Hypoxia-inducible factor prolyl hydroxylase inhibitor prevents steroid-associated osteonecrosis of the femoral head in rabbits by promoting angiogenesis and inhibiting apoptosis.
Hypoxia-inducible factor prolyl hydroxylase inhibitor prevents steroid-associated osteonecrosis of the femoral head in rabbits by promoting angiogenesis and inhibiting apoptosis.
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缺氧诱导因子脯氨酰羟化酶抑制剂通过促进血管生成和抑制细胞凋亡来预防类固醇相关的兔股骨头坏死
DOI：
10.1371/journal.pone.0107774
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发表时间：
2014
期刊：
影响因子：
3.7
通讯作者：
Wang K
中科院分区：
文献类型：
--
作者：
Fan L;Li J;Yu Z;Dang X;Wang K
本研究旨在探讨3，4-二羟基苯甲酸乙酯（EDHB）对激素性股骨头坏死（ONFH）的预防作用。新西兰白色家兔随机分为预防组和模型组，每组24只。脂多糖（LPS）联合甲基强的松龙（MPS）诱导骨坏死。预防组于造模前3 d开始隔日腹腔注射EDHB 50 mg/kg，共9次。通过苏木精-伊红（HE）染色证实骨坏死。免疫组化法检测HIF-1α和VEGF的表达。同时分析了血管生成、细胞凋亡和显微结构参数。成功建立兔骨坏死模型，HE染色观察。组织学观察表明，EDHB可降低骨陷窝空泡率和骨坏死发生率。HIF-1α和VEGF的免疫组化染色显示，EDHB治疗抑制了HIF-1α的降解，促进了VEGF的表达。墨汁动脉灌注血管造影及微血管密度分析显示，预防组微血管数量明显多于模型组。TUNEL凋亡检测结果显示，EDHB干预可减少股骨头缺血性坏死中凋亡细胞的数量。显微CT扫描显示治疗组的显微结构参数优于模型组。EDHB通过促进血管生成和抑制骨细胞和造血组织凋亡来预防兔激素相关性股骨头坏死。
The purpose of this study was to investigate the preventive effect of ethyl 3,4-dihydroxybenzoate(EDHB) on steroid-associated femoral head osteonecrosis(ONFH) in a rabbit model. New Zealand white rabbits were randomly divided into two groups (prevention group and model group), each containing 24 rabbits. Osteonecrosis was induced by lipopolysaccharide(LPS) combined with methylprednisolone(MPS). The prevention group received an intraperitoneal injection of EDHB at 50 mg/kg body weight every other day starting three days before establishing rabbit models of osteonecrosis, for a total of nine doses. Osteonecrosis was verified by haematoxylin-eosin (HE) staining. The expression of HIF-1α and VEGF was analyzed by immunohistochemistry. Angiogenesis, apoptosis and microstructural parameters were also analyzed. The rabbit models of osteonecrosis were successfully established and observed by HE staining. Histopathological observations indicated that EDHB reduced the rate of empty lacunae and the incidence of osteonecrosis. Immunohistochemical staining for HIF-1α and VEGF suggested that EDHB therapy inhibited degradation of HIF-1α and promoted expression of VEGF. Ink artery infusion angiography and microvessel density analysis revealed that there were more microvessels in the prevention group than in the model group. The TUNEL apoptosis assay suggested that EDHB intervention could reduce the number of apoptotic cells in avascular osteonecrosis of the femoral head. Micro-CT scanning indicated that the treatment group had better microstructural parameters than the model group. EDHB prevents steroid-associated osteonecrosis of the femoral head in rabbits by promoting angiogenesis and inhibiting apoptosis of bone cells and hematopoietic tissue.
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DOI：
10.1016/j.ocl.2009.01.004
发表时间：
2009-04
期刊：
The Orthopedic clinics of North America
影响因子：
--
作者：
Ajmal M;Matas AJ;Kuskowski M;Cheng EY
通讯作者：
Cheng EY
影响因子：
4.7
作者：
Riddle, Ryan C.;Khatri, Richa;Schipani, Ernestina;Clemens, Thomas L.
通讯作者：
Clemens, Thomas L.
影响因子：
4.3
作者：
Fulda, Simone;Debatin, Klaus-Michael
通讯作者：
Debatin, Klaus-Michael
DOI：
10.1302/0301-620x.86b8.14834
发表时间：
2004-11-01
影响因子：
--
作者：
Calder, JDF;Buttery, L;Polak, JM
通讯作者：
Polak, JM
影响因子：
64.8
作者：
Maxwell, PH;Wiesener, MS;Ratcliffe, PJ
通讯作者：
Ratcliffe, PJ