Research progress on prevention and treatment of Helicobacter pylori neutrophil-activating protein related diseases
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摘要:
幽门螺杆菌(H. pylori)中性粒细胞激活蛋白(HP-NAP)是新近发现的H. pylori的主要毒力因子之一, 几乎所有H. pylori菌株都有表达。HP-NAP被激活后，可刺激中性粒细胞、单核细胞、树突状细胞、肥大细胞和淋巴细胞，参与炎症的发展和组织损伤。本文对HP-NAP在相关疾病的预防、治疗中的最新研究进展予以综述。
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关键词:
- 幽门螺杆菌中性粒细胞激活蛋白 /
- 菌株 /
- 中性粒细胞 /
- 疫苗
Abstract:Helicobacter pylori (H. pylori) neutrophil-activating protein (HP-NAP) is one of the newly discovered main virulence factors of H. pylori, and is expressed in almost all strains of H. pylori. After being activated, HP-NAP can participate in the development of inflammation and tissue damage by stimulating neutrophils, monocytes, dendritic cells, mast cells and lymphocytes. This paper reviewed the latest research progress of HP-NAP in the prevention and treatment of related diseases.
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Keywords:
- Helicobacter pylori neutrophil-activating protein /
- strain /
- neutrophils /
- vaccines
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慢性阻塞性肺疾病急性加重期(AECOPD)患者病情较为严重，体内多种炎性细胞被激活，大量释放出白介素-8(IL-8)、肿瘤坏死因子-α(TNF-α)等多种炎症因子，导致机体慢性炎症及气道炎症反应加重[1-3]。本研究探讨抗血小板治疗AECOPD患者的疗效，现报告如下。
1. 资料与方法
1.1 一般资料
选取本院2015年5月—2018年5月收治的AECOPD患者80例，随机分为观察组与对照组，每组40例。对照组男22例，女18例，年龄60~78岁，平均(68.20±3.40)岁; 观察组男21例，女19例，年龄60~79岁，平均(68.40±3.30)岁。所有患者均符合慢性阻塞性肺疾病(COPD)诊断指南中的相关诊断标准[4-5], 且伴有呼吸系统恶化症状。排除标准：伴有恶性肿瘤及血液系统疾病者；伴有糖尿病、严重肝肾功能不全者；伴有免疫系统疾病者；近1个月内有手术及出血情况者；近2周内使用过抗血小板及抗凝药物治疗者。
1.2 方法
对照组患者给予常规方法治疗，包含支气管扩张剂、低流量吸氧、祛痰剂及抗生素抗感染等治疗。观察组在对照组基础上给予100 mg阿司匹林肠溶片(德国拜耳医药保健有限公司，批准文号J20130078)口服治疗, 1次/d。2组患者均治疗14 d。
1.3 观察指标
① 检测并比较2组患者治疗前后IL-8、TNF-α及超敏C反应蛋白(hs-CRP)等炎症因子水平。检测方法: 清晨抽取患者空腹静脉血，置入离心机内，以3 000转/min离心10 min, 取上层血清保存于-80 ℃环境中，采用酶联免疫吸附法检测各项指标。②检测并比较2组患者治疗前后用力肺活量(FVC)、第1秒用力呼气容积(FEV1)、第1秒用力呼气容积与用力肺活量比值(FEV1/FVC)等指标。检测方法: 采用Profiler肺功能测试系统(美国麦加菲公司)检测FVC、FEV1、FEV1/FVC等指标。③采用改良英国医学研究理事会[6-9]呼吸困难指数(mMRC)对呼吸困难进行评价。1级: 患者爬小坡或快走时出现呼吸困难，计1分; 2级: 患者行走一段距离或因气促而行走速度缓慢需停下休息，计2分; 3级: 患者步行几分钟或平路行走100 m需停下喘气，计3分; 4级: 患者日常穿衣脱衣出现呼吸困难症状或呼吸困难明显而无法外出，计4分。按照上述标准对2组患者进行评分，计算并比较mMRC。
1.4 统计学分析
采用SPSS 19.0统计软件处理数据，计量资料采用均数±标准差表示，比较行t检验, P＜0.05为差异有统计学意义。
2. 结果
2.1 2组治疗前后炎症因子水平对比
治疗前, 2组IL-8、hs-CRP及TNF-α水平比较无显著差异(P>0.05); 治疗后, 2组各指标水平均显著低于治疗前(P＜0.05), 且观察组各指标水平均显著低于对照组(P＜0.05), 见表 1。
表 1 2组治疗前后炎症因子水平比较(x±s)组别 时点 IL-8/(pg/mL) hs-CRP/(mg/L) TNF-α/(pg/mL) 观察组(n=40) 治疗前 34.62±8.07 23.83±1.31 65.63±8.92 治疗后 16.41±5.24*# 12.55±0.51*# 34.41±6.12*# 对照组(n=40) 治疗前 33.97±8.11 24.02±1.29 64.87±8.97 治疗后 21.63±6.52* 17.42±0.86* 45.83±7.57* IL-8: 白介素-8; TNF-α: 肿瘤坏死因子-α; hs-CRP: 超敏C反应蛋白。与治疗前比较, *P＜0.05; 与对照组比较, #P＜0.05。 2.2 2组治疗前后肺功能及呼吸功能指标比较
治疗前, 2组FVC、FEV1、FEV1/FVC及mMRC等指标比较无显著差异(P>0.05); 治疗后, 2组FVC、FEV1、FEV1/FVC指标水平均显著高于治疗前, mMRC水平显著低于治疗前(P＜0.05), 且观察组治疗后FVC、FEV1、FEV1/FVC指标水平均显著高于对照组, mMRC水平显著低于对照组(P＜0.05), 见表 2。
表 2 2组治疗前后肺功能及呼吸功能指标比较(x±s)组别 时点 FVC/L FEV1/L (FEV1/FVC)/% mMRC/分 观察组(n=40) 治疗前 2.03±0.19 1.31±0.26 50.36±3.52 1.83±0.32 治疗后 2.22±0.37*# 1.52±0.57*# 55.89±5.28*# 1.31±0.18*# 对照组(n=40) 治疗前 2.02±0.21 1.34±0.25 50.29±3.56 1.84±0.36 治疗后 2.14±0.29* 1.42±0.36* 52.87±4.27* 1.65±0.26* FVC: 用力肺活量; FEV1: 第1秒用力呼气容积; FEV1/FVC: 第1秒用力呼气容积与用力肺活量比值; mMRC: 呼吸困难指数。与治疗前比较, *P＜0.05; 与对照组比较, #P＜0.05。 3. 讨论
慢性阻塞性肺疾病属于常见的慢性呼吸系统疾病，具有发病率高、致死率高等特征，在该病发展过程中，炎症反应有重要作用[10-11]。张晓宁等[12]研究表明, AECOPD患者血小板活化明显。研究[13]显示，采用抗血小板药物治疗AECOPD患者能够显著降低病死率，在炎症及调控中性粒细胞生物学功能中，血小板有驱动作用。对于COPD患者而言，因其气道存在持续慢性炎症，血小板在急性加重期炎症反应中有驱动作用[14]。因此，在AECOPD患者治疗中，抗血小板治疗是有效的方法之一。
本研究观察组在常规治疗的基础上应用抗血小板药物辅助治疗，结果显示观察组患者IL-8、hs-CRP及TNF-α等炎症因子水平显著低于对照组(P＜0.05), 表明抗血小板药物在改善AECOPD患者炎症反应方面具有较好的效果。在肺功能及呼吸功能方面，观察组治疗后改善效果也显著优于对照组(P＜0.05)。抗血小板治疗在AECOPD患者中的优势可能与以下因素有关: ① AECOPD患者因慢性缺氧导致血液黏稠度增高、继发性红细胞增多及血液流速减慢，对血小板活化有刺激作用[15]; ②肺泡破裂在AECOPD患者中多发，对血小板活化也有刺激作用[16]; ③急性感染期患者体内内毒素对凝血酶有激活作用，单核巨噬细胞可将大量血小板因子释放出来，血小板活化加剧。血小板活化后，可释放血栓素A2、血小板激活因子、血小板源性生长因子、血小板因子4及氧自由基等炎性介质，上述各种释放因子均会不同程度地加重组织损伤，进一步加重机体炎症反应，导致COPD症状加重[17-18]。因此，抗血小板药物的使用对释放的血小板炎性因子有抑制效果，能减轻机体炎症反应，缓解AECOPD患者病情。
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