發(fā)布時間：2018-05-06 18:27

  本文選題：慢性腎衰竭 + 1型脫碘酶��； 參考：《南昌大學(xué)》2017年碩士論文

【摘要】：目的:慢性腎衰竭患者(chronic renal failure,CRF)常合并有正常甲狀腺病態(tài)綜合征(euthyroid sick syndrome,ESS);并伴有炎癥因子如腫瘤壞死因子-α(Tumor necrosis factor-α,TNF-α)升高;有研究認為,1型脫碘酶(Type 1 iodothyronine deiodinase DIO-1)在ESS發(fā)生機制起重要作用。然而,目前ESS的三碘甲狀腺氨酸(Triiodothyronine,T3)水平與DIO-1及炎癥因子之間的相關(guān)性尚不明確。因此本研究將探討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及氧化應(yīng)激因子(8-Isoprostane)的表達變化,并與患者生化檢測指標(biāo)進行相關(guān)性分析,明確T3水平對血清DIO-1、IL-1β、IL-6、TNF-α及8-Isoprostane的影響,明確DIO-1對CRF患者炎癥因子表達的影響為今后慢性腎衰竭患者低T3狀態(tài)是否應(yīng)該接受甲狀腺激素替代治療提供理論及臨床參考依據(jù)。方法:慢性腎衰竭診斷標(biāo)準(zhǔn)參照2013年慢性腎臟病評估及管理臨床實踐指南(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。入選病例為2015年4月至2015年12月在南昌大學(xué)第二附屬醫(yī)院腎內(nèi)科住院的慢性腎衰竭患者。按照ESS診斷標(biāo)準(zhǔn)(血清FT3濃度2.3pg/ml)。將入選病例分為2組,組1:慢性腎衰竭合并ESS組(n=60);組2:慢性腎衰竭不合并ESS組(n=60);組3:正常對照組:通過社區(qū)體檢及醫(yī)院體檢科收集同年齡段各項指標(biāo)正常的人群。通過酶聯(lián)免疫吸附試驗(enzyme-linked immunosorbent assay,ELISA)檢測以上3組人群血清DIO-1、IL-1β、IL-6、TNF-α以及8-Isoprostane濃度;對比入選者年齡、性別、血壓、心率、呼吸頻率、體重指數(shù)(BMI)、膽固醇、血紅蛋白、白蛋白、空腹血糖(FPG)、白細胞、肌酐、尿素氮、尿酸、血清游離三碘甲腺原氨酸(FT3)、血清游離甲狀腺素(FT4)、血清促甲狀腺激素(TSH)等臨床檢驗指標(biāo),并進行相關(guān)性分析。結(jié)果:1、基本資料:組1和組2間年齡、性別相比,差異無統(tǒng)計學(xué)意義,組3由于一次性連續(xù)收集的原因,年齡及性別相較于組1、組2有統(tǒng)計學(xué)差別。由于CRF患者常伴有貧血、低蛋白血癥及高尿酸血癥,故CRF組(組1和組2)血紅蛋白、白蛋白與組3相比降低,尿酸與組3相比升高。因入組的CRF患者多為糖尿病腎病患者,故CRF組(組1和組2)空腹血糖與組3相比升高。三組間血壓、心率、呼吸頻率、血白細胞、FT4、TSH均無明顯統(tǒng)計學(xué)差異。2、血清DIO-1水平:組2 DIO-1表達水平與組1顯著升高(2.03±0.16 ng/ml vs 1.31±0.08 ng/ml,p0.001)。組2 DIO-1表達水平與組3顯著升高(2.03±0.16ng/ml vs 1.27±0.24 ng/ml,P0.001),組1 DIO-1表達較組3升高,但其差別無統(tǒng)計學(xué)意義(1.31±0.08 ng/ml vs 1.27±0.24 ng/ml,p=0.976)。3、血清IL-1β水平:組1IL-1β表達水平和組3相比顯著升高(24.69±4.02 pg/ml vs 7.91±1.57 pg/ml,p0.001),組2 IL-1β表達水平和組3相比顯著升高(14.64±1.54pg/ml vs 7.91±1.57 pg/ml,p0.05).組1 IL-1β表達較組2升高,但其差別無統(tǒng)計學(xué)意義(24.69±4.02 pg/ml vs 14.64±1.54 pg/ml,p=0.065)。4、血清IL-6水平:組1及組2IL-6表達水平和組3相比升高,但其差別無明顯統(tǒng)計學(xué)意義。5、血清TNF-α水平:組1TNF-α表達水平和組3相比顯著性升高(126.96±11.53 ng/ml vs 64.57±7.14 ng/ml,p0.001),組2TNF-α表達水平和組3相比顯著性升高(100.67±12.74 ng/ml vs 64.57±7.14 ng/ml,p0.05),組1 TNF-α表達較組2升高,但其差別無統(tǒng)計學(xué)意義(126.96±11.53 ng/ml vs 100.67±12.74ng/ml,p=0.339)。6、血清8-Isoprostane水平:組1 8-Isoprostane表達水平和組3相比顯著性升高(17±8.05pg/ml vs 4.41±2.47pg/ml,P0.001),組2 8-Isoprostane表達水平和組3相比顯著性升高(15.22±8.4pg/ml vs 4.41±2.47pg/ml,p0.001)。組18-Isoprostane表達較組2升高,但其差別無統(tǒng)計學(xué)意義(17±8.05pg/ml vs15.22±8.4pg/ml,p=0.516)。7、三組人群血清DIO-1濃度與多變量間的多元逐步回歸分析:把生化指標(biāo)及炎癥因子納入回歸方程中進一步多元回歸分析后,三組人群血清DIO-1水平與FT3水平呈正相關(guān)(r=0.493,p0.001).與肌酐水平呈正相關(guān)(r=0.467,p0.001),與血清TNF-α呈負相關(guān)(r=-0.603,P0.001),但是血清DIO-1濃度與IL-1β、IL-6無明顯相關(guān)性。8、三組人群血清8-Isoprostane濃度與多變量間的多元逐步回歸分析:把生化指標(biāo)及炎癥因子納入回歸方程中進一步多元回歸分析后,三組人群血清8-Isoprostane水平與炎性因子TNF-α(r=0.265,P0.001)及IL-1β(r=0.41.P=0.002)呈正相關(guān)。但其與血清FT3、DIO-1無明顯相關(guān)性。結(jié)論:1、CRF患者常伴隨炎性因子及氧化應(yīng)激水平升高。2、CRF不合并ESS患者與CRF合并ESS及健康人群相比,血清DIO-1的表達明顯升高,我們推測慢性CRF不合并ESS患者通過代償性升高血清DIO-1的表達來維持正常FT3水平。3、多元回歸分析提示,血清DIO-1水平與血清FT3呈正相關(guān),與TNF-α呈負相關(guān);我們推測升高的DIO-1可以抑制血清炎癥因子TNF-α的表達,具體分子機制有待今后進一步探討。
[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.

【學(xué)位授予單位】：南昌大學(xué)
【學(xué)位級別】：碩士
【學(xué)位授予年份】：2017
【分類號】：R692.5;R581

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