摘要
目的建立骨折模型，观察抑制表皮生长因子受体信号通路对大鼠股骨骨折愈合的作用。
方法选择80只雄性4周龄SD大鼠，建立股骨骨折模型，随机分为两组：实验组予以表皮生长因子受体信号通路抑制剂吉非替尼[100 mg/（kg·d）]，对照组予以等剂量的甲基纤维素；术后7、14、21、28、42 d行X线检查并获股骨标本，运用Lane and Sandhu X线评分评价骨愈合情况，Image J软件测量骨痂直径大小；通过病理切片行固绿染色观察骨折愈合情况；显微CT（Micro-CT）检测及生物力学检测比较两组骨愈合的差异。
结果X线评分在骨折后第7天（t＝2.234，P＝0.031）、第14天（t＝2.133，P＝0.040）、第21天（t＝2.869，P＝0.008）实验组均优于对照组，骨痂最大直径在第7天（t＝2.874，P＝0.006）、第14天（t＝2.609，P＝0.015）、第21天（t＝2.256，P＝0.033）实验组均小于对照组，第28、42天差异无统计学意义；苏木素-伊红（HE）染色显示，第7、14、21天实验组骨痂组织特别是软骨痂大于对照组，实验组骨折愈合进程较对照组快；Micro-CT检测显示实验组BV（骨体积）骨折后第14天（t＝3.317，P＝0.016）、第21天（t＝3.025，P＝0.023）高于对照组，BV/TV（骨体积分数）第14天（t＝2.967，P＝0.025）、第21天（t＝2.465，P＝0.049）、第28天（t＝3.607，P＝0.011）高于对照组，Tb.N（骨小梁数量）第14天（t＝3.436，P＝0.014）、第21天（t＝3.830，P＝0.009）、第28天（t＝2.872，P＝0.028）高于对照组，Tb.Th（骨小梁厚度）第14天（t＝3.137，P＝0.020）、第21天（t＝2.607，P＝0.040）、第28天（t＝2.6932，P＝0.036）高于对照组，TB.Sp（骨小梁间隔）第21天（t＝2.488，P＝0.047）高于对照组；生物力学检测示骨折后21 d最大载荷（t＝10.846，P＝0.000）、刚度（t＝3.868，P＝0.018）优于对照组，28 d时最大载荷（t＝3.753，P＝0.020）、42 d时破坏能量（t＝2.927，P＝0.043）大于对照组。
结论抑制表皮生长因子受体信号通路对大鼠股骨骨折愈合有促进作用。
ObjectiveEstablishing a rat fracture model of fumer, to observe the effects of the inhibition of epidermal growth factor receptor signaling pathway on the healing of femoral fractures in rats.
Methods50 Spragu-Dawley （SD）rats of 4 weeks old were selected, andestablish the fracture model of the right femur and were randomly divided into two group： the experimental group was given gefitinib [100 mg/（kg·d）] dissolved in 0.5% methyl cellulose by intragastric administration, and the control group was given 0.5% methyl cellulose. X-ray examming after 7, 14, 21, 28 and 42 days of fracture and femoral specimens were collected. Evaluation of fracture healing by using Lane and Sandhu radiographic scoring and the Image J software was used to evaluate callus diameter. Then the differences of bone healing between the two groups were compared by pathological section of hematoxylin and eosin （HE） staining, micro-computed tomography （Micro-CT） analyses and biomechanical testing.
ResultsThe X-ray score of the experimental group were higher and the maximum diameter of callus were lower than those in the control group on the 7 （t=2.234, P=0.031, t=2.874, P=0.006）, 14 day （t=2.133, P=0.040, t=2.609, P=0.015）and 21 day （t=2.869, P=0.008, t=2.872, P=0.028） after the fracture but not on 28 and 42 days. HE staining showed that in the experimental group the callus tissue especially cartilage callus were significantly bigger than the control group at 7, 14, 21 day, and the fracture healing process of the experimental group was faster than that of the control group. Micro-CT examination showed that the levels of Bone Volume （BV） were higher than those of the control group at 14 （t=3.317, P=0.016） and 21 days （t=3.025, P=0.023）, BV/TV were higher than those of the control group at 14 （t=2.967, P=0.025）, 21 days （t=2.465, P=0.049） and 28 days （t=3.607, P=0.011）, Tb. N （Trabecular Number） were higher than those of the control group at 14 （t=3.436, P=0.014）, 21 days （t=3.830, P=0.009）and 28 days （t=2.872, P=0.02）, Trabecular Thickness （Tb.Th） were higher than those of the control group at 14 （t=3.137, P=0.020）, 21 days （t=2.607, P=0.040） and 28 days （t=2.6932, P=0.036）, Trabecular Separation （Tb.Sp） were higher than those of the control group at 21 days （t=2.488, P=0.047） after fracture. Biomechanical examination showed that the maximum load （t=10.846, P=0.000） and stiffness of the 21 days （t=3.868, P=0.018） after fracture were better than that of the control group, the maximum load at 28 days （t=3.753, P=0.020） and the destruction energy of the 42 days （t=2.927, P=0.043）were higher than that of the control group.
ConclusionInhibiting epidermal growth factor receptor signaling pathway could promote the healing of femoral fractures in rats.
作者
袁功武
兰生辉
刘曦明
Yuan Gongwu;Lan Shenghui;Liu Ximing(Wuhan Clinical Institute Affiliated to Southern Medical University, Guangzhou 510515, China;Department of Orthopedics, Wuhan General Hospital of Chinese people＇ s Liberation Army, Wuhan 430070, Chin)
出处
《中华实验外科杂志》
CAS
CSCD
北大核心
2018年第4期731-733,共3页
Chinese Journal of Experimental Surgery
基金
国家自然科学基金（81601902）
关键词
表皮生长因子受体信号通路
股骨骨折
骨折愈合
Epidermal growth factor receptor signaling pathway
Femoral fracture
Fracturehealing
