活血接骨汤联合COX-2抑制剂对兔桡骨骨折早期愈合的影响

Effect of Huoxue Jiegu decoction combined with COX-2 inhibitor on radial fracture early healing in rabbits

目的观察活血接骨汤联合COX-2抑制剂对兔桡骨骨折早期愈合的影响。方法将造模后的72只新西兰大白兔随机分为COX-2抑制剂组、空白对照组、联合组,每组24只。其中COX-2抑制剂组给予依托考昔片200 mg/kg灌胃,2次/d;空白对照组给予等剂量蒸馏水灌胃,2次/d;联合组先给予依托考昔片200 mg/kg灌胃,1 h后给予活血接骨汤浓缩口服液灌胃,给药剂量为家兔对人等效剂量的2倍,2次/d。采用自动血黏度测试检测血液流变学指标,并取材进行免疫组化染色,观察骨折愈合的不同时间点外骨膜、内骨膜和骨髓腔骨TGF-β1的表达情况。结果联合组血液流变学各项指标均低于COX-2抑制剂组、空白对照组,差异均有统计学意义(P<0.05)。各时点上,联合组骨外膜TGF-β1表达的MOD值均高于COX-2抑制组、空白对照组(P<0.05)。1w时,各组间内骨膜TGF-β1表达的MOD值比较,差异无统计学意义(P>0.05);2w、3w、4w、6w时,联合组内骨膜TGF-β1表达的MOD值均高于COX-2抑制组、空白对照组(P<0.05)。各时点上,联合组骨髓腔TGF-β1表达的MOD值均高于COX-2抑制组、空白对照组(P<0.05);且1w时COX-2抑制组高于空白对照组,其余时点低于空白对照组(P<0.05)。结论活血接骨汤联合COX-2抑制剂能促进骨折愈合,其机制可能与增加了TGF-β1细胞因子的表达及改善骨折局部血循环有关。

Objective To observe the effect of Huoxue Jiegu decoction combined with COX-2 inhibitoron radial fracture early healing in rabbits. Methods After modeling, 72 New Zealand rabbits were randomlydivided into COX-2 inhibitor group,blank control group and combination group, with 24 rabbits in eachgroup. Intragastric administration of etoricoxib tablets （200 mg/kg） was conducted in the COX-2 inhibitorgroup twice daily, and intragastric administration of distilled water with same volume in the blank control group twice daily. After one hour of intragastric administration of etoricoxib tablets （200 mg/kg）,the group was administered concentrated oral liquid of Huoxue Jiegu decoction using twice the dose in rabbitsconverted to human equivalent dose twice daily. The hmorheological indices were measured by automaticblood viscosity testing equipment. Immunohistochemical staining was performed to observe the TGFp-1 expressions of periosteum, endosteum and marrow cavity at different time points of fracture healing. Results The hemorheological indices of the combination group were lower than those of the COX-2 inhibitorgroup and blank control group （P 〈 0. 05）. At each time point, the MOD value of periosteum TGFp-1 expression in the the combination group was higher than those of the COX-2 inhibitor group and blank control group （ P 〈0. 05） . After 1 week, there was no significant difference in the MOD value of endosteum TGFp-1expression among the three groups （P 〉0. 05 ） . After 2 weeks, 3 weeks, 4 weeks and 6 weeks, the MODvalues of endosteum TGFp-1 expression in the the combination group were higher than those of the COX-2 inhibitor group and blank control group （P 〈 0. 05 ） . At each time point, the MOD value oTGFp-1 expression in the the combination group was higher than those of the Ccontrol group （ P 〈 0. 05 ） . The MOD value of marrow cavity TGFp-1 after 1 week was higher but the values atthe other time points were lower in the COX-2 inhibitor group compared to the blank control group（P 〈0. 05）. Conclusion Huoxue Jiegu decoction combined with COX-2 inhibitor can promote the fracture healing, andthat is probably related to the elevated expression of TGFp-1 and the local blood cfracture site.