Th17细胞及其相关细胞因子在骨质疏松症发病机制中的作用
发布时间：2018-09-08 16:32
【摘要】：目的:探讨辅助性T细胞17(Th17)及其相关细胞因子白细胞介素-17(IL-17)、白细胞介素-23(IL-23)、白细胞介素-6(IL-6)、核因子κB受体活化因子配体(RANKL)在骨质疏松症(OP)发病机制中的可能作用,并分析Th17细胞及其相关细胞因子IL-17、IL-23、IL-6、RANKL与骨质疏松症患者骨密度之间的相关性,以及骨质疏松症患者的Th17细胞比例与其相关细胞因子IL-17、IL-23、IL-6、RANKL之间的相关性。为进一步探索骨质疏松症的发病机制提供新线索,为临床上骨质疏松症的预防和治疗提供新方法。方法:选取天津市人民医院脊柱外科2014年12月至2016年3月住院期间符合骨质疏松症诊断标准的52例骨质疏松症患者为骨质疏松症组(OP组),其中女性32例,男性20例,年龄55-79岁,平均年龄(69.1±8.6)岁;选取同期在天津市人民医院脊柱外科门诊就诊的骨密度(Bone Mineral Density,BMD)正常的符合入选标准的患者56名为健康对照组(HC组),其中女性34例,男性22例,年龄53-74岁,平均年龄(67.9±8.9)岁。所有研究对象在年龄、体重指数、性别构成比上没有统计学差异,具有可比性。比较OP组和HC组的临床资料BMD及实验室检查指标;运用流式细胞术(Flow Cytometry,FCM)分别检测两组研究对象空腹外周血中Th17细胞比例;运用酶联免疫吸附测定法(Enzyme Linked Immunosorbent Assay,ELISA)分别检测两组研究对象空腹外周血的血清中IL-17、IL-23、IL-6、RANKL的表达水平;进一步分析OP组的空腹外周血中的Th17细胞比例和空腹外周血血清中IL-17、IL-23、IL-6及RANKL的表达水平与骨质疏松症患者骨密度之间的相关性,OP组Th17细胞比例与其相关细胞因子IL-17、IL-23、IL-6、RANKL表达水平之间的相关性,OP组中细胞因子IL-17、IL-23、IL-6、RANKL之间的相关性。结果:(1)在空腹外周血中,OP组的Th17细胞比例为(2.77±0.93)%,HC组的Th17细胞比例为(1.32±0.42)%,两组比较OP组Th17细胞比例较HC组明显增高,两组之间差异具有统计学意义(P0.05)。(2)血清中细胞因子的表达水平,OP组:IL-17为145.89±44.23pg/ml、IL-23为33.98±12.33pg/ml、IL-6为84.98±45.98 pg/ml、RANKL为0.16±0.05μg/L;HC组:IL-17为108.99±32.83pg/ml、IL-23为16.55±6.78 pg/ml、IL-6为23.98±9.88pg/ml、RANKL为0.12±0.04μg/L;两组比较OP组细胞因子IL-17、IL-23、IL-6、RANKL的表达水平分别较HC组细胞因子IL-17、IL-23、IL-6、RANKL的表达水平升高,两组之间差异具有统计学意义(P0.05)。(3)Spearman相关性分析发现:Ⅰ、OP组空腹外周血中Th17细胞比例与骨质疏松患者骨密度降低程度呈正相关(r=0.461,P=0.042),细胞因子RANKL的表达水平与骨质疏松患者骨密度降低程度呈正相关(r=0.552,P=0.032);Ⅱ、OP组中空腹外周血的Th17细胞比例与空腹外周血血清中的IL-17、IL-23、IL-6及RANKL的表达水平呈正相关(r分别为0.362、0.347、0.122、0.875,P分别为0.032、0.031、0.049、0.032);Ⅲ、OP组IL-17的表达水平与IL-6、RANKL的表达水平呈正相关(r分别为0.353、0.435,P分别为0.041、0.043)。结论:1、骨质疏松患者外周血中Th17细胞,细胞因子IL-17、IL-23、IL-6、RANKL的表达水平升高,其中Th17细胞比例、RANKL的表达水平与骨质疏松患者骨密度降低程度呈正相关。2、骨质疏松症患者外周血中Th17细胞与其相关细胞因子IL-17、IL-23、IL-6、RANKL的表达水平呈正相关;IL-17的表达水平与IL-6、RANKL的表达水平呈正相关。3、骨质疏松症患者外周血中Th17细胞及其相关细胞因子IL-17、IL-23、IL-6、RANKL表达增多,提示Th17细胞、IL-17、IL-23、IL-6、RANKL在骨质疏松症的病理发生机制中具有重要作用,但具体的基因转录调控需要更深入的研究。外周血中Th17细胞比例,血清中IL-17、IL-23、IL-6、RANKL的表达水平有可能成为诊断骨质疏松症、评价治疗骨质疏松症疗效的相关指标。
[Abstract]:AIM: To investigate the possible roles of helper T cell 17 (Th17) and its related cytokines interleukin-17 (IL-17), interleukin-23 (IL-23), interleukin-6 (IL-6), nuclear factor kappa B receptor activator ligand (RANKL) in the pathogenesis of osteoporosis (OP), and to analyze the possible roles of Th17 cells and their related cytokines IL-17, IL-23, IL-6, RANKL. The correlation between bone mineral density and the ratio of Th17 cells in osteoporosis patients and their related cytokines, such as IL-17, IL-23, IL-6 and RANKL, provides new clues for further exploring the pathogenesis of osteoporosis and provides new methods for the prevention and treatment of osteoporosis. 52 osteoporosis patients who met the diagnostic criteria of osteoporosis in the spine surgery department of Tianjin People's Hospital from December 2014 to March 2016 were selected as the osteoporosis group (OP group), including 32 females and 20 males aged 55-79 with an average age of 69.1 (+ 8.6) years. 56 healthy controls (HC group) with normal bone mineral density (BMD) were enrolled, including 34 females, 22 males, 53-74 years old, with an average age of (67.9 (+ 8.9) years. There was no significant difference in age, body mass index, sex composition ratio between the OP group and the HC group. BMD and laboratory indexes of the bed materials; Flow Cytometry (FCM) was used to detect the percentage of Th17 cells in the peripheral blood of the two groups; Enzyme Linked Immunosorbent Assay (ELISA) was used to detect the levels of IL-17, IL-23, IL-6 and RANKL in the peripheral blood of the two groups. The correlation between the expression of IL-17, IL-23, IL-6 and RANKL in OP group and the bone mineral density of osteoporosis patients was further analyzed. Results: (1) In the fasting peripheral blood, the proportion of Th17 cells in OP group was (2.77 0.93)% and that in HC group was (1.32 0.42)%. The proportion of Th17 cells in OP group was significantly higher than that in HC group, and the difference between the two groups was statistically significant (P 0.05). (2) The expression of cytokines in serum was significantly higher than that in HC group. OP group: IL-17 was 14.45.89 +44.23 pg/ml, IL-17 was 145.89 +44.89pg/ml, IL-23 was 33.98 [12.33 pg/ml, IL-6 was 84.98 [45.98 pg/ml, RANKL was 0.16 [.16 [0.05 ug/L, RANKL was 0.16], OPgroup: IL-17 was 108.99 [.99 [32.83 pg/ml, HCgroup: IL-17 was 108.99 [, 108.99 [32.83 pg/ml, IL-23 was 16.55 [6.78 P g/ml, IL-23.98 [9.88 pg/ml, RANKL was 0.The expression levels of - 6 and RANKL were respectively Compared with HC group, the expression of cytokines IL-17, IL-23, IL-6 and RANKL increased, the difference between the two groups was statistically significant (P 0.05). (3) Spearman correlation analysis found that: I, OP group fasting peripheral blood Th17 cell ratio and osteoporosis patients with bone density reduction was positively correlated (r = 0.461, P = 0.042), cytokine RANKL expression level and bone mineral density were positively correlated (r = 0.461, P = 0.042). There was a positive correlation between the percentage of Th17 cells in fasting peripheral blood and the levels of IL-17, IL-23, IL-6 and RANKL in serum (r were 0.362, 0.347, 0.122, 0.875, P were 0.032, 0.031, 0.049, 0.032) in OP group and the levels of IL-6, IL-6, IL-6 and RANKL in serum (r were 0.362, 0.347, 0.122, 0.875, P were 0.032, 0.031, 0.049, 0.032 respectively). Conclusion: 1. The expression of Th17 cells, cytokines IL-17, IL-23, IL-6 and RANKL in peripheral blood of osteoporosis patients increased, and the proportion of Th17 cells and the expression of RANKL were positively correlated with the degree of bone mineral density reduction in osteoporosis patients. Th17 cells were positively correlated with the expression of IL-17, IL-23, IL-6 and RANKL, and IL-17 was positively correlated with the expression of IL-6 and RANKL. IL-6, RANKL play an important role in the pathogenesis of osteoporosis, but the specific gene transcription regulation needs more in-depth study.
【学位授予单位】：天津医科大学
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：R580
本文编号：2231073
[Abstract]:AIM: To investigate the possible roles of helper T cell 17 (Th17) and its related cytokines interleukin-17 (IL-17), interleukin-23 (IL-23), interleukin-6 (IL-6), nuclear factor kappa B receptor activator ligand (RANKL) in the pathogenesis of osteoporosis (OP), and to analyze the possible roles of Th17 cells and their related cytokines IL-17, IL-23, IL-6, RANKL. The correlation between bone mineral density and the ratio of Th17 cells in osteoporosis patients and their related cytokines, such as IL-17, IL-23, IL-6 and RANKL, provides new clues for further exploring the pathogenesis of osteoporosis and provides new methods for the prevention and treatment of osteoporosis. 52 osteoporosis patients who met the diagnostic criteria of osteoporosis in the spine surgery department of Tianjin People's Hospital from December 2014 to March 2016 were selected as the osteoporosis group (OP group), including 32 females and 20 males aged 55-79 with an average age of 69.1 (+ 8.6) years. 56 healthy controls (HC group) with normal bone mineral density (BMD) were enrolled, including 34 females, 22 males, 53-74 years old, with an average age of (67.9 (+ 8.9) years. There was no significant difference in age, body mass index, sex composition ratio between the OP group and the HC group. BMD and laboratory indexes of the bed materials; Flow Cytometry (FCM) was used to detect the percentage of Th17 cells in the peripheral blood of the two groups; Enzyme Linked Immunosorbent Assay (ELISA) was used to detect the levels of IL-17, IL-23, IL-6 and RANKL in the peripheral blood of the two groups. The correlation between the expression of IL-17, IL-23, IL-6 and RANKL in OP group and the bone mineral density of osteoporosis patients was further analyzed. Results: (1) In the fasting peripheral blood, the proportion of Th17 cells in OP group was (2.77 0.93)% and that in HC group was (1.32 0.42)%. The proportion of Th17 cells in OP group was significantly higher than that in HC group, and the difference between the two groups was statistically significant (P 0.05). (2) The expression of cytokines in serum was significantly higher than that in HC group. OP group: IL-17 was 14.45.89 +44.23 pg/ml, IL-17 was 145.89 +44.89pg/ml, IL-23 was 33.98 [12.33 pg/ml, IL-6 was 84.98 [45.98 pg/ml, RANKL was 0.16 [.16 [0.05 ug/L, RANKL was 0.16], OPgroup: IL-17 was 108.99 [.99 [32.83 pg/ml, HCgroup: IL-17 was 108.99 [, 108.99 [32.83 pg/ml, IL-23 was 16.55 [6.78 P g/ml, IL-23.98 [9.88 pg/ml, RANKL was 0.The expression levels of - 6 and RANKL were respectively Compared with HC group, the expression of cytokines IL-17, IL-23, IL-6 and RANKL increased, the difference between the two groups was statistically significant (P 0.05). (3) Spearman correlation analysis found that: I, OP group fasting peripheral blood Th17 cell ratio and osteoporosis patients with bone density reduction was positively correlated (r = 0.461, P = 0.042), cytokine RANKL expression level and bone mineral density were positively correlated (r = 0.461, P = 0.042). There was a positive correlation between the percentage of Th17 cells in fasting peripheral blood and the levels of IL-17, IL-23, IL-6 and RANKL in serum (r were 0.362, 0.347, 0.122, 0.875, P were 0.032, 0.031, 0.049, 0.032) in OP group and the levels of IL-6, IL-6, IL-6 and RANKL in serum (r were 0.362, 0.347, 0.122, 0.875, P were 0.032, 0.031, 0.049, 0.032 respectively). Conclusion: 1. The expression of Th17 cells, cytokines IL-17, IL-23, IL-6 and RANKL in peripheral blood of osteoporosis patients increased, and the proportion of Th17 cells and the expression of RANKL were positively correlated with the degree of bone mineral density reduction in osteoporosis patients. Th17 cells were positively correlated with the expression of IL-17, IL-23, IL-6 and RANKL, and IL-17 was positively correlated with the expression of IL-6 and RANKL. IL-6, RANKL play an important role in the pathogenesis of osteoporosis, but the specific gene transcription regulation needs more in-depth study.
【学位授予单位】：天津医科大学
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：R580
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