穴位埋线干预绝经后骨质疏松症大鼠代谢组学机制研究

Metabonomic Mechanism of Acupoint Catgut Embedding Intervening Postmenopausal Osteoporosis in Rats

目的:应用代谢组学技术初步探讨穴位埋线干预绝经后骨质疏松症的作用机制。方法:将32只3月龄SD雌性大鼠随机分为A空白组、B假手术组、C模型组及D埋线组,每组各8只。选取大鼠单侧“肾俞”“后三里”进行埋线治疗,每周埋线1次,连续治疗12周。进行骨密度检测、血液指标检测及粪便代谢组学分析。结果:埋线组与模型组相比,股骨、胫骨骨密度及血清雌激素水平均升高,差异具有统计学意义(P<0.05)。埋线组与模型组对比,其粪便中花生四烯酸、前列腺素G2、二高γ亚麻酸、丁二酸、维生素A、腺苷甲硫氨酸和黄连素等代谢物含量均出现显著下调,这些代谢物主要出现在血小板活化、亚油酸代谢和5-羟色胺能突触等通路中;埋线组与假手术组相比,粪便孕烯醇酮、色氨酸和胆红素等差异代谢物显著上调,而粪便尿皮质醇、黄尿酸、3-磷酸甘油醛、5-磷酸核酮糖和前列腺素G2等则出现下调。这些代谢物主要参与类固醇激素生物合成、皮质醇合成与分泌、库欣综合征、色氨酸代谢、糖酵解和糖异生、磷酸戊糖途径和维生素B;代谢等通路的活动。结论:穴位埋线可提高骨质疏松症大鼠的骨密度及雌激素水平。可通过纠正激素代谢紊乱、糖脂代谢紊乱及色氨酸代谢紊乱等方面干预绝经后骨质疏松的发生发展进程,并可通过降低花生四烯酸及前列腺素的含量以减少或抑制炎症反应,最终达到治疗骨质疏松的目的。血小板活化、亚油酸代谢及5-羟色胺能突触等通路可能是穴位埋线治疗绝经后骨质疏松症的主要通路。

Objective: To explore the action mechanism of acupoint catgut embedding intervening postmenopausal osteoporosis(PMOP) by metabolomics technology. Methods: 32 female SD rats aged 3 months were randomized into the blank group, the sham operation group, the model group and the catgut embedding group, with 8 rats in each group. PMOP model was established by removing bilateral ovaries in rats. The points chosen in the catgut embedding group was Shenshu and Housanli, the catgut embedding was once per week for 12 weeks. Bone mintral density(BMD) detection, blood indicators test and fecal metabolomics were carried out in the groups. Results: Compared with those in the model group, BMD of femur and tibia, as well as serum level of estrogen increased significantly in the catgut embedding group(P<0.05);the content of faeces arachidonic acid, prostaglandin G2, Dohomo-γ-linolenic acid(DH-γ-LA), succinic acid, vitamin A, adenosylmethionine, berberine and other metabolites, which were mainly found in the pathways of platelet activation, linoleic acid metabolism and serotonin, were significantly down-regulated in the catgut embedding group. Compared with those in the sham operation group, faeces metabolites, such as pregnenolone, tryptophan and bilirubin, were significantly up-regulated, whereas urocortisol, xanthurenic acid, glyceraldehyde-3-phosphate, ribulose-5-phosphate and prostaglandin G2 were down-regulated in the catgut embedding group. Conclusion: Acupoint catgut embedding can improve BMD and estrogen level in PMOP rats. The occurrence and the development process of osteoporosis can be interfered by rectifying the disorder of hormone metabolism, glycolipid metabolism and tryptophan metabolism, and the content of arachidonic acid and prostaglandin can be reduced or suppressed to achieve the goal of treating osteoporosis eventually. Platelet activation, linoleic acid metabolism and serotonin synaptic pathways may be the main pathways of acupoint catgut embedding in the treatment of PMOP.