雌激素缺乏對絕經(jīng)女性破骨細(xì)胞合成及細(xì)胞因子分泌的影響
發(fā)布時(shí)間：2018-08-16 09:11
【摘要】：一.研究背景絕經(jīng)后骨質(zhì)疏松是老年女性一種高發(fā)的系統(tǒng)性骨骼退行性病變,表現(xiàn)為骨量丟失、微觀結(jié)構(gòu)破壞、脆性增加、骨折風(fēng)險(xiǎn)增高。運(yùn)動干預(yù)是預(yù)防老年骨質(zhì)疏松的較好措施,但由于老年女性雌激素分泌減少,骨組織對運(yùn)動的敏感性下降,因此,本研究探討老年女性雌激素缺乏導(dǎo)致骨量丟失的機(jī)制,為制定有效的運(yùn)動干預(yù)措施提供理論依據(jù)。目前,傳統(tǒng)的研究方法重點(diǎn)從“雌激素缺乏通過骨細(xì)胞上的雌激素受體調(diào)節(jié)骨代謝變化”這個(gè)角度探討發(fā)病機(jī)制,雌激素缺乏導(dǎo)致破骨細(xì)胞數(shù)量迅速增加、活性增強(qiáng),而代償性成骨細(xì)胞增殖不足以彌補(bǔ)快速骨質(zhì)流失,骨組織“重建-吸收”平衡關(guān)系打破,出現(xiàn)骨質(zhì)流失加速、骨折風(fēng)險(xiǎn)增高。近年來大量的動物實(shí)驗(yàn)報(bào)道免疫系統(tǒng)具有調(diào)節(jié)骨代謝的作用,尤其激活的T細(xì)胞可以產(chǎn)生大量的促破骨細(xì)胞生成因子(osteoclastogenic cytokines),具有促進(jìn)破骨細(xì)胞分化、成熟及調(diào)節(jié)活性作用。雌激素缺乏在導(dǎo)致大鼠骨質(zhì)疏松的同時(shí)也伴隨著免疫功能的顯著變化。這提示：雌激素缺乏導(dǎo)致骨量丟失中免疫細(xì)胞及其分泌的細(xì)胞因子可能起到重要的調(diào)節(jié)作用。但是目前大量的實(shí)驗(yàn)研究來自動物實(shí)驗(yàn),非常缺乏人體實(shí)驗(yàn)資料,因此,還不清楚絕經(jīng)后雌激素缺乏環(huán)境對T細(xì)胞及其分泌的促破骨細(xì)胞生成因子產(chǎn)生什么樣影響,這種影響對破骨細(xì)胞的分化、增殖、成熟和凋亡的具有什么調(diào)節(jié)作用。因此,從T細(xì)胞及其分泌的細(xì)胞因子角度探討雌激素缺乏導(dǎo)致骨質(zhì)流失的機(jī)制,對我們深入理解絕經(jīng)后骨質(zhì)疏松的發(fā)病機(jī)制有著十分重要意義。本研究從分子水平探討理解絕經(jīng)后骨質(zhì)疏松的發(fā)病機(jī)制,為積極預(yù)防這一疾病提供新的理論依據(jù)。二.研究目的本課題研究雌激素缺乏對絕經(jīng)女性破骨細(xì)胞合成及細(xì)胞因子分泌的影響,從免疫學(xué)角度探討絕經(jīng)后骨質(zhì)疏松癥發(fā)病的分子學(xué)機(jī)制。在通過此研究對運(yùn)動干預(yù)骨質(zhì)疏松健康科學(xué)做前期基礎(chǔ)性研究,對未來可能開展的通過體育鍛煉的手段來預(yù)防和治療骨質(zhì)疏松癥提供分子學(xué)理論基礎(chǔ)。三.研究方法研究對象為15名(平均56.5±5.9歲)絕經(jīng)伴有骨質(zhì)疏松癥(postmenopausal osteoporosis, PostMO)和15名(平均56.65±8.02歲)絕經(jīng)無骨質(zhì)疏松癥(postmenopause, PostM)的老年女性。采集受試者外周血5毫升分離出單個(gè)核細(xì)胞,進(jìn)行破骨細(xì)胞培養(yǎng)；采集靜脈血5毫升檢測血清TNF、IL-6、IL-7、RANKL和OPG水平,同時(shí)檢測外周血T細(xì)胞TNF和RANKL的蛋白及mRNA表達(dá)。數(shù)據(jù)采用SAS9.2軟件分析。四.研究結(jié)果絕經(jīng)后骨質(zhì)疏松(PostMO)女性破骨細(xì)胞數(shù)量(118±17OCs/well)明顯高于絕經(jīng)無骨質(zhì)疏松(PostM)女性(34±5 OCs/well) (p0.001),表明破骨細(xì)胞數(shù)量增加可能是絕經(jīng)后骨質(zhì)疏松癥的主要發(fā)病原因。雌激素缺乏能夠明顯促進(jìn)破骨細(xì)胞合成因子分泌,PostMO組血清TNF (p0.001)、IL-6 (p=0.048)和RANKL (p=0.006)均高于對照組女性,而OPG和IL-7兩組之間無顯著差別。流式細(xì)胞分析表明PostMO組女性(38%)T細(xì)胞表達(dá)TNF水平明顯高于PostM組女性(1.5%)(p0.01),表明雌激素缺乏通過刺激T細(xì)胞表達(dá)TNF促進(jìn)破骨細(xì)胞分化、增殖。同時(shí),PostMO組(3.1%)女性RANKL mRNA表達(dá)明顯高于PostM組(1.2%)女性(p0.05)。五.結(jié)論1.絕經(jīng)伴骨質(zhì)疏松老年女性破骨細(xì)胞合成增多,這可能是老年女性絕經(jīng)后骨量丟失增加的一個(gè)重要原因。2.絕經(jīng)伴骨質(zhì)疏松老年女性血清TNF、RANKL、IL-6分泌顯著增加,表明雌激素缺乏可導(dǎo)致調(diào)節(jié)破骨細(xì)胞合成的細(xì)胞因子分泌增多。3.絕經(jīng)伴骨質(zhì)疏松老年女性T細(xì)胞的TNF表達(dá)明顯升高,且RANKL mRNA也明顯高于對照組女性,這表明T細(xì)胞可能通過增加細(xì)胞因子TNF和RANKL表達(dá)增加破骨細(xì)胞合成。
[Abstract]:Background: Postmenopausal osteoporosis is a high incidence of systemic bone degeneration in elderly women, characterized by loss of bone mass, destruction of microstructure, increased fragility, and increased risk of fracture. Therefore, this study explores the mechanism of bone loss caused by estrogen deficiency in elderly women and provides a theoretical basis for formulating effective exercise intervention measures. Lack of osteoclasts leads to a rapid increase in the number and activity of osteoclasts, while compensatory osteoblasts are not sufficient to compensate for rapid bone loss, bone tissue "reconstruction-absorption" balance is broken, bone loss is accelerated, and the risk of fracture is increased. In recent years, a large number of animal experiments have reported that the immune system plays a role in regulating bone metabolism, especially activation. A large number of osteoclastogenic cytokines (osteoclastogenic cytokines) can be produced by T cells, which can promote the differentiation, maturation and regulation of osteoclasts. But at present, a large number of experimental studies have come from animal experiments, and there is very little experimental data on human beings. Therefore, it is not clear how postmenopausal estrogen deficiency environment affects T cells and osteoclast-stimulating factors secreted by T cells, and how this effect on osteoclasts. Therefore, it is of great significance for us to study the mechanism of osteoporosis induced by estrogen deficiency from the perspective of T cells and cytokines secreted by T cells. Objective To study the effect of estrogen deficiency on osteoclast synthesis and cytokine secretion in postmenopausal women and to explore the molecular mechanism of postmenopausal osteoporosis from the perspective of immunology. To provide molecular basis for the prevention and treatment of osteoporosis by physical exercise. 3. Methods 15 postmenopausal osteoporosis (PostMO) and 15 postmenopausal osteoporosis (PostMO) patients (56.65 [8.02] years old) were studied. The serum levels of TNF, IL-6, IL-7, RANKL and OPG, and the expression of TNF and RANKL protein and mRNA in peripheral blood T cells were detected by 5 ml of peripheral blood from the subjects. 4. The results showed that the number of osteoclasts in postmenopausal women with osteoporosis (PostMO) was significantly higher than that in postmenopausal women without osteoporosis (PostM) (34 The levels of serum TNF (p0.001), IL-6 (p = 0.048) and RANKL (p = 0.006) in PostMO group were higher than those in control group, but there was no significant difference between OPG and IL-7. Flow cytometry analysis showed that the expression of TNF in T cells in PostMO group (38%) was significantly higher than that in PostM group (1.5%) (p0.01). At the same time, the expression of RANKL mRNA in PostMO group (3.1%) was significantly higher than that in PostM group (1.2%) women (p0.05). Conclusion 1. The synthesis of osteoclasts in postmenopausal women with osteoporosis increased, which may be an important reason for the increase of bone loss in postmenopausal women. 2. Serum TNF, R in postmenopausal women with osteoporosis. The secretion of ANKL and IL-6 increased significantly, indicating that estrogen deficiency could lead to the increase of cytokine secretion regulating osteoclast synthesis. 3. The expression of TNF in T cells of senile menopausal women with osteoporosis was significantly increased, and the expression of RANKL mRNA was also significantly higher than that of the control group, indicating that T cells may increase osteoclast fineness by increasing the expression of cytokine TNF and RANKL. Cell synthesis.
【學(xué)位授予單位】：浙江師范大學(xué)
【學(xué)位級別】：碩士
【學(xué)位授予年份】：2015
【分類號】：R580
本文編號：2185538
[Abstract]:Background: Postmenopausal osteoporosis is a high incidence of systemic bone degeneration in elderly women, characterized by loss of bone mass, destruction of microstructure, increased fragility, and increased risk of fracture. Therefore, this study explores the mechanism of bone loss caused by estrogen deficiency in elderly women and provides a theoretical basis for formulating effective exercise intervention measures. Lack of osteoclasts leads to a rapid increase in the number and activity of osteoclasts, while compensatory osteoblasts are not sufficient to compensate for rapid bone loss, bone tissue "reconstruction-absorption" balance is broken, bone loss is accelerated, and the risk of fracture is increased. In recent years, a large number of animal experiments have reported that the immune system plays a role in regulating bone metabolism, especially activation. A large number of osteoclastogenic cytokines (osteoclastogenic cytokines) can be produced by T cells, which can promote the differentiation, maturation and regulation of osteoclasts. But at present, a large number of experimental studies have come from animal experiments, and there is very little experimental data on human beings. Therefore, it is not clear how postmenopausal estrogen deficiency environment affects T cells and osteoclast-stimulating factors secreted by T cells, and how this effect on osteoclasts. Therefore, it is of great significance for us to study the mechanism of osteoporosis induced by estrogen deficiency from the perspective of T cells and cytokines secreted by T cells. Objective To study the effect of estrogen deficiency on osteoclast synthesis and cytokine secretion in postmenopausal women and to explore the molecular mechanism of postmenopausal osteoporosis from the perspective of immunology. To provide molecular basis for the prevention and treatment of osteoporosis by physical exercise. 3. Methods 15 postmenopausal osteoporosis (PostMO) and 15 postmenopausal osteoporosis (PostMO) patients (56.65 [8.02] years old) were studied. The serum levels of TNF, IL-6, IL-7, RANKL and OPG, and the expression of TNF and RANKL protein and mRNA in peripheral blood T cells were detected by 5 ml of peripheral blood from the subjects. 4. The results showed that the number of osteoclasts in postmenopausal women with osteoporosis (PostMO) was significantly higher than that in postmenopausal women without osteoporosis (PostM) (34 The levels of serum TNF (p0.001), IL-6 (p = 0.048) and RANKL (p = 0.006) in PostMO group were higher than those in control group, but there was no significant difference between OPG and IL-7. Flow cytometry analysis showed that the expression of TNF in T cells in PostMO group (38%) was significantly higher than that in PostM group (1.5%) (p0.01). At the same time, the expression of RANKL mRNA in PostMO group (3.1%) was significantly higher than that in PostM group (1.2%) women (p0.05). Conclusion 1. The synthesis of osteoclasts in postmenopausal women with osteoporosis increased, which may be an important reason for the increase of bone loss in postmenopausal women. 2. Serum TNF, R in postmenopausal women with osteoporosis. The secretion of ANKL and IL-6 increased significantly, indicating that estrogen deficiency could lead to the increase of cytokine secretion regulating osteoclast synthesis. 3. The expression of TNF in T cells of senile menopausal women with osteoporosis was significantly increased, and the expression of RANKL mRNA was also significantly higher than that of the control group, indicating that T cells may increase osteoclast fineness by increasing the expression of cytokine TNF and RANKL. Cell synthesis.
【學(xué)位授予單位】：浙江師范大學(xué)
【學(xué)位級別】：碩士
【學(xué)位授予年份】：2015
【分類號】：R580
【參考文獻(xiàn)】
相關(guān)期刊論文 前1條
1 柯賢柱;葛鵬;石芳;;絕經(jīng)后骨質(zhì)疏松患者血清脂聯(lián)素與瘦素和炎性細(xì)胞因子的相關(guān)性研究[J];中華關(guān)節(jié)外科雜志(電子版);2012年03期
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