慢性肾衰竭合并正常甲状腺病态综合征患者血清1型脱碘酶与炎症因子水平及相关性研究

发布时间：2018-05-06 18:27

本文选题：慢性肾衰竭 + 1型脱碘酶　；参考：《南昌大学》2017年硕士论文

【摘要】：目的:慢性肾衰竭患者(chronic renal failure,CRF)常合并有正常甲状腺病态综合征(euthyroid sick syndrome,ESS);并伴有炎症因子如肿瘤坏死因子-α(Tumor necrosis factor-α,TNF-α)升高;有研究认为,1型脱碘酶(Type 1 iodothyronine deiodinase DIO-1)在ESS发生机制起重要作用。然而,目前ESS的三碘甲状腺氨酸(Triiodothyronine,T3)水平与DIO-1及炎症因子之间的相关性尚不明确。因此本研究将探讨CRF合并或不合并ESS患者血清DIO-1、白介素-1(IL-1β)、白介素-6(IL-6)、TNF-α及氧化应激因子(8-Isoprostane)的表达变化,并与患者生化检测指标进行相关性分析,明确T3水平对血清DIO-1、IL-1β、IL-6、TNF-α及8-Isoprostane的影响,明确DIO-1对CRF患者炎症因子表达的影响为今后慢性肾衰竭患者低T3状态是否应该接受甲状腺激素替代治疗提供理论及临床参考依据。方法:慢性肾衰竭诊断标准参照2013年慢性肾脏病评估及管理临床实践指南(Kidney Disease Improving Global Outcomes,KDIGO):肌酐清除率(creatinine clearance rate,Ccr)20ml/min或血肌酐(Creatinine,CRE)442umol/L。入选病例为2015年4月至2015年12月在南昌大学第二附属医院肾内科住院的慢性肾衰竭患者。按照ESS诊断标准(血清FT3浓度2.3pg/ml)。将入选病例分为2组,组1:慢性肾衰竭合并ESS组(n=60);组2:慢性肾衰竭不合并ESS组(n=60);组3:正常对照组:通过社区体检及医院体检科收集同年龄段各项指标正常的人群。通过酶联免疫吸附试验(enzyme-linked immunosorbent assay,ELISA)检测以上3组人群血清DIO-1、IL-1β、IL-6、TNF-α以及8-Isoprostane浓度;对比入选者年龄、性别、血压、心率、呼吸频率、体重指数(BMI)、胆固醇、血红蛋白、白蛋白、空腹血糖(FPG)、白细胞、肌酐、尿素氮、尿酸、血清游离三碘甲腺原氨酸(FT3)、血清游离甲状腺素(FT4)、血清促甲状腺激素(TSH)等临床检验指标,并进行相关性分析。结果:1、基本资料:组1和组2间年龄、性别相比,差异无统计学意义,组3由于一次性连续收集的原因,年龄及性别相较于组1、组2有统计学差别。由于CRF患者常伴有贫血、低蛋白血症及高尿酸血症,故CRF组(组1和组2)血红蛋白、白蛋白与组3相比降低,尿酸与组3相比升高。因入组的CRF患者多为糖尿病肾病患者,故CRF组(组1和组2)空腹血糖与组3相比升高。三组间血压、心率、呼吸频率、血白细胞、FT4、TSH均无明显统计学差异。2、血清DIO-1水平:组2 DIO-1表达水平与组1显著升高(2.03±0.16 ng/ml vs 1.31±0.08 ng/ml,p0.001)。组2 DIO-1表达水平与组3显著升高(2.03±0.16ng/ml vs 1.27±0.24 ng/ml,P0.001),组1 DIO-1表达较组3升高,但其差别无统计学意义(1.31±0.08 ng/ml vs 1.27±0.24 ng/ml,p=0.976)。3、血清IL-1β水平:组1IL-1β表达水平和组3相比显著升高(24.69±4.02 pg/ml vs 7.91±1.57 pg/ml,p0.001),组2 IL-1β表达水平和组3相比显著升高(14.64±1.54pg/ml vs 7.91±1.57 pg/ml,p0.05).组1 IL-1β表达较组2升高,但其差别无统计学意义(24.69±4.02 pg/ml vs 14.64±1.54 pg/ml,p=0.065)。4、血清IL-6水平:组1及组2IL-6表达水平和组3相比升高,但其差别无明显统计学意义。5、血清TNF-α水平:组1TNF-α表达水平和组3相比显著性升高(126.96±11.53 ng/ml vs 64.57±7.14 ng/ml,p0.001),组2TNF-α表达水平和组3相比显著性升高(100.67±12.74 ng/ml vs 64.57±7.14 ng/ml,p0.05),组1 TNF-α表达较组2升高,但其差别无统计学意义(126.96±11.53 ng/ml vs 100.67±12.74ng/ml,p=0.339)。6、血清8-Isoprostane水平:组1 8-Isoprostane表达水平和组3相比显著性升高(17±8.05pg/ml vs 4.41±2.47pg/ml,P0.001),组2 8-Isoprostane表达水平和组3相比显著性升高(15.22±8.4pg/ml vs 4.41±2.47pg/ml,p0.001)。组18-Isoprostane表达较组2升高,但其差别无统计学意义(17±8.05pg/ml vs15.22±8.4pg/ml,p=0.516)。7、三组人群血清DIO-1浓度与多变量间的多元逐步回归分析:把生化指标及炎症因子纳入回归方程中进一步多元回归分析后,三组人群血清DIO-1水平与FT3水平呈正相关(r=0.493,p0.001).与肌酐水平呈正相关(r=0.467,p0.001),与血清TNF-α呈负相关(r=-0.603,P0.001),但是血清DIO-1浓度与IL-1β、IL-6无明显相关性。8、三组人群血清8-Isoprostane浓度与多变量间的多元逐步回归分析:把生化指标及炎症因子纳入回归方程中进一步多元回归分析后,三组人群血清8-Isoprostane水平与炎性因子TNF-α(r=0.265,P0.001)及IL-1β(r=0.41.P=0.002)呈正相关。但其与血清FT3、DIO-1无明显相关性。结论:1、CRF患者常伴随炎性因子及氧化应激水平升高。2、CRF不合并ESS患者与CRF合并ESS及健康人群相比,血清DIO-1的表达明显升高,我们推测慢性CRF不合并ESS患者通过代偿性升高血清DIO-1的表达来维持正常FT3水平。3、多元回归分析提示,血清DIO-1水平与血清FT3呈正相关,与TNF-α呈负相关;我们推测升高的DIO-1可以抑制血清炎症因子TNF-α的表达,具体分子机制有待今后进一步探讨。
[Abstract]:Objective: chronic renal failure (CRF) often combines normal thyroid sick syndrome (euthyroid sick syndrome, ESS) with inflammatory factors such as tumor necrosis factor - alpha (Tumor necrosis factor- alpha, TNF- alpha), and there is a study that the mechanism of type 1 deiodontic enzyme (1) occurs in the pathogenesis. However, the correlation between the levels of Triiodothyronine, T3 (T3) and DIO-1 and inflammatory factors in ESS is not yet clear. Therefore, this study will explore the changes in the expression of DIO-1, interleukin -1 (IL-1 beta), interleukins -6 (IL-6), TNF- alpha and oxidative stress factors in patients with or without CRF with or without CRF. The influence of T3 level on serum DIO-1, IL-1 beta, IL-6, TNF- alpha and 8-Isoprostane, and the influence of DIO-1 on the expression of inflammatory factors in CRF patients are clearly defined and the influence of DIO-1 on the expression of inflammatory factors in CRF patients will provide theoretical and clinical reference for whether the low T3 state should accept thyroid hormone replacement therapy in the patients with chronic renal failure in the future. Methods: the criteria for the diagnosis of chronic renal failure refer to the 2013 Kidney Disease Improving Global Outcomes (KDIGO): the creatinine clearance rate (creatinine clearance rate, Ccr) 20ml/min or blood creatinine (Creatinine,) in the second attached to Nanchang University from April 2015 to December 2015. Patients with chronic renal failure hospitalized in the hospital of Nephrology were divided into 2 groups according to the ESS diagnostic standard (serum FT3 concentration 2.3pg/ml). Group 1: chronic renal failure combined with ESS group (n=60); group 2: chronic renal failure without ESS group (n=60); group 3: normal control group: through community physical examination and hospital physical examination department collects the normal age segments of the same age segment index The serum levels of DIO-1, IL-1 beta, IL-6, TNF- a, and 8-Isoprostane in the 3 groups were detected by enzyme-linked immunosorbent assay (ELISA). The age, sex, blood pressure, heart rate, respiratory rate, body mass index (BMI), cholesterol, hemoglobin, albumin, fasting blood glucose (FPG), white blood cells, creatinine were compared. Urea nitrogen, uric acid, serum free three iodide adenoproxine (FT3), serum free thyroxine (FT4), serum thyrotropin (TSH) and other clinical indicators, and correlation analysis. Results: 1, basic data: group 1 and group 2 age, sex, difference is not statistically significant, group 3 due to a one-time continuous collection of causes, age and sex Compared with group 1, group 2 had statistical difference. Because of CRF patients often accompanied by anemia, hypoproteinemia and hyperuricemia, group CRF (group 1 and group 2) hemoglobin, albumin and group 3 decreased, uric acid increased compared with group 3. Because the group of CRF patients were mostly diabetic nephropathy patients, CRF group (group 1 and group 2) increased fasting blood glucose compared with group 3 three. Three There was no significant difference in blood pressure, heart rate, respiratory rate, blood leucocyte, FT4, TSH,.2, and serum DIO-1 level: the level of 2 DIO-1 and group 1 increased significantly (2.03 + 0.16 ng/ml vs 1.31 + 0.08 ng/ml, p0.001). Group 2 DIO-1 expression level and group 3 were significantly higher (2.03 + 0.16ng/ml vs 1.27 + 0.24), and group 1 expressed more 3 But the difference was not statistically significant (1.31 + 0.08 ng/ml vs 1.27 + 0.24 ng/ml, p=0.976).3, and the level of IL-1 beta in group 1IL-1 was significantly higher than that in group 3 (24.69 + 4.02 pg/ml vs 7.91 + 1.57 pg/ml, p0.001), and the level of 2 IL-1 beta in group 2 was significantly higher than that in group 3. The expression of -1 beta was higher than that in group 2, but the difference was not statistically significant (24.69 + 4.02 pg/ml vs 14.64 + 1.54 pg/ml, p=0.065).4, and serum IL-6 level: the level of group 1 and group 2IL-6 increased, but the difference was not statistically significant, but the level of serum TNF- a was significantly higher than that in group 3 (126.96 + 11.53 ng/ml) S 64.57 + 7.14 ng/ml, p0.001), the expression level of group 2TNF- alpha was significantly higher than that of group 3 (100.67 + 12.74 ng/ml vs 64.57 + 7.14 ng/ml, P0.05), and the expression of 1 TNF- a was higher than that of group 2, but the difference was not statistically significant (126.96 + 11.53 ng/ml vs 12.74ng/ml, 0.339). Compared with group 3 (17 + 8.05pg/ml vs 4.41 + 2.47pg/ml, P0.001), the expression level of group 2 8-Isoprostane was significantly higher than that of group 3 (15.22 + 8.4pg/ml vs 4.41 + 2.47pg/ml, p0.001). The expression of 18-Isoprostane expression was higher than that of group 2, but the difference was not statistically significant (17 + 8.05pg/ml vs15.22 +), three groups of blood The multivariate stepwise regression analysis between the concentration of DIO-1 and the multivariable: after the biochemical indexes and inflammatory factors were included in the regression equation, the serum DIO-1 level was positively correlated with the level of FT3 (r=0.493, p0.001). There was a positive correlation with creatinine level (r= 0.467, p0.001), and negative correlation with serum TNF- alpha (r=-0.603, P0.001). But there was no significant correlation between serum DIO-1 concentration and IL-1 beta, IL-6,.8, and the multivariate stepwise regression analysis between the serum 8-Isoprostane concentration and the multivariable in the three groups: after the biochemical indexes and inflammatory factors were included in the regression equation, the serum 8-Isoprostane level and the inflammatory factor TNF- alpha (r=0.265, P0.001) and IL were found in the three groups. -1 beta (r=0.41.P=0.002) is positively correlated. But it has no significant correlation with serum FT3 and DIO-1. Conclusion: 1, CRF patients often accompanied by elevated levels of inflammatory factors and oxidative stress levels.2, CRF without ESS patients with CRF combined ESS and healthy people, the expression of serum DIO-1 significantly increased, we speculate that chronic CRF does not merge compensatory blood by increasing blood. The expression of DIO-1 was maintained to maintain normal FT3 level.3. Multiple regression analysis suggested that serum DIO-1 level was positively related to serum FT3, and negative correlation with TNF- alpha. We speculate that elevated DIO-1 can inhibit the expression of serum inflammatory factor TNF- alpha, and the specific molecular mechanism needs to be further discussed in the future.

【学位授予单位】：南昌大学
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：R692.5;R581

【参考文献】