發(fā)布時(shí)間：2018-09-19 20:52

【摘要】：婦女絕經(jīng)后體內(nèi)雌激素水平顯著下降,發(fā)生骨質(zhì)疏松和骨折的風(fēng)險(xiǎn)顯著增加。DNA甲基化作為表觀遺傳作用機(jī)制之一,與骨質(zhì)疏松的發(fā)生有著重要關(guān)系。雌激素受體α基因甲基化水平升高會(huì)抑制雌激素受體α基因的表達(dá),進(jìn)而影響骨的新陳代謝,但具體作用機(jī)制有待于進(jìn)一步研究。這種甲基化的狀態(tài)是可以逆轉(zhuǎn)的,通過干預(yù)基因甲基化,可以影響骨形成和骨重吸收的過程,進(jìn)而為診斷和治療骨質(zhì)疏松提供新的思路。研究顯示血清同型半胱氨酸(Hcy)會(huì)影響雌激素受體α基因甲基化水平,絕經(jīng)后婦女平均血清Hcy濃度顯著高于絕經(jīng)前婦女,提示血清Hcy濃度可以作為早期篩查骨質(zhì)疏松的指標(biāo)之一;葛根素達(dá)到合適濃度后可抑制成骨細(xì)胞雌激素受體α基因甲基化,增強(qiáng)細(xì)胞ERαmRNA表達(dá),進(jìn)而促使成骨細(xì)胞增殖分化,從而用于骨質(zhì)疏松的治療。通過分析闡明雌激素受體α基因甲基化與骨質(zhì)疏松的關(guān)系,可以早期篩選骨質(zhì)疏松的高危人群,更簡便快捷地診斷骨質(zhì)疏松,為臨床進(jìn)行基因診斷提供理論依據(jù);可以選擇性地開發(fā)調(diào)節(jié)雌激素受體α基因甲基化藥物,從而使治療骨質(zhì)疏松的靶向性更強(qiáng),為骨質(zhì)疏松的基因治療提供理論依據(jù)。
[Abstract]:Estrogen level in postmenopausal women decreased significantly, and the risk of osteoporosis and fracture increased significantly. DNA methylation was one of the epigenetic mechanisms, and had an important relationship with the occurrence of osteoporosis. The increase of methylation level of estrogen receptor 偽 gene will inhibit the expression of estrogen receptor 偽 gene and then affect the metabolism of bone, but the specific mechanism needs to be further studied. This state of methylation can be reversed by intervening gene methylation, which can affect the process of bone formation and bone resorption, thus providing a new idea for the diagnosis and treatment of osteoporosis. The results showed that serum homocysteine (Hcy) could affect the methylation level of estrogen receptor 偽 gene. The average serum Hcy concentration in postmenopausal women was significantly higher than that in premenopausal women, suggesting that serum Hcy concentration could be used as an index for early screening of osteoporosis. Puerarin can inhibit the methylation of estrogen receptor 偽 gene, enhance the expression of ER 偽 mRNA in osteoblasts, and promote the proliferation and differentiation of osteoblasts, which can be used in the treatment of osteoporosis. By analyzing and clarifying the relationship between estrogen receptor 偽 gene methylation and osteoporosis, the high risk population of osteoporosis can be screened early, and the diagnosis of osteoporosis is easier and faster, which provides theoretical basis for clinical gene diagnosis. The methylation drugs regulating estrogen receptor 偽 gene can be selectively developed, which makes the targeted treatment of osteoporosis stronger, and provides theoretical basis for gene therapy of osteoporosis.
【作者單位】： 廣州中醫(yī)藥大學(xué)第三臨床醫(yī)學(xué)院;廣州中醫(yī)藥大學(xué)第三附屬醫(yī)院;海南省中醫(yī)院;廣州中醫(yī)藥大學(xué)第一臨床醫(yī)學(xué)院;廣州市荔灣區(qū)骨傷科醫(yī)院;深圳市寶安區(qū)中醫(yī)院;
【基金】：國家自然科學(xué)基金(81373654) 廣東省自然科學(xué)基金(2015A030313351)
【分類號(hào)】：R580

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