone after lesion removal. The general conditions and wounds of experimental rabbits after operation were observed. ESR and CRP were performed 1d before modeling, preoperationand 1d, 3d, 7d, 14d, 28d, 56d, 84d, and 112d after operation. Liver and kidney function tests were performed before and 14d, 28d, and 56d after operation. 5 rabbits in group A were randomly executed at 28d 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 56d 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 1d after operation, and the CRP peaked at 3d, the ESR peaked at 7d, and then gradually decreased. In group A, the CRP decreased to the pre-model level at 56d after surgery, and the ESR decreased to the pre-model level at 84d; in groups B and C, the CRP and ESR were still significantly higher than the pre-model level at 112d(P<0.05). The ESR and CRP in group A at 7d, 56d, 84d, and 112d 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 14d, 28d, and 56d(P>0.05); of all three groups, the liver and kidney function indexes at 14d, 28d, and 56d after operation were with no statistical difference comparing with those before operation. At 28d 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 56d 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.