并发糖尿病对肺结核患者红细胞（膜）氧化应激及治疗结局影响的研究

发布时间：2018-02-06 00:30

本文关键词： 糖尿病肺结核氧化应激 B族维生素累积meta分析　出处：《青岛大学》2017年硕士论文　论文类型：学位论文

【摘要】：目的:近年来,发展中国家迅速上升的糖尿病患病率和仍然严重的结核负担,使得糖尿病与结核的关联日益彰显。红细胞是血液中数量最多的一种血细胞且富含氧气,红细胞膜富含多不饱和脂肪酸,易遭受自由基氧化损伤,是指示氧化应激损伤的敏感标记。有研究表明肺结核患者体内存在氧化与抗氧化失衡,但是目前对于合并糖尿病对肺结核患者红细胞(膜)氧化应激水平的影响尚鲜见报道。作为许多代谢途径中的关键性辅酶,B族维生素在代谢中起非常重要的作用,特别是维生素B1、维生素B2、烟酸等,但是B族维生素在肺结核合并糖尿病(PTB-DM)患者和单纯肺结核患者机体内的营养水平是否有差别少有报道。因此,本研究拟通过观察肺结核合并糖尿病患者和单纯肺结核(PTB)患者的红细胞及其质膜抗氧化指标和氧化应激指标水平,分析糖尿病对肺结核患者氧化应激水平的影响;通过检测机体B族维生素的含量,分析并发糖尿病对肺结核患者B族维生素营养状况的影响。有研究表明,PTB-DM患者较PTB患者更容易出现治疗失败和死亡结局,因此我们利用累积Meta分析的方法探讨糖尿病对肺结核患者治疗结局的影响。方法:采用流行病学病例对照研究的方法,选取青岛市胸科医院2015年11月到2016年8月期间45名肺结核合并糖尿病患者作为病例组,按照年龄、性别进行1:1匹配,选取该医院同时期住院的45名单纯肺结核患者作为对照组。运用调查问卷进行一般情况调查。采集患者空腹外周静脉血5m L,分离红细胞及质膜。采用比色法测红细胞还原型谷胱甘肽(GSH)含量、硫代巴比妥酸法测红细胞丙二醛(MDA)含量、荧光探针法测红细胞活性氧族(ROS)含量、羟胺法测红细胞超氧化物歧化酶(SOD)活性、荧光标记法测红细胞膜流动性、定磷法测红细胞膜Na+-K+-ATP酶活性、酶联免疫吸附测定法(ELISA法)检测红细胞膜8-异构前列腺素F2α(8-epi-PGF2α)含量。采用成组病例对照研究的方法探讨并发DM对PTB患者机体B族维生素营养水平的影响。随机选取在该医院确诊并住院的PTB-DM患者45例为病例组,同期PTB患者138例为对照组,采用3天24小时膳食回顾法进行膳食摄入水平调查,并收集年龄、性别、职业等一般人口学信息。收集患者晨尿40m L,使用荧光分光光度计(F-4500,日本)检测尿液中硫胺素、核黄素和N,-甲基尼克酰胺的含量,分析患者B族维生素营养状况。糖尿病对肺结核治疗结局影响的研究使用累积Meta分析方法。结果:PTB-DM患者红细胞GSH含量、SOD活性分别为6.53mg GSH/g Hb、14.15KU/g Hb,红细胞膜Na+-K+-ATP酶活性为7.10U/m L均明显低于PTB组(P0.05)。红细胞膜8-异构前列腺素F2α含量两组间差异无统计学意义(P=0.085),但是数值上PTB-DM组大于PTB组。PTB-DM组红细胞氧化产物ROS、MDA含量分别为170.95、0.589nmol/mg Hb明显高于PTB组(P0.05)。PTB-DM组红细胞膜流动性偏振度和微粘度分别为0.154、0.900,与PTB组相比明显升高(P0.05),提示并发DM时膜流动性下降。尿液B族维生素测定结果显示,肺结核患者维生素B1营养状况良好,缺乏比例仅为3.3%。维生素B2、烟酸的缺乏比例高达66.7%、76%。PTB组的维生素B1、B2、烟酸营养状况明显好于PTB-DM组(118.82μg/g vs 89.70μg/g;18.92μg/g vs11.91μg/g;0.293mg/g vs 0.084mg/g)(P0.05))。膳食摄入水平分析发现,PTB组的烟酸摄入较好达到推荐摄入量的100%。PTB-DM组的烟酸摄入较好,达到了推荐摄入量的80%以上。PTB组和PTB-DM组的维生素B1、B2摄入较差,均未达到推荐摄入量的80%。累积Meta汇总的结果表明糖尿病是肺结核2-3月痰涂片阳性(OR=1.71)、失败或死亡(OR=1.96)、死亡(OR=1.83)、复发(OR=1.97)、复发为耐药结核(OR=1.5)等治疗结局的危险因素。结论:并发糖尿病,可致肺结核患者红细胞及其质膜氧化应激水平升高;机体维生素B1,维生素B2和烟酸等B族维生素营养水平亦较单纯肺结核患者显著下降。并发糖尿病是肺结核治疗后痰涂片阳性、失败、死亡、复发等不良治疗结局的危险因素。
[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.

【学位授予单位】：青岛大学
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：R521;R587.1

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