Association of gene polymorphisms of tumour necrosis factor-α and interleukin-13 with chronic obstructive pulmonary disease in Han nationality in Beijing

Background Genetic factors are believed to play a role in the individual susceptibility to chronic obstructive pulmonary disease (COPD). A single nucleotide polymorphism (SNP) of tumour necrosis factor-α (TNF-α)has been reported but inconsistent results may arise from different populations and phenotypes of COPD. There are only a few published studies of interleukin-13 (IL-13) SNPs on COPD. The SNPs of TNF-α and IL-13 have not been studied in the Chinese population. This research was conducted to study the frequencies of IL-13 gene promoter 1055 (IL-13-1055) and TNF-α gene-308 polymorphisms in the patients with COPD and to investigate the effect of those genetic polymorphisms on COPD in the Chinese population.Methods A cohort of COPD patients and age matched controls were recruited from an inpatient hospital service in Beijing. Venous blood was obtained and genomic DNA was extracted from peripheral blood monocytes using standard method. Genomic DNA was used as a template for amplification by polymerase chain reaction(PCR) to determine the polymorphism at -1055 in the length polymorphism (RFLP) was used to determine polymorphisms in the TNF-α gene-308 position. The products were investigated by sequence analysis also.Results One hundred and eleven COPD patients and 97 controls were studied. Seventy-five cases were current smokers in COPD patients and 36 were current smokers in controls. The frequencies of TT genotype in the IL-13 gene promoter region were 11.7% ( 13/111 ) in the COPD group and 13.4% (13/97) in the controls (P =0. 713). However, the OR value of TT genotype was significantly increased to 6.4 (95% CI 1.62 -25.39) in the smokers with COPD. TT genotype was also positively related to family history of COPD, OR =7. 7 (95% CI 1.37 -43.80). The frequencies of A allele in the TNF-α gene were 5.9% in COPD and 3. 1% in controls (P=0. 131 ). The OR value of A allele was 5.0 (95% CI 1.011 to 25. 059) in smokers with COPD.Conclusions There is no significant difference in the frequencies of the TT genotype of IL-13-1055 or the A allele of the TNF-α between Han Chinese patients with COPD versus control. Thus, it does not appear that these SNPs are independent factors in COPD for Han nationality in Beijing. However, these SNPs may increase the risk of COPD among smokers.     

Impact of genetic variation of tumor necrosis factor-α on gestational hypertension

Background The mechanisms responsible for the pathogeneses of gestational hypertension and preeclampsia are unclear. Tumor necrosis factor-1α （TNF-1α） is a pro-inflammatory Th1-type cytokine. TNFA gene is located in the human leukocyte antigen （HLA） class Ⅲ region of the major histocompatibility complex （MHC） on chromosome 6. The high TNF-1α mRNA expression may be associated with the TNF2 （A） allele, which is the polymorphism of TNF-1α at position - 308 in promoter region. This study assessed whether the TNF2 （A） allele at position -308 plays a role in the alteration of blood pressure （BP） and urinary protein excretion during pregnancy. Methods The original prospective cohort study comprised 1623 pregnant women from January 2000 to October 2001. The G/A polymorphism was done by restriction fragment length polymorphism （RFLP） analysis with Nco I enzyme. Results The distributions of the G/A polymorphism of TNF-1α in the promoter region at position -308 were wild-type 72.4% and variant 27.6%, respectively. The frequency of TNF2 （A） allele was approximately 0.15 for Caucasian pregnant women in the study. It was not significantly different in the distributions of genotypes and G/A allele frequencies among the three groups of pregnant women with gestational hypertension, preexisting hypertension and normal blood pressure （P〉0.05）. The maternal blood pressure in the third trimester was significantly higher in the group of women possessing the TNF2 （A） allele compared to homozygous for the TNF1 （G） allele （systolic BE P〈0.01 and diastolic BE P〈0.05）. The elevated blood pressure in the TNF2 （A） group was accompanied by higher urinary protein excretion in the third trimester （P〈0.05）. The blood pressure and urinary protein excretion did not change apparently between the two groups in the first and second trimesters （P〉0.05）. Conclusions Maternal TNF2 （A） allele of TNF-1α promoter region at position -308 could play a role in the alteration of blood pressures and/or enhancement of urinary protein excretion during pregnancy, and might play an important role in the development of both gestational hypertension and preeclampsia.     

Effects of morphine and fentanyl on tumor necrosis factor-α and interleukin-6 concentrations in human whole blood in vitro

Cytokines are essential for hematopoiesis and immune responses, and play a key role in the defense against infections. Lipopolysaccharide (LPS) is a potent inducer of the agents involved in the pathogenesis of inflammation responses. Tumor necrosis factor-α（TNF-α） and interleukin-6(IL-6) are two important and proinflammatory     

Variations of tumor necrosis factor-α, leptin and adiponectin in mid-trimester of gestational diabetes mellitus

Background Many cytokines have been found to increase the insulin resistance during pregnancy complicated by glucose metabolism disorder. This study aimed to investigate which comes first, the changes of some cytokines or the abnormal glucose metabolism.
Methods This nested case-control study was undertaken from January 2004 to March 2005. Twenty-two women with gestational diabetes mellitus （GDM）, 10 with gestational impaired glucose tolerance （GIGT）, and 20 healthy pregnant women were chosen from the women who had visited the antenatal clinics and had blood samples prospectively taken and kept during their visit. The levels of tumor necrosis factor-α （TNF-α）, leptin and adiponectin were determined. One-way ANOVA analysis and bivariate correlation analysis were used to assess the laboratory results and their relationship with body mass index （BMI）. Results Women with GDM have the highest values of TNF-α and leptin and the lowest value of adiponectin compared with those with GIGT and the healthy controls （P 〈0.01） at 14-20 weeks of gestation. This was also found when these women progressed to 24-32 weeks. The significantly increased levels of TNF-α and leptin and the decreased level of adiponectin were found at the different periods of gestation within the same group. Positive correlation was shown between the levels of TNF-α and leptin at the two periods of gestation with the BMI at 14-20 weeks, while adiponectin was negatively correlated （P 〈0.05）.
Conclusions The concentrations of TNF-α, leptin and adiponectin may change before the appearance of the abnormal glucose level during pregnancy. Further studies are required to verify the mechanism of this alteration and whether the three cytokines can be predictors for GDM at an early staqe of preqnancy.     

The roles of tumor necrosis factor-α gene polymorphisms in the pathogenesis of non-alcoholic fatty liver diseases

目的 探讨肿瘤坏死因子-α(TNF-α)单核苷酸多态性(SNP)与非酒精性脂肪性肝病(NAFLD)发病及病程进展的相关性.方法 在2005年对普通人群NAFLD流行病学调查的基础上进行队列追踪到2009年(中位数4年),其中696例愿意接受复查,每例再行问卷、体检、血生化和B超检查,应用PCR-RFLP方法检测TNF-α 3个位点:-238、-308和-857的SNP.结果 2005年NAFLD标化患病率为21.29%,至2009年显著升高达46.11%.Hardy-Weinberg检验-238位点基因频率未达到遗传平衡(P<0.05),故予剔除,而-308及-857位点纳入研究.NAFLD患者与正常对照者比较,TNF-α -857位点的基因型及等位基因频率差异均有统计学意义(P<0.05),等位基因T型者的发病危险率(RR)是正常对照者的1.463倍;而-308位点两者差异无统计学意义(P＞0.05).有序logistic回归分析显示,性别对病程无显著影响(P＞0.05),年龄影响显著(P<0.001);校正性别和年龄后,-857位点T/T基因型与病程进展呈正相关,其危险性(OR)是C/C型的8.65倍(P<0.001),而C/T型与C/C型比较差异无统计学意义(P=0.072);-308位点各基因型对病程均无显著影响(P＞0.05).结论 TNF-α -857位点C→T变异(而非-308位点)与NAFLD发病易感性及病程进展两者均呈正相关,T/T型增加疾病发生和进展的风险.     

Comparative research between Bai-hua Qian-hu, a Chinese traditional plant, and its active ingredient on nuclear factor-κB and tumor necrosis factor-α in isolated ischemia-reperfusion heart of rat

Ischemia-reperfusion (I/R) injury is a complicated pathophysiological process, which is involved in calcium overload, free radical production, metabolic abnormalities, and inflammatory reaction. With the development of modem molecular biology, the expression and regulation of gene in myocardial I/R injury arefocused on NF-κB.     

Inhibition of tumor necrosis factor-α reduces alveolar septal cell apoptosis in passive smoking rats

Background Recent studies have revealed that lung cell apoptosis plays an important role in pathogenesis of cigarette-induced chronic obstructive pulmonary disease （COPD）. Tumor necrosis factor alpha （TNF-α） is one of the most important cytokines which are involved in COPD. This study aimed at investigating the influence of its inhibitor, recombinant human necrosis factor-alpha receptor II：lgG Fc fusion protein （rhTNFR：Fc） on alveolar septal cell apoptosis in passive smoking rats. Methods Forty-eight rats were randomly divided into a normal control group, a passive smoking group, an rhTNFR：Fc intervention group and a sham intervention group. The passive smoking rats were treated by exposure to cigarette smoking daily for 80 days. After smoking for one month the rhTNFR：Fc intervention group was treated with rhTNFR：Fc by subcutaneous injection, the sham intervention group injected subcutaneously with a neutral preparation （normal saline 0.1 ml, manicol 0.8 ml, cane sugar 0.2 mg, Tris 0.024 mg as a control. Lung function was determined and the levels of TNF-a in serum and broncho-alveolar lavage fluid （BALF） were measured with enzyme-linked immunosorbnent assay （ELISA）. Lung tissue sections stained by hematoxylin and eosin （HE） were observed for study of morphological alternations. Mean linear intercept （MLI） and mean alveolar numbers （MAN） were measured and the terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling （TUNEL） method was carried out to determine the percentage of positive cells and distribution of apoptotic cells. Results Increased MLI and decreased MAN were found in the passive smoking group compared with both the normal control group and the rhTNFR：Fc intervention group （P〈0.05）. Forced expiratory volume in 0.3 second （FEVo.3）/forced vital capacity （FVC） and peak expiratory flow （PEF） were lower in the passive smoking group than that in the normal control group （P〈0.05）. Compared with the sham intervention group     

Expression and role of adrenomedullm and its receptor in patients with chronic obstructive pulmonary disease

Objective To investigate the expression and role of adrenomedullin (ADM) and adrenomedullin receptor (ADMR) in patients with chronic obstructive pulmonary disease (COPD).Methods Small pulmonary artery remodeling was observed using morphometric analysis. The expression of ADM and ADMR mRNA in lung tissue was calculated by in situ hybridization in 9 COPD cases. Cardiac catheterization was performed in 22 COPD cases to monitor changes of hemodynamic parameters and patients were divided into two groups based on mean pulmonary artery pressure (mPAP). The cases without pulmonary hypertension (PH) were placed in Group A (n =12) and those with PH were placed in Group B (n =10). The levels of pulmonary arterial plasma ADM were measured by radioimmunoassay. Blood gas analysis was also conducted.Results The ratio of vascular wall thickness to external diameter (MT%) and the ratio of vascular wall area to total area (MA%) were higher in patients with COPD ( P < 0. 01). In situ hybridization showed that ADM mRNA and     

慢性阻塞性肺疾病患者血清瘦素水平与营养不良的关系

目的：了解慢性阻塞性肺疾病（COPD）患者血清瘦素水平及其与营养不良和疾病严重度之间的关系。方法：采用放射免疫法测定90例稳定期COPD患者及48例健康对照者血清瘦素水平，并测量身高、体重、颈围、胸围、腹围及用力肺活量（FVC）和第一秒用力呼气容积（FEVI），计算体质指数及理想体重百分比。其中40倒COPD患者及25例健康对照者同时测定了血清白蛋白、淋巴细胞总数、24h尿肌酐含量及肌酐身高指数。分析血清瘦素水平与营养参数及肺功能指标的关系。结果：血清瘦素水平COPD组显著低于健康对照组（P〈0．01），COPD患者营养不良组显著低于非营养不良组（P〈0．01）；COPD血清瘦素水平与绝大多数营养参数及FEVI／FVC呈显著正相关（P〈0．01）。结论：COPD患者血清瘦素水平下降；病情越重，营养状况越差，血清瘦素水平亦越低。     

血清瘦素及肿瘤坏死因子-α在慢性阻塞性肺病男性患者营养不良形成中的作用

目的:观察血清瘦素在慢性阻塞性肺病(chronic obstructive pulmonary disease,COPD)患者营养不良发生中的作用,及其与肿瘤坏死因子-α(tumor necrosis factor-α,TNF-α)的关系. 方法:本试验纳入患者均为男性.47例COPD患者分为非营养不良组(COPD Ⅰ组)29例,营养不良组(COPDⅡ组)18 例.正常对照组34例.测定体重指数(body mass index,BMI)、理想体重百分比(percent ideal body weight,IBW%)、三头肌皮褶厚度(triceps skin-fold thickness,TSF)、上臂围(mid-upper arm circumference,MAC)、上臂肌围(mid-upper arm muscle circumference,MAMC)、血清瘦素、TNF-α浓度、血清前白蛋白(serum prealbumin,PA)、血清转铁蛋白(serum transferring,TF)、血清白蛋白(serum albumin,Alb)、总淋巴细胞计数(total lymphocytes count,TLC)、第1秒用力呼气容积占预计值百分比(forced expiratory volume in one second,FEV1)、最大口腔吸气压(maximal inspiration pressure,MIP)、最大口腔呼气压(maximal expiration pressure,MEP)等指标.分析各组间各项指标的差异及相关性.瘦素测定用放射免疫法,TNF-α测定用ELISA法.结果 :(1)COPDⅡ组血清瘦素的质量浓度[(4.07±3.42) μg/L]明显低于COPD Ⅰ组[(9.72±6.67) μg/L]及正常对照组[(8.21±5.41) μg/L],差异有统计学意义(P<0.05).(2)COPDⅡ组血清TNF-α的质量浓度[(8.03±3.37) ng/L]与COPD Ⅰ组[(7.25±2.08) ng/L]相比差异无统计学意义.(3)各组血清瘦素浓度与TNF-α均无显著相关性.结论:在合并营养不良的COPD患者中,血清瘦素仍维持正常的生理调节.在COPD患者的能量代谢调节过程中,血清TNF-α与血清瘦素之间不存在相关性.     

Expressions of tumor necrosis factor-converting enzyme and ErbB3 in rats with chronic obstructive pulmonary disease

Background Chronic obstructive pulmonary disease (COPD) is associated not only with airway inflammation characterized by mucin hypersecretion but also with systemic inflammation. Tumor necrosis factor alpha (TNF-α) is found to take part in systemic inflammation, and ErbB3 plays an important role in mucin hypersecretion of COPD. Since TNF-α converting enzyme (TACE) is involved in the activation of both TNF-α and ErbB3, we established rat models of COPD to investigate the expressions of TACE, TNF-α and ErbB3 and to explore the correlations among TACE,TNF-α and ErbB3 respectively. Methods Thirty Wistar male rats were randomly divided into COPD group (group C, n=10), saline solution parallel group (group P, n=8), and normal control group (group N, n=8). Group C was challenged with passive cigarette smoking and intratracheal instillation of lipopolysaccharide. Six weeks later pulmonary functions were tested, bronchoalveolar fluid and arterial blood gases were assayed, and histopathological evaluations were performed in turn. The expressions of TACE, TNF-α and ErbB3 in lungs of all rats were determined histochemically. Results The expressions of TACE, TNF-α and ErbB3 were significantly higher in group C than in group N (P&lt;0.01). The contents of TNF-α in serum (P&lt;0.01) and bronchoalveolar lavage fluid (BALF) (P&lt;0.01) were elevated more significantly in group C than in group N. A positive correlation existed between TACE and TNF-α (r=0.784, P&lt;0.01) and between TACE and ErbB3 (r=0.526, P&lt;0.01) respectively. Conclusions TNF-α and ErbB3 are involved in the pathogenesis of COPD. TACE contributes to the progress of COPD indirectly through the function of TNF-α and ErbB3.     

慢性阻塞性肺疾病患者血清CTRP-9 水平 及其临床意义

目的 探讨慢性阻塞性肺疾病（COPD）患者血清C1q 肿瘤坏死因子相关蛋白9（CTRP-9） 水平及其临床意义。方法 选取2016 年10 月—2017 年10 月罗定市人民医院就诊的90 例COPD 稳定期 患者作为观察组,另选取同期于该院体检的90 例健康居民作为对照组。分别采集两组血浆标本,应用酶联 免疫吸附试验法测定两组血清CTRP-9 水平,采用肺功能仪测量两组第1 秒用力呼气容积占预计值百分比 （FEV1%pred）,并分析两组评价指标的相关性。结果 观察组血清CTRP-9 水平高于对照组（P<0.05）;观 察组FEV1%pred 低于对照组（P <0.05）;Pearson 相关性分析结果显示,观察组血清CTRP-9 水平与患者肺 功能指标FEV1%pred 呈负相关（r =-0.803,P =0.004）。结论 CTRP-9 在COPD 患者血清中呈高表达,且 其表达水平与患者肺功能存在相关性。     

慢性阻塞性肺疾病患者血清瘦素水平与炎性反应相关性

目的 探讨慢性阻塞性肺疾病(COPD)患者血清瘦素水平变化及其与炎性反应的关系,了解瘦素在COPD患者炎症反应过程中的作用及其意义.方法 选择COPD患者共58例,COPD急性加重期(Ⅰ组)30例,COPD缓解期(Ⅱ组)28例,正常对照组28例.测定和计算各组的多项营养指标,包括身高、体重、体重指数(BMI)、理想体重百分比(NM%)、体脂百分比(fat%).用酶联免疫吸附试验法(ELISA)测定58例COPD患者和28例正常人的血清瘦素、肿瘤坏死因子-α(TNF-α)、白细胞介素-8(IL-8)、超敏C-反应蛋白(hs-CRP)水平及肺功能,分析瘦素与各项参数的相关性.结果 ①COPD患者的各营养指标:BMI、NM%、fat%均显著低于正常对照组(P<0.01).②COPD I组血清瘦素、TNF-α、IL-8、hs-CRP均显著高于正常组与COPDⅡ组(P<0.01);COPDⅡ组血清瘦素低于正常组(P<0.01),TNF-α、IL-8、hs -CRP高于对照组(P<0.01);③COPD患者的瘦素含量与BMI、NM%、fat%、TNF-α、IL-8、hs -CRP水平显著正相关.结论 血清瘦素在COPD急性加重期明显高于缓解期,并与营养参数、TNF-α、IL-8、hs -CRP呈显著正相关,提示瘦素可能与COPD的疾病本身和全身炎症反应有关,可作为COPD急性加重期的炎症标志物. Abstract： Objective To investigate the expression and significance of serum leptin in patients with chronic obstructive pulmonary disease(COPD). Methods Thirty COPD patients in acute exacerbations phase (group I), 28 COPD patients in stationary phase(group Ⅱ) and 28 healthy controls were studied. Body height, body mass,body mass index (BMI), percentage of normal body mass (NM%), percentage of body fat(fat%) were determined.The serum leptin、TNF-α、IL-8、hs-CRP levels were examined by ELISA. The correlation between leptin and other parameters was analysed. Results ①BMI,NM% fat% in COPD patients significantly lower than those in healthy controls (P<0.01). ②Serum leptin、TNF-α、IL-8、hs-CRP level was significantly higher in group I than that in healthy controls and in group II (P<0.01); Serum leptin level was significantly lower in group II than that in healthy controls (P<0.01); Serum TNF-α、IL-8、hs-CRP level was higher in healthy controls (P<0.01). ③The leptin level was associated positively with BMI,NM%, fat%. TNF-α、IL-8、hs-CRP level of COPD. Conclusions The leptin level of COPD in acute is higher than that in stationary, and the levels were correlated to nutritional parameters,TNF-α,IL-8,hs-CRP.The result suggests that leptin may play a role in systemic inflamination of COPD, the leptin is an inflaming mark of the actue exacerbation phase in patients with COPD.     

血清斯钙素⁃1在稳定期慢性阻塞性肺病中的表达及意义

目的：探讨斯钙素?1（stanniocalcin?1,STC1）在稳定期慢性阻塞性肺病（chronic obstructive pulmonary disease,COPD）患者血清中的表达及意义。方法：收集55例稳定期COPD患者,根据肺功能和问卷评分进行相应分组,且以24例健康者作为对照。采用酶联免疫吸附法（ELISA）测定各研究对象的血清斯钙素?1表达情况,进行相关分析。结果：①与健康对照组相比,稳定期COPD患者血清斯钙素?1表达水平明显降低（P < 0.05）。②血清斯钙素?1在初筛COPD上具有一定价值（P=0.025,AUC=0.659）,最佳阈值为1 350 pg/mL（敏感度81.82%;特异度50.00%）。③血清斯钙素?1与稳定期COPD患者病情严重程度［包括GOLD分级、慢阻肺评估测试（COPD assessment test,CAT）评分、ABCD分组、肺功能］无明显相关性。结论：血清斯钙素?1在COPD中显著降低,可能对于COPD的诊治具有一定临床意义。     

瘦素在慢性阻塞性肺疾病患者诱导痰中的变化及意义

目的明确瘦素（leptin）在慢性阻塞性肺疾病（COPD）患者诱导痰中的表达情况，痰中瘦素与炎症因子肿瘤坏死因子-α（TNF-α）、C反应蛋白（CRP）的关系。方法用酶联免疫吸附试验双抗体夹心法及放射免疫法测定20例中度COPD患者诱导痰中瘦素、TNF-α、CRP水平，同时检测血清中瘦素水平，分析相关性。结果COPD患者诱导痰中瘦素表达水平升高，与对照组比较差异有统计学意义（p〈0．05）。COPD患者诱导痰中瘦素水平与TNF-α（f=0．785，P〈0．05）、CRP（f=0．860，P〈0．05）呈显著正相关（P〈0．05）而血浆中的瘦素与诱导痰中瘦素水平呈负相关（r=-0．679，P〈0．05）。结论中度COPD患者诱导痰中瘦素表达水平升高，其与炎症因子TNF-α、CRP的关系提示瘦素可能参与COPD的气道局部炎症反应。     

慢性阻塞性肺疾病患者血清中MMP-9和TNF-α的检测及其相关研究

目的研究慢性阻塞性肺疾病（COPD）患者急性加重期和稳定期血清中MMP-9和TNF-α变化的临床意义。方法采用ELISA方法，分别检测25例患者在COPD急性加重期、稳定期及20例正常人血清MMP-9和TNF-α水平，并进行比较。结果COPD急性加重期TNF-α水平高于稳定期、正常人，而后两组TNF-α水平相近；但三组MMP-9水平相近。结论TNF-α参与了COPD的炎症过程，其血清水平有助于对COPD急性加重期进行检测。MMP-9在COPD急性加重期和稳定期都有高水平表达，尚待进一步观测。