抑制CX3C趋化因子受体1对细菌性骨髓炎大鼠骨缺损的改善作用

Effect of inhibiting CX3C chemokine receptor 1 on improvement of bone defect of rats with bacterial osteomyelitis

目的探讨抑制CX3C趋化因子受体1(CX3CR1)对细菌性骨髓炎大鼠骨缺损的改善作用。方法采用双侧胫骨近端制造骨缺损来制备细菌性骨髓炎模型,选取60只SPF级健康雄性Wistar大鼠随机分为对照组、感染组和治疗组,每组各20只,对照组骨缺损残腔不作处理,其余两组均置入蘸有金黄色葡萄球菌悬液的棉条,治疗组向残腔内注射CX3CR1中和抗体。术后2周观察三组的创口愈合情况,肉眼观察胫骨标本并进行Rissing评分,右胫骨X线Norden评分,采用酶联免疫吸附法检测血清和胫骨造模病灶周围组织中的炎症因子[白介素(IL)-1β、IL-6和超敏C-反应蛋白(hs-CRP)]水平。结果术后2周观察,对照组均为甲级愈合,感染组乙级愈合率和丙级愈合率分别为20.00%(4/20)和80.00%(16/20),治疗组分别为45.00%(9/20)和55.00%(11/20),各组创口愈合程度的差异有统计学意义(P<0.05);感染组大鼠术后2周的体温、Rissing评分和Nordan评分及炎症因子IL-1β、IL-6和hs-CRP水平,与对照组比较均升高(P<0.05);治疗组上述指标与感染组比较均降低(P<0.05);治疗组病灶周围组织细菌负荷较对照组升高,较感染组降低(P<0.05)。结论抑制CX3CR1可改善细菌性骨髓炎大鼠骨缺损,促进愈合并改善病理改变,可能与其降低细胞感染引起的炎症反应有关。

OBJECTIVE To explore the effect of inhibiting CX3 C chemokine receptor 1(CX3 CR1)on improvement of bone defect of rats with bacterial osteomyelitis.METHODS The bone defect was manufactured to prepare bacterial osteomyelitis model by using bilateral proximal tibia,60 SPF healthy male Wistar rats were selected and randomly divided into the control group,the infection group and treatment group,with 20 rats in each group.The bone defect in the residual cavity of the control group was not treated,the rest of the two groups were put into cotton dips in suspension of Staphylococcus aureus,the residual cavity of the treatment group was injected with CX3 CR1 to neutralize antibody.The wound healing of the three groups was observed 14 days after surgery,the tibial specimens were observed with the naked eyes,the Rissing scoring was performed,the right tibial X-ray Norden score was scored,and the levels of inflammatory factors interleukin-1β(IL-1β),IL-6 and hypersensitive C-reactive protein(hs-CRP)in serum and tibial model lesion tissues were detected by enzyme-linked immunosorbent assay.RESULTS After the surgery for 2 weeks,all of the rats in the control group were grade A healing,the grade B healing rate and grade C healing rate were respectively 20.00%(4/20)and 80.00%(16/20)in the infection group,45.00%(9/20)and 55.00%(11/20)in the treatment group;there was significant difference in the degree of wound healing among the three groups(P<0.05).The body temperature,Rissing score and Nordan score,as well as levels of inflammatory factors IL-1β,IL-6 and hs-CRP were significantly higher in the infection group than in the control group after the surgery for 2 weeks(P<0.05);the above indexes of the treatment group were significantly lower than those of the infection group(P<0.05).The bacterial load in the surrounding tissues of the treatment group was significantly higher than that of the control group(P<0.05).CONCLUSION The inhibition of CX3 CR1 may facilitate the improvement of bone defects of the rats with bacterial osteomyelitis,promote healing,and improve pathological changes,which may be related to the reduction of inflammatory response caused by cell infection.