內(nèi)源性硫化氫及活性氧在慢性阻塞性肺疾病中的作用
發(fā)布時(shí)間:2018-05-30 19:31
本文選題:慢性阻塞性肺疾病 + 內(nèi)源性硫化氫; 參考:《寧夏醫(yī)科大學(xué)》2017年碩士論文
【摘要】:目的觀察慢性阻塞性肺疾病急性加重期(AECOPD)患者血清硫化氫(H_2S)、活性氧(ROS)和核轉(zhuǎn)錄因子-κB(NF-κB)水平變化,并探討其臨床意義。方法選擇2015年11月-2016年12月就診于寧夏回族自治區(qū)人民醫(yī)院呼吸內(nèi)科的AECOPD患者60例(根據(jù)COPD全球創(chuàng)議(GOLD)分級(jí)標(biāo)準(zhǔn)[1],其中根據(jù)COPD氣流受限嚴(yán)重程度分級(jí)(GOLD):II級(jí)患者25例,III級(jí)患者21例,IV級(jí)患者14例),根據(jù)中華醫(yī)學(xué)會(huì)呼吸病學(xué)分會(huì)頒布的《慢性阻塞性肺疾病診治指南》2013年修訂版[2]診斷標(biāo)準(zhǔn)入組。正常對(duì)照組選擇同期在我院體檢中心體檢的健康者60例,兩組間年齡、性別、體重指數(shù)、吸煙指數(shù)指標(biāo)匹配。將入組的AECOPD患者再分為治療前和治療后兩組。治療后組的定義:入組的60例AECOPD患者給予吸氧、抗感染、解痙平喘等一致的常規(guī)治療方案(不包括使用維生素類藥物),癥狀緩解達(dá)到出院標(biāo)準(zhǔn)時(shí)為治療后組。根據(jù)入院當(dāng)時(shí)超聲心動(dòng)圖檢查的結(jié)果(肺動(dòng)脈收縮壓(PASP)50mm Hg為肺動(dòng)脈高壓),設(shè)立COPD合并肺動(dòng)脈高壓組及COPD非肺動(dòng)脈高壓組。使用酶聯(lián)免疫法(ELISA)測(cè)定AECOPD患者治療前、治療后及正常對(duì)照組血清H_2S、ROS和NF-κB的水平,并與Pa CO2、Pa O2、第一秒用力呼氣容積占預(yù)計(jì)值百分比(FEV1%預(yù)計(jì)值)、PASP、六分鐘步行實(shí)驗(yàn)(6MWT)、改進(jìn)的呼吸困難評(píng)分(MMRC)、血常規(guī)中白細(xì)胞計(jì)數(shù)(WBC)、中性粒細(xì)胞絕對(duì)值(GRA)及超敏C反應(yīng)蛋白(CRP)等進(jìn)行相關(guān)性分析。結(jié)果1.正常對(duì)照組與AECOPD組之間在性別、年齡、體重指數(shù)及吸煙指數(shù)上統(tǒng)計(jì)學(xué)均無(wú)顯著性差異(P0.05),AECOPD組FEV1/FVC明顯低于正常對(duì)照組(P0.05)。2.AECOPD治療前后及正常對(duì)照組三組的血清H_2S、ROS和NF-κB的水平變化:(1)AECOPD時(shí)ROS水平明顯升高:AECOPD治療前組血清ROS(569.74±73.97)IU/ml、治療后組(396.93±83.40)IU/ml(P0.05);正常對(duì)照組(285.01±68.89)IU/ml(P0.05);(2)AECOPD時(shí)NF-κB水平明顯升高:AECOPD治療前組血清NF-κB(15.77±2.03)ng/ml、治療后組(12.88±2.50)ng/ml(P0.05);正常對(duì)照組為(8.56±2.43)n g/ml(P0.05);(3)AECOPD時(shí)H_2S水平明顯下降:AECOPD治療前組血清H_2S(19.72±3.99)nmol/ml、治療后組(24.37±7.32)nmol/ml(P0.05);正常對(duì)照組(38.17±4.63)nmol/ml(P0.05)。3.亞層分析:(1)根據(jù)GOLD肺功能分級(jí)示II級(jí)、III級(jí)、IV級(jí)ROS值分別為(521.35±57.71)IU/ml、(567.88±53.44)IU/ml、(658.96±34.80)IU/ml,呈逐步升高趨勢(shì)(P0.05);NF-κB值分別為(15.16±2.30)ng/ml、(15.92±1.57)ng/ml、(16.62±1.91)ng/ml,呈逐步升高趨勢(shì);H_2S值分別為(22.20±3.22)nmol/ml、(19.73±3.38)nmol/ml、(15.28±1.65)n mol/ml,呈逐步下降趨勢(shì)(P0.05);(2)根據(jù)是否合并HP示AECOPD合并HP組較AECO PD非合并HP組ROS明顯升高(分別為(611.34±70.81)IU/ml、(543.89±64.12)IU/ml,P0.05);NF-κB明顯升高(分別為(16.69±1.64)ng/ml、(15.20±2.05)ng/ml,P0.05);H_2S明顯下降(分別為(17.51±3.57)nmol/ml、(21.09±3.04)nmol/ml,P0.05)。4.相關(guān)性分析:(1)血清H_2S與FEV1%預(yù)計(jì)值、Pa O2、6MWT呈正相關(guān)(r=0.605,0.759,0.755,P均0.05),與PASP、MMRC、WBC、GRA、CRP呈負(fù)相關(guān)(r=-0.436,-0.516,-0.261,-0.266,-0.268,P均0.05);血清ROS與FEV1%預(yù)計(jì)值、6MWT、Pa O2呈負(fù)相關(guān)(r=-0.698,-0.676,-0.896,P均0.05);與PASP、MMRC、WBC、GRA、CRP呈正相關(guān)(r=0.477,0.463,0.318,0.316,0.329,P均0.05);血清NF-κB與FEV1%預(yù)計(jì)值、P a O2呈負(fù)相關(guān)(r=-0.330,-0.344,P均0.05),與PASP、MMRC、WBC、GRA、CRP呈正相關(guān)(r=0.283,0.276,0.519,0.516,0.566,P均0.05)。5.AECOPD治療前組血清H_2S與ROS、NF-κB呈負(fù)相關(guān)(r=-0.887,-0.281,P均0.05),血清ROS與NF-κB呈正相關(guān)(r=0.356,P均0.05)。結(jié)論1.內(nèi)源性H_2S、ROS可能在COPD及COPD相關(guān)性PH的氧化應(yīng)激機(jī)制中起重要作用。2.AECOPD時(shí)ROS可能通過NF-κB產(chǎn)生氧化應(yīng)激損傷,而內(nèi)源性H_2S可能通過抑制R OS及NF-κB活化而減輕其損傷。3.內(nèi)源性H_2S、ROS與COPD的急性加重、病情的嚴(yán)重程度密切相關(guān),可作為病情嚴(yán)重程度的評(píng)價(jià)指標(biāo)。
[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.
【學(xué)位授予單位】:寧夏醫(yī)科大學(xué)
【學(xué)位級(jí)別】:碩士
【學(xué)位授予年份】:2017
【分類號(hào)】:R563.9
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