内源性硫化氢及活性氧在慢性阻塞性肺疾病中的作用

发布时间：2018-05-30 19:31

本文选题：慢性阻塞性肺疾病 + 内源性硫化氢　；参考：《宁夏医科大学》2017年硕士论文

【摘要】：目的观察慢性阻塞性肺疾病急性加重期(AECOPD)患者血清硫化氢(H_2S)、活性氧(ROS)和核转录因子-κB(NF-κB)水平变化,并探讨其临床意义。方法选择2015年11月-2016年12月就诊于宁夏回族自治区人民医院呼吸内科的AECOPD患者60例(根据COPD全球创议(GOLD)分级标准[1],其中根据COPD气流受限严重程度分级(GOLD):II级患者25例,III级患者21例,IV级患者14例),根据中华医学会呼吸病学分会颁布的《慢性阻塞性肺疾病诊治指南》2013年修订版[2]诊断标准入组。正常对照组选择同期在我院体检中心体检的健康者60例,两组间年龄、性别、体重指数、吸烟指数指标匹配。将入组的AECOPD患者再分为治疗前和治疗后两组。治疗后组的定义:入组的60例AECOPD患者给予吸氧、抗感染、解痉平喘等一致的常规治疗方案(不包括使用维生素类药物),症状缓解达到出院标准时为治疗后组。根据入院当时超声心动图检查的结果(肺动脉收缩压(PASP)50mm Hg为肺动脉高压),设立COPD合并肺动脉高压组及COPD非肺动脉高压组。使用酶联免疫法(ELISA)测定AECOPD患者治疗前、治疗后及正常对照组血清H_2S、ROS和NF-κB的水平,并与Pa CO2、Pa O2、第一秒用力呼气容积占预计值百分比(FEV1%预计值)、PASP、六分钟步行实验(6MWT)、改进的呼吸困难评分(MMRC)、血常规中白细胞计数(WBC)、中性粒细胞绝对值(GRA)及超敏C反应蛋白(CRP)等进行相关性分析。结果1.正常对照组与AECOPD组之间在性别、年龄、体重指数及吸烟指数上统计学均无显著性差异(P0.05),AECOPD组FEV1/FVC明显低于正常对照组(P0.05)。2.AECOPD治疗前后及正常对照组三组的血清H_2S、ROS和NF-κB的水平变化:(1)AECOPD时ROS水平明显升高:AECOPD治疗前组血清ROS(569.74±73.97)IU/ml、治疗后组(396.93±83.40)IU/ml(P0.05);正常对照组(285.01±68.89)IU/ml(P0.05);(2)AECOPD时NF-κB水平明显升高:AECOPD治疗前组血清NF-κB(15.77±2.03)ng/ml、治疗后组(12.88±2.50)ng/ml(P0.05);正常对照组为(8.56±2.43)n g/ml(P0.05);(3)AECOPD时H_2S水平明显下降:AECOPD治疗前组血清H_2S(19.72±3.99)nmol/ml、治疗后组(24.37±7.32)nmol/ml(P0.05);正常对照组(38.17±4.63)nmol/ml(P0.05)。3.亚层分析:(1)根据GOLD肺功能分级示II级、III级、IV级ROS值分别为(521.35±57.71)IU/ml、(567.88±53.44)IU/ml、(658.96±34.80)IU/ml,呈逐步升高趋势(P0.05);NF-κB值分别为(15.16±2.30)ng/ml、(15.92±1.57)ng/ml、(16.62±1.91)ng/ml,呈逐步升高趋势;H_2S值分别为(22.20±3.22)nmol/ml、(19.73±3.38)nmol/ml、(15.28±1.65)n mol/ml,呈逐步下降趋势(P0.05);(2)根据是否合并HP示AECOPD合并HP组较AECO PD非合并HP组ROS明显升高(分别为(611.34±70.81)IU/ml、(543.89±64.12)IU/ml,P0.05);NF-κB明显升高(分别为(16.69±1.64)ng/ml、(15.20±2.05)ng/ml,P0.05);H_2S明显下降(分别为(17.51±3.57)nmol/ml、(21.09±3.04)nmol/ml,P0.05)。4.相关性分析:(1)血清H_2S与FEV1%预计值、Pa O2、6MWT呈正相关(r=0.605,0.759,0.755,P均0.05),与PASP、MMRC、WBC、GRA、CRP呈负相关(r=-0.436,-0.516,-0.261,-0.266,-0.268,P均0.05);血清ROS与FEV1%预计值、6MWT、Pa O2呈负相关(r=-0.698,-0.676,-0.896,P均0.05);与PASP、MMRC、WBC、GRA、CRP呈正相关(r=0.477,0.463,0.318,0.316,0.329,P均0.05);血清NF-κB与FEV1%预计值、P a O2呈负相关(r=-0.330,-0.344,P均0.05),与PASP、MMRC、WBC、GRA、CRP呈正相关(r=0.283,0.276,0.519,0.516,0.566,P均0.05)。5.AECOPD治疗前组血清H_2S与ROS、NF-κB呈负相关(r=-0.887,-0.281,P均0.05),血清ROS与NF-κB呈正相关(r=0.356,P均0.05)。结论1.内源性H_2S、ROS可能在COPD及COPD相关性PH的氧化应激机制中起重要作用。2.AECOPD时ROS可能通过NF-κB产生氧化应激损伤,而内源性H_2S可能通过抑制R OS及NF-κB活化而减轻其损伤。3.内源性H_2S、ROS与COPD的急性加重、病情的严重程度密切相关,可作为病情严重程度的评价指标。
[Abstract]:Objective To observe the changes of serum hydrogen sulfide (H_2S), reactive oxygen species (ROS) and nuclear factor kappa B (NF- kappa B) in patients with acute exacerbation of chronic obstructive pulmonary disease (AECOPD), and to explore its clinical significance. Methods 60 cases of AECOPD patients in the respiratory department of the Ningxia Hui Autonomous Region people's Hospital in December November 2015 (according to COPD global) were selected. GOLD classification standard [1], which according to the COPD airflow severity grade (GOLD): 25 patients with II, 21 cases of III, 14 cases of IV, according to the revised [2] diagnostic standard of the guideline >2013 for the diagnosis and treatment of chronic obstructive pulmonary disease issued by the Chinese Medical Association for respiratory diseases. The normal control group chose the same period in our hospital body. 60 healthy subjects were examined at the examination center, and the age, sex, body mass index, and smoking index were matched in the two groups. The group of AECOPD patients were divided into two groups before and after treatment. The definition of the post treatment group: 60 patients in the group were given the same routine treatment regimens such as oxygen inhalation, anti infection, antispasmodic antiasthmatic, and so on (excluding the use of vitamin drugs. According to the results of echocardiographic examination at the time of admission (pulmonary systolic pressure (PASP) 50mm Hg as pulmonary hypertension), COPD combined with pulmonary hypertension group and COPD non pulmonary hypertension group were set up. Before treatment, after treatment and normal control by enzyme linked immunosorbent assay (ELISA), AECOPD patients were treated with enzyme linked immunosorbent assay (ELISA). The levels of serum H_2S, ROS and NF- kappa B were compared with Pa CO2, Pa O2, the percentage of expected expiratory volume in the first second (FEV1% expected), PASP, six minute walk test (6MWT), improved respiratory difficulty score (MMRC), blood routine white blood cell count, neutrophils absolute value and hypersensitive reactive protein. Results there was no significant difference in sex, age, body mass index and smoking index between the 1. normal control group and the AECOPD group (P0.05). The FEV1/FVC of group AECOPD was significantly lower than that of the normal control group (P0.05).2.AECOPD treatment and the normal control group. The level of H_2S, ROS and NF- kappa B in the three groups of the normal control group were significantly increased (1) AECOPD when the ROS level increased. High: serum ROS (569.74 + 73.97) IU/ml before treatment and after treatment (396.93 + 83.40) IU/ml (P0.05), normal control group (285.01 + 68.89) IU/ml (P0.05), and (2) AECOPD, NF- kappa B level was significantly increased: AECOPD before treatment group (15.77 + 2.03), after treatment group (12.88 + 2.50); normal control group (8.56 + 2.43) (05) (3) the level of H_2S decreased significantly at AECOPD: the serum H_2S (19.72 + 3.99) nmol/ml before the AECOPD treatment group and the group (24.37 + 7.32) nmol/ml (P0.05) after treatment, and the normal control group (38.17 + 4.63) nmol/ml (P0.05).3. sublayer analysis: (1) according to GOLD lung function classification of II grade (521.35 + 57.71), (567.88 + 53.44), (567.88 + 53.44), (567.88 + 53.44), (567.88 + 53.44) + 34.80) IU/ml, showing a gradual increasing trend (P0.05); NF- kappa B values are (15.16 + 2.30) ng/ml, (15.92 + 1.57) ng/ml and (16.62 + 1.91) ng/ml, showing a gradual increase trend, H_2S values are (22.20 + 3.22) nmol/ml, (19.73 + 3.38) nmol/ml, (15.28 + 1.65) n mol/ml, showing a gradual downward trend. The ROS in the non combined HP group increased significantly (611.34 + 70.81) IU/ml, (543.89 + 64.12) IU/ml, P0.05), NF- kappa B increased significantly (16.69 + 1.64) ng/ml, (15.20 + 2.05) ng/ml, P0.05), and H_2S significantly decreased (17.51 + 3.57), respectively (21.09 + 3.04) Positive correlation (r=0.605,0.759,0.755, P 0.05), negative correlation with PASP, MMRC, WBC, GRA, CRP (r=-0.436, -0.516, -0.261, -0.266, -0.268, 0.05); Kappa B is negatively correlated with FEV1%, P a O2 (r=-0.330, -0.344, P are 0.05), and is positively correlated with PASP, MMRC, WBC, GRA, and GRA. When OS may play an important role in the oxidative stress mechanism of COPD and COPD related PH, ROS may produce oxidative stress damage through NF- kappa B, and endogenous H_2S may reduce its injury by inhibiting R OS and NF- kappa activation, which is closely related to the severity of the disease and the severity of the disease, and can be used as a serious condition. Evaluation index of degree.
【学位授予单位】：宁夏医科大学
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：R563.9

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