title: Tetramethylpyrazine enhances vascularization and prevents osteonecrosis in steroid-treated rats.
abstract: Steroid-induced osteonecrosis of the femoral head (steroid-induced ONFH) is an avascular necrosis disease of bone. Tetramethylpyrazine (TMP), with significant vascular protective properties, has been widely used for the treatments of ischemic neural disorders and cardiovascular diseases. However, its role in the treatment of steroid-induced ONFH has not been evaluated. In this study, our results showed that TMP significantly decreased the ratio of empty lacuna, adipose tissue area, and adipocyte perimeter in steroid-induced ONFH rats histopathologically. TMP also reduced the levels of serum lipid dramatically by haematological examination. According to the micro-CT quantification, TMP could improve the microstructure of the trabecular bone and increases bone mineral density in steroid-induced ONFH rats. Moreover, TMP significantly increased the vessel volume, vessel surface, percentage of vessel volume, and vessel thickness of the femoral heads by micro-CT. Interestingly, the downregulation of VEGF and FLK1 proteins in the sera and necrotic femoral heads could be reversed by TMP treatment, and this was true for their mRNA expressions in femoral heads. In conclusion, these findings suggest for the first time that TMP may prevent steroid-induced ONFH and also enhance femoral head vascularization by inhibiting the effect of steroid on VEGF/FLK1 signal pathway.
authors.affiliation: Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, No. 16, Nanxiaojie, Dongzhimennei, Beijing 100700, China ; School of Pharmacy, Jiangxi University of Traditional Chinese Medicine, Nanchang 330004, China.
authors.forename: Yini
authors.initials: Y
authors.lastname: Jiang
authors.affiliation: Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, No. 16, Nanxiaojie, Dongzhimennei, Beijing 100700, China.
authors.forename: Chunfang
authors.initials: C
authors.lastname: Liu
authors.affiliation: Wangjing Hospital, China Academy of Chinese Medical Sciences, Beijing 100102, China.
authors.forename: Weiheng
authors.initials: W
authors.lastname: Chen
authors.affiliation: Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, No. 16, Nanxiaojie, Dongzhimennei, Beijing 100700, China.
authors.forename: Hui
authors.initials: H
authors.lastname: Wang
authors.affiliation: Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, No. 16, Nanxiaojie, Dongzhimennei, Beijing 100700, China.
authors.forename: Chao
authors.initials: C
authors.lastname: Wang
authors.affiliation: Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, No. 16, Nanxiaojie, Dongzhimennei, Beijing 100700, China.
authors.forename: Na
authors.identifier: 0000-0001-9630-1497
authors.initials: N
authors.lastname: Lin
mesh_terms: D017667:Adipocytes / Q000187:drug effects / Q000378:metabolism; D000273:Adipose Tissue / Q000187:drug effects / Q000378:metabolism; D000818:Animals; D015519:Bone Density / Q000187:drug effects; D015536:Down-Regulation / Q000187:drug effects; D005270:Femur Head / Q000187:drug effects / Q000378:metabolism; D008297:Male; D009389:Neovascularization, Pathologic / Q000188:drug therapy* / Q000378:metabolism; D010020:Osteonecrosis / Q000188:drug therapy* / Q000378:metabolism; D011719:Pyrazines / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D015398:Signal Transduction / Q000187:drug effects; D013256:Steroids / Q000494:pharmacology*; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000378:metabolism
chemical_list: D011719:Pyrazines; D013256:Steroids; D042461:Vascular Endothelial Growth Factor A; D040301:Vascular Endothelial Growth Factor Receptor-2; C017953:tetramethylpyrazine