Th17細(xì)胞及其相關(guān)細(xì)胞因子在骨質(zhì)疏松癥發(fā)病機(jī)制中的作用
發(fā)布時(shí)間：2018-09-08 16:32
【摘要】：目的:探討輔助性T細(xì)胞17(Th17)及其相關(guān)細(xì)胞因子白細(xì)胞介素-17(IL-17)、白細(xì)胞介素-23(IL-23)、白細(xì)胞介素-6(IL-6)、核因子κB受體活化因子配體(RANKL)在骨質(zhì)疏松癥(OP)發(fā)病機(jī)制中的可能作用,并分析Th17細(xì)胞及其相關(guān)細(xì)胞因子IL-17、IL-23、IL-6、RANKL與骨質(zhì)疏松癥患者骨密度之間的相關(guān)性,以及骨質(zhì)疏松癥患者的Th17細(xì)胞比例與其相關(guān)細(xì)胞因子IL-17、IL-23、IL-6、RANKL之間的相關(guān)性。為進(jìn)一步探索骨質(zhì)疏松癥的發(fā)病機(jī)制提供新線索,為臨床上骨質(zhì)疏松癥的預(yù)防和治療提供新方法。方法:選取天津市人民醫(yī)院脊柱外科2014年12月至2016年3月住院期間符合骨質(zhì)疏松癥診斷標(biāo)準(zhǔn)的52例骨質(zhì)疏松癥患者為骨質(zhì)疏松癥組(OP組),其中女性32例,男性20例,年齡55-79歲,平均年齡(69.1±8.6)歲;選取同期在天津市人民醫(yī)院脊柱外科門診就診的骨密度(Bone Mineral Density,BMD)正常的符合入選標(biāo)準(zhǔn)的患者56名為健康對(duì)照組(HC組),其中女性34例,男性22例,年齡53-74歲,平均年齡(67.9±8.9)歲。所有研究對(duì)象在年齡、體重指數(shù)、性別構(gòu)成比上沒有統(tǒng)計(jì)學(xué)差異,具有可比性。比較OP組和HC組的臨床資料BMD及實(shí)驗(yàn)室檢查指標(biāo);運(yùn)用流式細(xì)胞術(shù)(Flow Cytometry,FCM)分別檢測兩組研究對(duì)象空腹外周血中Th17細(xì)胞比例;運(yùn)用酶聯(lián)免疫吸附測定法(Enzyme Linked Immunosorbent Assay,ELISA)分別檢測兩組研究對(duì)象空腹外周血的血清中IL-17、IL-23、IL-6、RANKL的表達(dá)水平;進(jìn)一步分析OP組的空腹外周血中的Th17細(xì)胞比例和空腹外周血血清中IL-17、IL-23、IL-6及RANKL的表達(dá)水平與骨質(zhì)疏松癥患者骨密度之間的相關(guān)性,OP組Th17細(xì)胞比例與其相關(guān)細(xì)胞因子IL-17、IL-23、IL-6、RANKL表達(dá)水平之間的相關(guān)性,OP組中細(xì)胞因子IL-17、IL-23、IL-6、RANKL之間的相關(guān)性。結(jié)果:(1)在空腹外周血中,OP組的Th17細(xì)胞比例為(2.77±0.93)%,HC組的Th17細(xì)胞比例為(1.32±0.42)%,兩組比較OP組Th17細(xì)胞比例較HC組明顯增高,兩組之間差異具有統(tǒng)計(jì)學(xué)意義(P0.05)。(2)血清中細(xì)胞因子的表達(dá)水平,OP組:IL-17為145.89±44.23pg/ml、IL-23為33.98±12.33pg/ml、IL-6為84.98±45.98 pg/ml、RANKL為0.16±0.05μg/L;HC組:IL-17為108.99±32.83pg/ml、IL-23為16.55±6.78 pg/ml、IL-6為23.98±9.88pg/ml、RANKL為0.12±0.04μg/L;兩組比較OP組細(xì)胞因子IL-17、IL-23、IL-6、RANKL的表達(dá)水平分別較HC組細(xì)胞因子IL-17、IL-23、IL-6、RANKL的表達(dá)水平升高,兩組之間差異具有統(tǒng)計(jì)學(xué)意義(P0.05)。(3)Spearman相關(guān)性分析發(fā)現(xiàn):Ⅰ、OP組空腹外周血中Th17細(xì)胞比例與骨質(zhì)疏松患者骨密度降低程度呈正相關(guān)(r=0.461,P=0.042),細(xì)胞因子RANKL的表達(dá)水平與骨質(zhì)疏松患者骨密度降低程度呈正相關(guān)(r=0.552,P=0.032);Ⅱ、OP組中空腹外周血的Th17細(xì)胞比例與空腹外周血血清中的IL-17、IL-23、IL-6及RANKL的表達(dá)水平呈正相關(guān)(r分別為0.362、0.347、0.122、0.875,P分別為0.032、0.031、0.049、0.032);Ⅲ、OP組IL-17的表達(dá)水平與IL-6、RANKL的表達(dá)水平呈正相關(guān)(r分別為0.353、0.435,P分別為0.041、0.043)。結(jié)論:1、骨質(zhì)疏松患者外周血中Th17細(xì)胞,細(xì)胞因子IL-17、IL-23、IL-6、RANKL的表達(dá)水平升高,其中Th17細(xì)胞比例、RANKL的表達(dá)水平與骨質(zhì)疏松患者骨密度降低程度呈正相關(guān)。2、骨質(zhì)疏松癥患者外周血中Th17細(xì)胞與其相關(guān)細(xì)胞因子IL-17、IL-23、IL-6、RANKL的表達(dá)水平呈正相關(guān);IL-17的表達(dá)水平與IL-6、RANKL的表達(dá)水平呈正相關(guān)。3、骨質(zhì)疏松癥患者外周血中Th17細(xì)胞及其相關(guān)細(xì)胞因子IL-17、IL-23、IL-6、RANKL表達(dá)增多,提示Th17細(xì)胞、IL-17、IL-23、IL-6、RANKL在骨質(zhì)疏松癥的病理發(fā)生機(jī)制中具有重要作用,但具體的基因轉(zhuǎn)錄調(diào)控需要更深入的研究。外周血中Th17細(xì)胞比例,血清中IL-17、IL-23、IL-6、RANKL的表達(dá)水平有可能成為診斷骨質(zhì)疏松癥、評(píng)價(jià)治療骨質(zhì)疏松癥療效的相關(guān)指標(biāo)。
[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.
【學(xué)位授予單位】：天津醫(yī)科大學(xué)
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2017
【分類號(hào)】：R580
本文編號(hào)：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.
【學(xué)位授予單位】：天津醫(yī)科大學(xué)
【學(xué)位級(jí)別】：碩士
【學(xué)位授予年份】：2017
【分類號(hào)】：R580
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