Jiang Yini, Liu Chunfang, Chen Weiheng, Wang Hui, Wang Chao, Lin Na
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.
Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, No. 16, Nanxiaojie, Dongzhimennei, Beijing 100700, China.
Biomed Res Int. 2015;2015:315850. doi: 10.1155/2015/315850. Epub 2015 Feb 11.
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.
类固醇诱导的股骨头坏死（类固醇诱导性股骨头缺血性坏死）是一种骨缺血性坏死疾病。具有显著血管保护特性的川芎嗪（TMP）已广泛用于缺血性神经疾病和心血管疾病的治疗。然而，其在类固醇诱导性股骨头缺血性坏死治疗中的作用尚未得到评估。在本研究中，我们的结果显示，川芎嗪在组织病理学上显著降低了类固醇诱导性股骨头缺血性坏死大鼠的空骨陷窝率、脂肪组织面积和脂肪细胞周长。血液学检查还显示川芎嗪显著降低了血脂水平。根据显微CT定量分析，川芎嗪可改善类固醇诱导性股骨头缺血性坏死大鼠的小梁骨微观结构并增加骨密度。此外，显微CT显示川芎嗪显著增加了股骨头的血管体积、血管表面积、血管体积百分比和血管厚度。有趣的是，川芎嗪治疗可逆转血清和坏死股骨头中VEGF和FLK1蛋白的下调，其在股骨头中的mRNA表达也是如此。总之，这些发现首次表明，川芎嗪可能通过抑制类固醇对VEGF/FLK1信号通路的作用来预防类固醇诱导性股骨头缺血性坏死，并增强股骨头血管生成。
