本文關鍵詞： 糖尿病 肺結(jié)核 氧化應激 B族維生素 累積meta分析　出處：《青島大學》2017年碩士論文　論文類型：學位論文

【摘要】：目的:近年來,發(fā)展中國家迅速上升的糖尿病患病率和仍然嚴重的結(jié)核負擔,使得糖尿病與結(jié)核的關聯(lián)日益彰顯。紅細胞是血液中數(shù)量最多的一種血細胞且富含氧氣,紅細胞膜富含多不飽和脂肪酸,易遭受自由基氧化損傷,是指示氧化應激損傷的敏感標記。有研究表明肺結(jié)核患者體內(nèi)存在氧化與抗氧化失衡,但是目前對于合并糖尿病對肺結(jié)核患者紅細胞(膜)氧化應激水平的影響尚鮮見報道。作為許多代謝途徑中的關鍵性輔酶,B族維生素在代謝中起非常重要的作用,特別是維生素B1、維生素B2、煙酸等,但是B族維生素在肺結(jié)核合并糖尿病(PTB-DM)患者和單純肺結(jié)核患者機體內(nèi)的營養(yǎng)水平是否有差別少有報道。因此,本研究擬通過觀察肺結(jié)核合并糖尿病患者和單純肺結(jié)核(PTB)患者的紅細胞及其質(zhì)膜抗氧化指標和氧化應激指標水平,分析糖尿病對肺結(jié)核患者氧化應激水平的影響;通過檢測機體B族維生素的含量,分析并發(fā)糖尿病對肺結(jié)核患者B族維生素營養(yǎng)狀況的影響。有研究表明,PTB-DM患者較PTB患者更容易出現(xiàn)治療失敗和死亡結(jié)局,因此我們利用累積Meta分析的方法探討糖尿病對肺結(jié)核患者治療結(jié)局的影響。方法:采用流行病學病例對照研究的方法,選取青島市胸科醫(yī)院2015年11月到2016年8月期間45名肺結(jié)核合并糖尿病患者作為病例組,按照年齡、性別進行1:1匹配,選取該醫(yī)院同時期住院的45名單純肺結(jié)核患者作為對照組。運用調(diào)查問卷進行一般情況調(diào)查。采集患者空腹外周靜脈血5m L,分離紅細胞及質(zhì)膜。采用比色法測紅細胞還原型谷胱甘肽(GSH)含量、硫代巴比妥酸法測紅細胞丙二醛(MDA)含量、熒光探針法測紅細胞活性氧族(ROS)含量、羥胺法測紅細胞超氧化物歧化酶(SOD)活性、熒光標記法測紅細胞膜流動性、定磷法測紅細胞膜Na+-K+-ATP酶活性、酶聯(lián)免疫吸附測定法(ELISA法)檢測紅細胞膜8-異構(gòu)前列腺素F2α(8-epi-PGF2α)含量。采用成組病例對照研究的方法探討并發(fā)DM對PTB患者機體B族維生素營養(yǎng)水平的影響。隨機選取在該醫(yī)院確診并住院的PTB-DM患者45例為病例組,同期PTB患者138例為對照組,采用3天24小時膳食回顧法進行膳食攝入水平調(diào)查,并收集年齡、性別、職業(yè)等一般人口學信息。收集患者晨尿40m L,使用熒光分光光度計(F-4500,日本)檢測尿液中硫胺素、核黃素和N,-甲基尼克酰胺的含量,分析患者B族維生素營養(yǎng)狀況。糖尿病對肺結(jié)核治療結(jié)局影響的研究使用累積Meta分析方法。結(jié)果:PTB-DM患者紅細胞GSH含量、SOD活性分別為6.53mg GSH/g Hb、14.15KU/g Hb,紅細胞膜Na+-K+-ATP酶活性為7.10U/m L均明顯低于PTB組(P0.05)。紅細胞膜8-異構(gòu)前列腺素F2α含量兩組間差異無統(tǒng)計學意義(P=0.085),但是數(shù)值上PTB-DM組大于PTB組。PTB-DM組紅細胞氧化產(chǎn)物ROS、MDA含量分別為170.95、0.589nmol/mg Hb明顯高于PTB組(P0.05)。PTB-DM組紅細胞膜流動性偏振度和微粘度分別為0.154、0.900,與PTB組相比明顯升高(P0.05),提示并發(fā)DM時膜流動性下降。尿液B族維生素測定結(jié)果顯示,肺結(jié)核患者維生素B1營養(yǎng)狀況良好,缺乏比例僅為3.3%。維生素B2、煙酸的缺乏比例高達66.7%、76%。PTB組的維生素B1、B2、煙酸營養(yǎng)狀況明顯好于PTB-DM組(118.82μg/g vs 89.70μg/g;18.92μg/g vs11.91μg/g;0.293mg/g vs 0.084mg/g)(P0.05))。膳食攝入水平分析發(fā)現(xiàn),PTB組的煙酸攝入較好達到推薦攝入量的100%。PTB-DM組的煙酸攝入較好,達到了推薦攝入量的80%以上。PTB組和PTB-DM組的維生素B1、B2攝入較差,均未達到推薦攝入量的80%。累積Meta匯總的結(jié)果表明糖尿病是肺結(jié)核2-3月痰涂片陽性(OR=1.71)、失敗或死亡(OR=1.96)、死亡(OR=1.83)、復發(fā)(OR=1.97)、復發(fā)為耐藥結(jié)核(OR=1.5)等治療結(jié)局的危險因素。結(jié)論:并發(fā)糖尿病,可致肺結(jié)核患者紅細胞及其質(zhì)膜氧化應激水平升高;機體維生素B1,維生素B2和煙酸等B族維生素營養(yǎng)水平亦較單純肺結(jié)核患者顯著下降。并發(fā)糖尿病是肺結(jié)核治療后痰涂片陽性、失敗、死亡、復發(fā)等不良治療結(jié)局的危險因素。
[Abstract]:Objective: in recent years, the prevalence of tuberculosis is still a serious burden on developing countries and the rapid rise of diabetes, the diabetes and tuberculosis association becomes more and more obvious. The red blood cells and cells is one of the largest number of oxygen rich blood, erythrocyte membrane rich in polyunsaturated fatty acids, vulnerable to oxidative damage of free radicals, are sensitive a mark indicating the oxidative stress injury. Studies have demonstrated the presence of oxidation and antioxidant imbalance in patients with pulmonary tuberculosis, but the diabetes mellitus on red blood cells in patients with pulmonary tuberculosis (film) oxidative stress level was rarely reported. As a key cofactor in many pathways, vitamin B plays an important role in metabolism in particular, vitamin B1, vitamin B2, niacin, but vitamin B in pulmonary tuberculosis complicated with diabetes mellitus (PTB-DM) patients and the nutritional level of pulmonary tuberculosis in the body is No difference has been rarely reported. Therefore, this study through the observation of patients with pulmonary tuberculosis complicated with diabetes and pulmonary tuberculosis (PTB) patients with red blood cells and plasma antioxidant indexes and oxidative stress index level. The effect of diabetes on pulmonary tuberculosis patients oxidative stress level; by detecting the content of body vitamin B, analysis of the impact of concurrency diabetes on the nutritional status of vitamin B in patients with pulmonary tuberculosis. Studies have shown that PTB-DM patients than in PTB patients more susceptible to treatment failure and death, so we use the method of cumulative Meta analysis the influence of diabetes mellitus on the treatment of pulmonary tuberculosis patients outcome. Methods: the epidemiological case-control study, 45 patients with pulmonary tuberculosis diabetic patients selected from Qingdao Chest Hospital during August 2016 to November 2015 as the case group, according to age, gender, 1:1, select the medicine Hospital inpatients during the same period in 45 cases of simple pulmonary tuberculosis as control group. The use of the questionnaire for general survey. 5m L fasting venous blood were collected from peripheral red blood cells and plasma membrane separation. Colorimetric method was used to measure erythrocyte glutathione (GSH) content, malondialdehyde measuring erythrocyte thiobarbituric acid method (MDA the content of red blood cells) measured ROS fluorescence (ROS) content, superoxide dismutase measuring red blood cell (SOD) hydroxylamine activity, fluorescence labeling method to measure the fluidity of erythrocyte membrane, phosphorus determination method measuring erythrocyte membrane Na+-K+-ATP enzyme activity, enzyme linked immunosorbent assay (ELISA) detection erythrocyte membrane 8- heterogeneous prostaglandin F2 alpha (8-epi-PGF2 alpha) content. Using a case-control study to investigate the effects of vitamin DM with PTB level in B group were randomly selected. The PTB-DM patients in the hospital diagnosed and hospitalized 45 cases Over the same period, 138 PTB patients as the control group, with 3 days of 24 hour dietary recall method to survey and collect dietary intake levels, age, gender, occupation and demographic information were collected. Urinary 40m L, using fluorescence spectrophotometer (F-4500, Japan) urine thiamine, riboflavin and N the content of methyl -, niacin, vitamin B and analysis of the nutritional status of the patients. The impact of diabetes on TB treatment outcomes using cumulative Meta analysis method. Results: the erythrocyte GSH levels in patients with PTB-DM, the activity of SOD were 6.53mg GSH/g Hb, 14.15KU/g Hb, Na+-K+-ATP enzyme activity in erythrocyte membrane of 7.10U/m L were significantly lower than in group PTB (P0.05). There was no significant difference between the two groups of erythrocyte membrane 8- heterogeneous prostaglandin F2 content (P=0.085), but the numerical value of PTB-DM group than PTB group.PTB-DM red blood cell oxidation products ROS, MDA contents were 170.95,0.589nmol /mg Hb was significantly higher than group PTB (P0.05).PTB-DM group of erythrocyte membrane fluidity and microviscosity of the degree of polarization of 0.154,0.900 respectively, compared with the PTB group significantly increased (P0.05), suggesting that with DM membrane fluidity decreased. The determination results of urine B vitamins, vitamin B1 nutritional status of patients with pulmonary tuberculosis, lack of proportion 3.3%. vitamin B2, niacin deficiency ratio as high as 66.7%, 76%.PTB group B2, vitamin B1, niacin nutrition status was better than that of group PTB-DM (118.82 g/g vs 89.70 g/g; 18.92 g/g vs11.91 g/g; 0.293mg/g vs 0.084mg/g (P0.05))). Dietary intake level analysis found that nicotinic acid PTB group better to intake recommended intake of niacin intake of group 100%.PTB-DM is better, more than the recommended intake of 80%.PTB group and PTB-DM group of vitamin B1 and B2 intake is poor, did not reach the recommended intake of 80%. accumulated Meta summary results show that sugar The urine sickness is sputum smear positive pulmonary tuberculosis in 2-3 months (OR=1.71), failure or death (OR=1.96), death (OR=1.83), recurrence (OR=1.97), relapse for drug resistant tuberculosis (OR=1.5) treatment outcome. Conclusion: the risk factors of diabetes, elevated red blood cells in patients with pulmonary tuberculosis and its plasma membrane can cause oxidative stress; the body of vitamin B1, vitamin B2 and niacin levels of vitamin B family than pulmonary tuberculosis complicated with diabetes is significantly decreased. After treatment of tuberculosis with positive sputum smear, failure, death, risk of recurrence and other adverse outcome factors.

【學位授予單位】：青島大學
【學位級別】：碩士
【學位授予年份】：2017
【分類號】：R521;R587.1

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