雌激素缺乏对绝经女性破骨细胞合成及细胞因子分泌的影响
发布时间：2018-08-16 09:11
【摘要】：一.研究背景绝经后骨质疏松是老年女性一种高发的系统性骨骼退行性病变,表现为骨量丢失、微观结构破坏、脆性增加、骨折风险增高。运动干预是预防老年骨质疏松的较好措施,但由于老年女性雌激素分泌减少,骨组织对运动的敏感性下降,因此,本研究探讨老年女性雌激素缺乏导致骨量丢失的机制,为制定有效的运动干预措施提供理论依据。目前,传统的研究方法重点从“雌激素缺乏通过骨细胞上的雌激素受体调节骨代谢变化”这个角度探讨发病机制,雌激素缺乏导致破骨细胞数量迅速增加、活性增强,而代偿性成骨细胞增殖不足以弥补快速骨质流失,骨组织“重建-吸收”平衡关系打破,出现骨质流失加速、骨折风险增高。近年来大量的动物实验报道免疫系统具有调节骨代谢的作用,尤其激活的T细胞可以产生大量的促破骨细胞生成因子(osteoclastogenic cytokines),具有促进破骨细胞分化、成熟及调节活性作用。雌激素缺乏在导致大鼠骨质疏松的同时也伴随着免疫功能的显著变化。这提示：雌激素缺乏导致骨量丢失中免疫细胞及其分泌的细胞因子可能起到重要的调节作用。但是目前大量的实验研究来自动物实验,非常缺乏人体实验资料,因此,还不清楚绝经后雌激素缺乏环境对T细胞及其分泌的促破骨细胞生成因子产生什么样影响,这种影响对破骨细胞的分化、增殖、成熟和凋亡的具有什么调节作用。因此,从T细胞及其分泌的细胞因子角度探讨雌激素缺乏导致骨质流失的机制,对我们深入理解绝经后骨质疏松的发病机制有着十分重要意义。本研究从分子水平探讨理解绝经后骨质疏松的发病机制,为积极预防这一疾病提供新的理论依据。二.研究目的本课题研究雌激素缺乏对绝经女性破骨细胞合成及细胞因子分泌的影响,从免疫学角度探讨绝经后骨质疏松症发病的分子学机制。在通过此研究对运动干预骨质疏松健康科学做前期基础性研究,对未来可能开展的通过体育锻炼的手段来预防和治疗骨质疏松症提供分子学理论基础。三.研究方法研究对象为15名(平均56.5±5.9岁)绝经伴有骨质疏松症(postmenopausal osteoporosis, PostMO)和15名(平均56.65±8.02岁)绝经无骨质疏松症(postmenopause, PostM)的老年女性。采集受试者外周血5毫升分离出单个核细胞,进行破骨细胞培养；采集静脉血5毫升检测血清TNF、IL-6、IL-7、RANKL和OPG水平,同时检测外周血T细胞TNF和RANKL的蛋白及mRNA表达。数据采用SAS9.2软件分析。四.研究结果绝经后骨质疏松(PostMO)女性破骨细胞数量(118±17OCs/well)明显高于绝经无骨质疏松(PostM)女性(34±5 OCs/well) (p0.001),表明破骨细胞数量增加可能是绝经后骨质疏松症的主要发病原因。雌激素缺乏能够明显促进破骨细胞合成因子分泌,PostMO组血清TNF (p0.001)、IL-6 (p=0.048)和RANKL (p=0.006)均高于对照组女性,而OPG和IL-7两组之间无显著差别。流式细胞分析表明PostMO组女性(38%)T细胞表达TNF水平明显高于PostM组女性(1.5%)(p0.01),表明雌激素缺乏通过刺激T细胞表达TNF促进破骨细胞分化、增殖。同时,PostMO组(3.1%)女性RANKL mRNA表达明显高于PostM组(1.2%)女性(p0.05)。五.结论1.绝经伴骨质疏松老年女性破骨细胞合成增多,这可能是老年女性绝经后骨量丢失增加的一个重要原因。2.绝经伴骨质疏松老年女性血清TNF、RANKL、IL-6分泌显著增加,表明雌激素缺乏可导致调节破骨细胞合成的细胞因子分泌增多。3.绝经伴骨质疏松老年女性T细胞的TNF表达明显升高,且RANKL mRNA也明显高于对照组女性,这表明T细胞可能通过增加细胞因子TNF和RANKL表达增加破骨细胞合成。
[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.
【学位授予单位】：浙江师范大学
【学位级别】：硕士
【学位授予年份】：2015
【分类号】：R580
本文编号：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.
【学位授予单位】：浙江师范大学
【学位级别】：硕士
【学位授予年份】：2015
【分类号】：R580
【参考文献】
相关期刊论文 前1条
1 柯贤柱;葛鹏;石芳;;绝经后骨质疏松患者血清脂联素与瘦素和炎性细胞因子的相关性研究[J];中华关节外科杂志(电子版);2012年03期
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