普萘洛尔通过miR-92a-3p对小鼠股骨骨折愈合的作用  

Effects of propranolol on femoral fracture healing in mice via miR-92a-3p

作　　者：张津 陈志伟[1] 薛盛中 周文杰 王久夏[1] 申建军[1] ZHANG Jin;CHEN Zhi-wei;XUE Sheng-zhong;ZHOU Wen-jie;WANG Jiu-xia;SHEN Jian-jun(Department of Orthopaedics,Gansu Provincial Hospital of Traditional Chinese Medicine,Lanzhou 730050,Gansu Province,China)

机构地区：[1]甘肃省中医院骨科,甘肃兰州730050

出　　处：《中国临床药理学杂志》2024年第20期3028-3032,共5页The Chinese Journal of Clinical Pharmacology

基　　金：甘肃省卫生健康行业科研计划基金资助项目(GSWSKY2021-035)。

摘　　要：目的探究普萘洛尔通过调控微小RNA-92a-3p(miR-92a-3p)对小鼠股骨骨折愈合的影响及其作用机制。方法把C57BL/6J雄性小鼠随机分成假手术组(等量0.9%NaCl)、模型组(等量0.9%NaCl)、实验组(50 mg·kg^(-1)普萘洛尔灌胃)和抑制药组(在实验组的基础上经尾静脉注射100 mg·kg^(-1)miR-92a-3p inhibitor),除假手术组外,所有小鼠均切断股骨造模。用X线片观察骨愈合情况,用实时定量聚合酶链反应检测股骨组织中miR-92a-3p表达水平,用酶联免疫吸附试验法检测骨形成与骨代谢标记物表达水平,用蛋白印迹法检测通路相关蛋白的表达。结果假手术组、模型组和实验组股骨X线片评分分别为(11.20±2.60)、(4.70±1.50)和(9.60±2.40)分;假手术组、模型组、实验组和抑制药组miR-92a-3p的相对表达水平分别为1.00±0.09、0.73±0.06、0.90±0.07和0.78±0.06,碱性磷酸酶水平分别为(35.21±2.63)、(43.16±3.29)、(67.58±5.37)和(49.62±4.05)U·L^(-1),骨原交联水平分别为(4.57±0.52)、(8.41±0.91)、(4.26±0.67)和(5.73±0.84)ng·mL^(-1),脑源性神经营养因子蛋白相对表达水平分别为1.00±0.14、0.58±0.05、0.83±0.09和0.71±0.06,磷酸化-酪氨酸激酶受体B蛋白相对表达水平分别为1.00±0.12、0.62±0.05、0.89±0.08和0.76±0.07,磷酸化-细胞外调节蛋白激酶蛋白相对表达水平分别为1.00±0.11、0.54±0.04、0.78±0.07和0.65±0.05。模型组的上述指标与假手术组比较,实验组的上述指标与模型组比较,抑制药组的上述指标与实验组比较,在统计学上差异均有统计学意义(P<0.05,P<0.001)。结论普萘洛尔能促进小鼠股骨骨折愈合,可能是上调miR-92a-3p激活脑源性神经营养因子/酪氨酸激酶受体B/细胞外调节蛋白激酶信号通路实现的。Objective To explore the effect of propranolol on femoral fracture healing in mice through regulation of microRNA-92a-3p(miR-92a-3p)and its mechanism.Methods C57BL/6J male mice were randomly divided into sham group(equal amount of 0.9%NaCl),model group(equal amount of 0.9%NaCl),experimental group(50 mg·kg^(-1)propranolol administration),inhibitor group(mice were injected with 100 mg·kg^(-1)miR-92a-3p inhibitor via tail vein on the basis of the experimental group).Femur was severed and molded in all mice except sham operation group.X-ray was used to observe bone healing.Quantitative real time polymerase chain reaction was used to detect the expression of miR-92a-3p in femur tissues.The expression level of bone formation and bone metabolism markers was detected by enzyme linked immunosorbent assay.Western blot was used to detect the expression of pathway-related proteins.Results The X-ray scores of femur in sham group,model group and experimental group were11.20±2.60,4.70±1.50 and 9.60±2.40,respectively;the relative expression levels of miR-92a-3p in sham operation group,model group,experimental group and inhibitor group were 1.00±0.09,0.73±0.06,0.90±0.07and 0.78±0.06;alkaline phosphatase levels were(35.21±2.63),(43.16±3.29),(67.58±5.37)and(49.62±4.05)U·L^(-1),respectively;crosslaps levels were(4.57±0.52),(8.41±0.91),(4.26±0.67)and(5.73±0.84)ng·mL^(-1),respectively;the relative expression levels of brain derived neurotrophic factor were1.00±0.14,0.58±0.05,0.83±0.09 and 0.71±0.06,respectively;the relative expression levels of phosphotyrosine kinase receptor B were 1.00±0.12,0.62±0.05,0.89±0.08 and 0.76±0.07,respectively;the relative expression levels of phospho-extracellular regulated protein kinases were 1.00±0.11,0.54±0.04,0.78±0.07 and0.65±0.05,respectively.The above indexes in the model group were compared with those in the sham group,those in the experimental group were compared with those in the model group,and those in the inhibitor group were compared with those in the experime

关 键 词：普萘洛尔 脑源性神经营养因子 胞外调节蛋白激酶 股骨骨折 酪氨酸激酶受体B 

分 类 号：R972[医药卫生—药品]