塞来西布通过骨形态发生蛋白/Smad信号通路对胫骨骨折大鼠骨折愈合影响的实验研究  

Experimental study of the effect of cilizeb on fracture healing of tibial fractures in rats through BMP/Smad signaling pathway

作　　者：佟媛旭 刘晨 魏雅丽 白海红 王兴河 Tong Yuanxu;Liu Chen;Wei Yali;Bai Haihong;Wang Xinghe(Clinical Trial Laboratory of Drug Ⅰ,Beijing Shijitan Hospital,Capital Medical University,Beijing 100038,China)

机构地区：[1]首都医科大学附属北京世纪坛医院药物Ⅰ期临床试验研究室,100038

出　　处：《北京医学》2021年第12期1175-1180,共6页Beijing Medical Journal

基　　金：国家科技重大专项(2017ZX09304026002)。

摘　　要：目的探讨塞来昔布通过骨形态发生蛋白(bone morphogenetic proteins,BMP)/Smad信号通路对胫骨骨折大鼠疼痛评分和骨折愈合的影响。方法将48只SD大鼠分为对照组、模型组、塞来昔布低剂量组和塞来昔布高剂量组,每组12只。模型组、塞来昔布低剂量和塞来昔布高剂量组建立胫骨骨折模型。塞来昔布低剂量和塞来昔布高剂量组的灌胃剂量分别为4 mg/(kg·d)和8 mg/(kg·d),连续4周。采用von Frey纤维细丝实验测量机械性痛阈。应用Micro-CT评估骨折愈合情况。采用酶联免疫吸附试验(enzyme linked immunosorbent assay,ELISA)检测血清疼痛介质和炎症细胞因子。采用定量聚合酶链反应(quantitative polymerase chain reaction,qPCR)和Western blot检测骨痂中BMP/Smad信号通路水平。结果建模前4组大鼠痛阈比较,差异无统计学意义(P>0.05)。干预后,模型组痛阈显著低于对照组[(5.14±1.32)g比(13.05±0.76)g],差异有统计学意义(P<0.05),塞来昔布低剂量组[(9.28±1.45)g]和塞来昔布高剂量组[(11.35±1.21)g]痛阈显著高于模型组,塞来昔布高剂量组显著高于低剂量组,差异均有统计学意义(P<0.05)。模型组IL-6[(16.77±2.86)pg/ml]和TNF-α[(22.73±1.57)pg/ml]水平显著高于对照组,塞来昔布低剂量组的IL-6[(10.54±1.24)pg/ml]和TNF-α[(13.87±1.28)pg/ml]水平显著低于模型组,塞来昔布高剂量组的IL-6[(7.74±1.05)pg/ml]和TNF-α[(10.13±1.17)pg/ml]水平显著低于塞来昔布低剂量组,差异均有统计学意义(P<0.05)。模型组5-羟色胺[(431.26±45.89)pg/ml]和P物质[(18.81±2.05)ng/ml]水平显著高于对照组,塞来昔布低剂量组的5-羟色胺[(334.75±34.56)pg/ml]和P物质[(13.97±1.54)ng/ml]水平显著低于模型组,塞来昔布高剂量组的5-羟色胺[(285.29±30.75)pg/ml]和P物质[(10.32±1.10)ng/ml]水平显著低于塞来昔布低剂量组,差异均有统计学意义(P<0.05)。塞来昔布低剂量组和模型组的骨痂体积显著高于塞来昔布高剂量组[(6Objective To explore the effect of celecoxib on the pain score and fracture healing of tibial fracture rats through the bone morphogenetic proteins(BMP)/Smad signaling pathway.Methods A total of 48 rats were divided into control group,model group,low-dose celecoxib group and high-dose celecoxib group,with 12 rats in each group.Tibial fracture models were established in the model group,the low-dose celecoxib group and high-dose celecoxib group.The gavage doses of celecoxib in the low-dose and high-dose groups were 4 mg/(kg·d)and 8 mg/(kg·d),respectively,for four consecutive weeks.The mechanical pain threshold was measured by the von Frey fiber filament test.Fracture healing was assessed by Micro-CT.Serum pain mediators and inflammatory cytokines were detected by ELISA.The level of BMP/Smad signaling pathway in the callus was detected by quantitative PCR(qPCR)and western blot.Results There was no significant difference in pain threshold between the four groups before modeling(P>0.05).After intervention,the pain threshold of the model group was significantly lower than that of the control group[(5.14±1.32)g vs.(13.05±0.76)g],the difference was statistically significant(P<0.05).The pain threshold of the celecoxib low-dose group[(9.28±1.45)g]and the celecoxib highdose group[(11.35±1.21)g]was significantly higher than that of the model group,and the high-dose group was significantly higher than that of the low-dose group,the differences were statistically significant(P<0.05).The levels of IL-6[(16.77±2.86)pg/ml]and TNF-α[(22.73±1.57)pg/ml]in the model group were significantly higher than those in the control group,the levels of IL-6[(10.54±1.24)pg/ml]and TNF-α[(13.87±1.28)pg/ml]in the low-dose celecoxib group were significantly lower than those in the model group,the levels of IL-6[(7.74±1.05)pg/ml]and TNF-α[(10.13±1.17)pg/ml]in the high-dose celecoxib group were significantly lower than those in the low-dose celecoxib group,the differences were statistically significant(P<0.05).The levels of 5-hydroxytr

关 键 词：骨折 骨折愈合 疼痛 塞来昔布 骨形态发生蛋白/Smad信号通路 大鼠 

分 类 号：R683.42[医药卫生—骨科学]