小柴胡汤治疗大鼠慢性化脓性颌骨骨髓炎模型疗效的实验研究

Experimental study of curative effect of xiaochaihu decoction in a rat model of chronic pyogenic osteomyelitis of the jaw

目的通过建立大鼠慢性化脓性颌骨骨髓炎模型,探究小柴胡汤对慢性化脓性颌骨骨髓炎愈合的影响。方法选用65只SPF级SD大鼠,通过骨钻制备出圆形骨缺损滴入金黄色葡萄球菌建立慢性化脓性颌骨骨髓模型。1个月后随机抽取5只检测造模结果。模型建立成功后,将剩余大鼠随机均分为4组:A组清创术+生理盐水;B组清创术+小柴胡汤;C组清创术+头孢;D组清创术+小柴胡汤+头孢。给药后2、4、8周每组分别处死5只大鼠,CBCT检测骨缺损范围、酶联免疫吸附法检测炎症因子IL-6、IL-1β水平和免疫组化检测BMP-2,用统计学分析所得的数据。结果CBCT:与A组比较,B组、C组、D组在给药后2、4、8周骨缺损范围均减小(P<0.05),与C组相比,B组、D组骨缺损范围减小(P<0.05),与B组比较,D组骨缺损范围减小(P<0.05)。炎症因子IL-6、IL-1β水平:与A组比较,B组、C组、D组在给药后2、4、8周IL-6、IL-1β水平均降低(P<0.05),B组、D组IL-1β水平均较低于C组(P<0.05),D组IL-6水平低于C组(P<0.05),但B组与C组IL-6水平虽然有差异但无统计学意义(P>0.05),与B组比较,D组IL-1β、IL-6水平均低(P<0.05)。BMP-2免疫组化检测:A组、B组、C组、D组均出现阳性表达,与A组比较,B组、C组、D组在给药后2、4、8周平均光密度高(P<0.05),B组、D组平均光密度高于C组(P<0.05),与B组比较,D组较高(P<0.05)。结论1.用金黄色葡萄球菌在大鼠下颌骨上成功建立慢性化脓性颌骨骨髓炎模型;2.小柴胡汤对大鼠慢性化脓性颌骨骨髓炎有一定的治疗作用,当与头孢联合应用时治疗效果优于小柴胡汤或头孢单独治疗效果。

Objective To explore the healing effect of xiaochaihu decoction in a rat model of chronic pyogenic osteomyelitis of the jaw.Methods Sixty-five specific-pathogen-free rats were used to establish a model of chronic pyogenic osteomyelitis of the jaw,by introducing Staphylococcus aureus into round bone defects prepared using a bone drill.After 1 month,five rats were randomly selected to test the modeling result,and the other rats were divided randomly into four groups:group A,debridement+saline;group B,debridement+xiaochaihu decoction;group C,debridement+cefuroxime;and group D,debridement+xiaochaihu decoction+cefuroxime.Five rats in each group were sacrificed at 2,4,and 8 weeks after administration.The extent of the bone defect was detected by cone beam computed tomography(CBCT),levels of the inflammatory cytokines interleukin(IL)-6 and IL-1βwere detected by enzyme-linked immunosorbent assay,and bone morphogenetic protein-2 was detected by immunohistochemistry.Results CBCT showed that the bone defects in groups B,C,and D had decreased at 2,4,and 8 weeks after administration,compared with group A(P<0.05).In addition,the bone defects were smaller in groups B and D compared with group C(P<0.05),and smaller in group D compared with group B(P<0.05).Levels of IL-6 and IL-1βwere lower in groups B,C,and D compared with group A at 2,4,and 8 weeks after administration,IL-1βlevels were lower in groups B and D compared with group C,and levels of IL-6 were lower in group D compared with C(P<0.05);however,there was no significant difference in IL-6 levels between groups B and C(P>0.05).IL-1βand IL-6 levels were both lower in group D compared with group B(P<0.05).BMP-2 expression was detected in groups A,B,C,and D,with higher mean optical densities in groups B,C,and D compared with group A,higher optical densities in groups B and D compared with group C,and in group D compared with group B at 2,4,and 8 weeks after administration(P<0.05).Conclusions We successfully established a rat model of chronic pyogenic osteomyelitis of the mandible using S.aureus.Xiaochaihu decoction improved chronic pyogenic osteomyelitis,and the therapeutic effect of xiaochaihu decoction combined with cefuroxime was better than that of either drug alone.