辛伐他汀对肋骨骨折大鼠模型骨愈合的影响以及机制探讨  

Effect of Simvastatin on Bone Healing in Rat Model of Ribfracture and its Mechanism

作　　者：逯娜 黄素伟 张伟巍 张雁 徐昌富 LU Na;HUANG Suwei;ZHANG Weiwei;ZHANG Yan;XU Changfu(Department of Thoracic Surgery,Zhangjiakou First Hospital,Zhangjiakou 075000,China)

机构地区：[1]张家口市第一医院胸外科,河北张家口075000

出　　处：《药物生物技术》2024年第5期496-501,共6页Pharmaceutical Biotechnology

基　　金：河北省医学科学研究课题(No.20221885)。

摘　　要：探究不同剂量辛伐他汀对肋骨骨折大鼠骨组织愈合的影响及其机制,选取60只SPF级SD大鼠建立大鼠肋骨骨折模型,随机分为对照组(n=15)、辛伐他汀低剂量组(n=15),辛伐他汀中剂量组(n=15)、辛伐他汀高剂量组(n=15)。辛伐他汀处理组大鼠造模后分别采用辛伐他汀2.5、5.0、10.0 mg/(kg·d)灌胃,连续4周,于实验终点采用小动物活体成像系统检测肋骨愈合情况;HE染色确定肋骨病理变化;酶联免疫吸附测定(ELISA)检测各组大鼠外周血白细胞介素(interleukin,IL)-1、IL-17、肿瘤坏死因子-α(tumor necrosis factor-α,TNF-α)、骨代谢分子骨保护素(osteoclastogenesis inhibitory factor,OPG)及核因子κB受体活化因子配体(receptor activator of nuclear factor-κB ligand,RANKL)表达水平的变化;蛋白电泳检测成骨细胞骨钙素(osteocalcin,OCN)、Runx2蛋白的表达。小动物活体成像结果显示辛伐他汀低剂量组、辛伐他汀中剂量组和辛伐他汀高剂量组大鼠骨骼愈合优于对照组,并且随着辛伐他汀用量的提高愈合程度提高;HE染色结果表明辛伐他汀低剂量组、辛伐他汀中剂量组和辛伐他汀高剂量组大鼠骨排列方向较为一致,炎性细胞浸润减少,并且随着辛伐他汀用量的提高病理损伤程度降低;ELISA结果表明辛伐他汀低剂量组、辛伐他汀中剂量组和辛伐他汀高剂量组大鼠血清IL-1、IL-17及TNF-α表达水平显著升高,骨代谢相关分子OPG、RANKL表达水平显著升高,OPG/RANKL比值也显著升高,并且随着辛伐他汀使用的剂量增加显著增加,差异具有显著的统计学意义(P<0.01)。蛋白电泳结果显示,与对照组比较,不同剂量辛伐他汀组大鼠OCN、Runx2蛋白表达水平显著升高,并且随着辛伐他汀使用的剂量增加显著增加,差异具有显著的统计学意义(P<0.01)。辛伐他汀对大鼠骨折愈合有促进作用,其机制可能与促进炎症因子释放、激活成骨信号通路OPG/RANKL、骨细胞活性�In order to investgate the effects of different doses of simvastatin on bone tissue healing in rats with rib fractures and its mechanism,60 SPF grade SD rats were selected to establish a rat rib fracture model and randomly divided into control group(n=15),simvastatin low dose group(n=15),simvastatin medium dose group(n=15)and simvastatin high dose group(n=15).Sim-vastatin-treated rats were gavaged with 2.5,5 and 10 mg/(kg·d)for 4 weeks after modelling,and rib healing was detected at theendpoint of the experiment using a small-animal live imaging system;HE staining was used to determine pathological changes in ribs;Enzyme-linked immunosorbent assay(ELISA)was performed to detect changes in peripheral blood levels of interleukin(IL)-1,IL-17,tumour necrosis factor-α(TNF-α),osteoclastogenesis inhibitory factor(OPG),and receptor activator of nuclear factor-κB ligand(RANKL)in all groups of rats.Osteocalcin(OCN)and Runx2 protein expression in osteoblasts were detected by protein electro-phoresis.Small-animal biopsy results showed that rats in the simvastatin low-dose,simvastatin medium-dose and simvastatin high-dose groups had better bone healing than the control group,and the degree of healing increased as simvastatin dosage was increased;the results of HE staining showed that rats in the simvastatin low-dose group,simvastatin medium-dose group and simvastatin high-dose group had a more consistent direction of bone alignment,with a reduction in inflammatory cell infiltration,and the degree of pathological damage was reduced with the increasing in the dosage of simvastatin;ELISA results showed that the expression levels of serum IL-1,IL-17 and TNF-αwere significantly increased in the simvastatin low-dose,simvastatin medium-dose and simvastatin high-dose groups of rats,and the expression levels of bone metabolism-related molecules OPG and RANKL were significantly increased,as well as the OPG/RANKL ratio,which also significantly increased with the increasing dose of simvastatin used,and the difference was statisticall

关 键 词：辛伐他汀 骨折 炎症因子 OPG/RANKL信号通路 骨愈合 机制 大鼠模型 

分 类 号：R683.1[医药卫生—骨科学]