蓝刺头提取物对骨质疏松症模型大鼠的改善作用及代谢机制
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篇名: 蓝刺头提取物对骨质疏松症模型大鼠的改善作用及代谢机制
TITLE: The improvement effect and metabolic mechanism of Echinops sphaerocephalus extract on osteoporosis model rat
摘要: 目的 研究蒙药蓝刺头提取物对D-半乳糖诱导的骨质疏松症的干预作用及代谢机制。方法选取12周龄雄性Wistar大鼠36只,采用数字随机分组法分为空白组,模型组,骨疏康组,蓝刺头高、中、低剂量组,每组6只。除空白组外其余各组大鼠每日按120mg/kg腹腔注射D-半乳糖,持续注射8周后,蓝刺头高、中、低剂量组分别按878、439、219.5mg/kg灌胃给药,骨疏康组按105.1mg/kg灌胃给药,每日1次,连续给药8周。末次给药后,腹主动脉取血,采用酶联免疫吸附测定法检测大鼠血清中骨代谢指标[羟脯氨酸(HYP)、碱性磷酸酶(ALP)]及氧化应激指标[总抗氧化能力(TAOC)、超氧化物歧化酶(SOD)、丙二醛(MDA)]含量;采用正电子发射断层显像/X线计算机体层成像仪(PET/CT)分析各组大鼠右侧胫骨微结构变化;同时借助代谢组学技术研究蓝刺头对骨质疏松症模型大鼠代谢的调节作用。结果与空白组相比,模型组大鼠HYP、ALP、MDA、骨表面积/骨体积比值(BS/BV)、骨小梁间距(Tb·Sp)均显著升高(P<0.05),TAOC、SOD、骨密度(BMD)、骨体积分数(BVF)、骨小梁厚度(Tb·Th)、骨小梁数量(Tb·N)均显著降低(P<0.05);与模型组相比,各给药组上述指标均有不同程度的逆转。代谢组学研究结果显示,蓝刺头提取物干预后,大鼠血清中花生四烯酸、苯丙氨酸、酪氨酸、色氨酸、异亮氨酸、尿酸等18种代谢物发生显著变化,共涉及花生四烯酸、苯丙氨酸、酪氨酸等15条代谢通路,其中花生四烯酸代谢、苯丙氨酸代谢、酪氨酸代谢为主要影响通路。结论蓝刺头提取物能够有效改善D-半乳糖诱导的氧化应激反应及骨微结构恶化,并通过干预花生四烯酸代谢、氨基酸代谢等途径起效。
ABSTRACT: OBJECTIVE To study the intervention effect and metabolic mechanism of Mongolian medicine Echinops sphaerocephalus extract on D-galactose-induced osteoporosis. METHODS Thirty-six 12-week-old male Wistar rats were selected and randomly divided into blank group, model group, Gushukang group, E. sphaerocephalus high-dose, medium-dose and low- dose groups, with 6 rats in each group. Except for blank group, other groups were intraperitoneally injected with D-galactose at 120 mg/kg per day. After 8 weeks of continuous injection, E. sphaerocephalus high-dose, medium-dose and low-dose groups were given drugs intragastrically at dose of 878, 439, 219.5 mg/kg, respectively. Gushukang group was given Gushukang 105.1 mg/kg intragastrically, once a day, for consecutive 8 weeks. After last administration, blood was collected from the abdominal aorta. Enzyme-linked immunosorbent assay was used to measure the contents of bone metabolism indexes [hydroxyproline (HYP), alkaline phosphatase (ALP)] and oxidative stress indexes [total antioxidant capacity (TAOC), superoxide dismutase (SOD), malondialdehyde (MDA)] in serum of rats. Positron emission tomography/computedtomography (PET/CT) was used to analyze the changes of bone microstructure in right tibia bone. Meanwhile, metabolomic technology was used to study the regulation effect of E. sphaerocephalus on osteoporosis model rats. RESULTS Compared with blank group, HYP, ALP, MDA, ratio of bone surface to bone volume (BS/BV), and trabecular separation (Tb·Sp) in model group were significantly increased (P<0.05), while TAOC, SOD, bone mineral density (BMD), bone volume fraction (BVF), trabecular E-mail:Xpfdc153@163.com thickness (Tb·Th) and trabecular number (Tb·N) were significantly decreased (P<0.05). Compared with model group, above indexes of administration groups were all reversed to different extents. The results of metabonomics study showed that after intervened with the extract of E. sphaerocephalus, 18 metabolites such as arachidonic acid, phenylalanine, tyrosine, tryptophan, isoleucine and uric acid in the serum of rats changed significantly, involving 15 metabolic pathways such as arachidonic acid, phenylalanine and tyrosine, of which arachidonic acid metabolism, phenylalanine metabolism and tyrosine metabolism were the main influencing pathways. CONCLUSIONS E. sphaerocephalus extract can effectively improve D-galactose-induced oxidative stress and the deterioration of bone microstructure, which interferes with metabolic pathways such as arachidonic acid metabolism and amino acid metabolism.
期刊: 2023年第34卷第04期
作者: 董馨;王佳琪;张秀艳;张仲尧;陆景坤;高建萍;薛培凤
AUTHORS: DONG Xin,WANG Jiaqi,ZHANG Xiuyan,ZHANG Zhongyao,LU Jingkun,GAO Jianping,XUE Peifeng
关键字: 蓝刺头;D-半乳糖;代谢组学;骨质疏松;代谢调控
KEYWORDS: Echinops sphaerocephalus; D-galactose; metabolomics; osteoporosis; metabolic regulation
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