文献类型：期刊文献

中文题名：激素性股骨头坏死中Hif-1α/VEGF信号轴和H型血管改变的实验研究

英文题名：Changes in Hif-1α/VEGF signal axis and type-H vessels in steroid-induced osteonecrosis of the femoral head

作者：于海洋[1,2];卢增鹏[1,2];汪海燕[2,3];曹盼举[4];姚川江[1,2];曹林忠[1,2];田杰祥[1,2];张晓刚[1,2]

第一作者：于海洋

机构：[1]甘肃中医药大学,兰州730000;[2]甘肃中医药大学附属医院,兰州730000;[3]成都中医药大学,成都610000;[4]宝鸡市中医医院,陕西宝鸡721000

第一机构：甘肃中医药大学

年份：2022

卷号：30

期号：6

起止页码：759

中文期刊名：中国实验动物学报

外文期刊名：Acta Laboratorium Animalis Scientia Sinica

收录：CSTPCD;;北大核心:【北大核心2020】；CSCD:【CSCD2021_2022】；

基金：国家自然科学基金项目(81960832,81860859);甘肃省科技计划资助/自然科学基金(21JR11RA161),甘肃省中医药管理局(GZKP-2021-17,GZKP-2020-31);甘肃中医药大学附属医院院内课题(gzfy-2021-04);宝鸡市卫生健康委员会科研项目(2020-026);张晓刚全国名老中医药专家传承工作室建设项目(国中医药人教函[2022]75号)。

语种：中文

中文关键词：激素性股骨头坏死;H型血管;Hif-1α/VEGF信号轴;实验研究

外文关键词：SINFH;type-H vessels;Hif-1α/VEGF signaling axis;experimental study Conflicts of Interest:The authors declare no conflict of interest.

摘要：目的观察Hif-1α/VEGF信号轴和骨中特异性H型血管在SINFH模型大鼠股骨头中的改变,探究其在骨坏死发生中的改变及意义。方法30只SPF级雄性SD大鼠随机分为空白组(CG)、模型组(MG)、去铁胺组(DFO),每组10只。MG组及DFO组采用甲强龙联合脂多糖法行SINFH造模,CG组及MG组腹腔注射生理盐水,DFO组予腹腔注射250 mg/(kg·d)甲磺酸去铁胺。造模6周后,运用Micro-CT分析观察股骨头微观结构变化,HE染色观察股骨头组织病理变化,免疫荧光染色分析股骨头中H型血管改变,RT-PCR分析股骨头中Hif-1α/VEGF信号轴相关因子的表达。结果Micro-CT分析显示,MG组、DFO组股骨头均出现骨小梁稀疏,但MG组骨小梁出现断裂情况,且股骨头软骨下囊性变形成。HE染色显示,与CG组比,MG组和DFO组均出现明显的股骨头坏死(P<0.01)。免疫荧光染色显示,与CG组比较,MG组股骨头中H型血管量显著下降(P<0.05),与MG组比较DFO组股骨头中H型血管量显著增加(P<0.01)。与CG组比,MG组Osterix^(+)成骨(祖)细胞量均出现下降(P<0.01),与MG组比,DFO组Osterix^(+)成骨(祖)细胞量增加(P<0.01)。RT-PCR分析显示,与CG比较MG组大鼠股骨头Hif-1α、VEGF、Osterix、Runx2(mRNA)表达下降(P<0.01),与MG组比,DFO组Hif-1α、VEGF、Osterix、Runx2(mRNA)表达升高(P<0.01)。结论在SINFH大鼠模型中,激素诱导Hif-1α/VEGF信号轴调控障碍,以及特异性H型血管发生损害,提示骨特异的H型血管损害可能是激素性股骨头坏死的关键发病机制之一。
Objective To observe the changes in the hypoxia-inducible factor 1α(Hif-1α)/vascular endothelial growth factor(VEGF)signaling axis and specific type H vessels in the femoral head of steroid-induced osteonecrosis of the femoral head(SONFH)model rats and explore the role of these changes in the development of osteonecrosis.Methods Thirty specific pathogen-free grade male Sprague-Dawley rats were randomly divided into a control group(CG),model group(MG)and deferoxamine group(DFOG),with 10 rats in each group.The MG and DFOG were treated with methylprednisolone combined with lipopolysaccharide for SONFH modeling,the CG and MG received intraperitoneal injections of normal saline,and the DFOG received intraperitoneal injections of 250 mg/kg deferoxamine mesylate.Six weeks after modeling,micro-computed tomography was performed to observe the microstructural changes of the femoral head,hematoxylin/eosin staining was used to observe the histopathological changes of the femoral head,immunofluorescence staining was used to analyze the changes of type H vessels in the femoral head,and reversetranscription polymerase chain reaction(RT-PCR)was used to analyze expression of HIF-1α/VEGF signaling axis-related factors in the femoral head.Results Micro-computed tomography analysis showed that the femoral head in the MG and DFOG had sparse bone trabeculae,but the bone trabeculae in the MG exhibited fractures and the femoral head showed subchondral cystic degeneration.Hematoxylin/eosin staining showed that compared with the CG,both the MG and DFOG had obvious femoral head necrosis(P<0.01).Immunofluorescence staining showed that compared with the CG,the amount of type H vessels in the femoral head was significantly lower in the MG(P<0.05)and significantly higher in the DFOG(P<0.01).Compared with the CG,the amount of osterix^(+)osteoblast(progenitor)cells was significantly lower in the MG(P<0.01)and significantly higher in the DFOG(P<0.01).RT-PCR showed that the expression of HIF-1α,VEGF,osterix,and Runx2(mRNA)in the femoral head was significantly lower in the MG than CG(P<0.01)and significantly higher in the DFOG than MG(P<0.01).Conclusions Steroid-induced HIF-1α/VEGF signaling axis dysregulation and specific type H vessel damage were observed in this SONFH rat model,suggesting that bone-specific type H vessel damage may be a key pathogenetic factor of SONFH.