Research progress on roles of bile acids and its receptors in pathogenesis of non-alcoholic fatty liver disease and pharmacological treatment
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摘要:
非酒精性脂肪性肝病(NAFLD)是以肝细胞内脂质蓄积为主要特征的肝脏代谢紊乱疾病，已成为全球范围内慢性肝病的主要病因。20%~30%的NAFLD会进展为非酒精性脂肪性肝炎(NASH), NASH的发展与多种代谢紊乱密切相关。胆汁酸及其受体功能在NASH的发病机制中起着重要作用，胆汁酸受体是治疗NASH重要的靶点。本文对胆汁酸及其受体在NAFLD和NASH发展中的作用，特别是关于法尼醇X受体(FXR)在不同组织(包括肝脏和肠道)中的功能的研究予以综述，介绍基于胆汁酸及其受体的NASH治疗药物的研究进展。
Abstract:Non-alcoholic fatty liver disease (NAFLD) is a liver metabolic disorder characterized by lipid accumulation in liver cells, and it has become the main cause of chronic liver disease worldwide. 20% to 30% of patients with NAFLD were able to progress to non-alcoholic steatohepatitis (NASH), and the development of NASH is closely related to various metabolic disorders. Bile acids and its receptor function play important roles in the pathogenesis of NASH, and bile acid receptors are the important targets for the treatment of NASH. This article reviewed the roles of bile acids and their receptors in the development of NAFLD and NASH, especially the functional research of farnesol X receptors (FXR) in different tissues (including liver and intestine), and introduced the research progress of NASH therapeutic drugs based on bile acids and their receptors.
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呼吸系统疾病是儿科疾病中较为常见的感染性疾病，临床表现为呼吸困难、咳嗽等，严重者会因呼吸衰竭而死亡[1]。据世界卫生组织(WHO)统计，呼吸道感染是造成5岁以下儿童死亡的主要原因[2-3]。目前对于小儿呼吸系统疾病的治疗，临床上主要采用雾化吸入的方式，可以有效防止支气管痉挛，同时保证呼吸通畅[4]。通过雾化吸入治疗的药物直接作用于呼吸道，局部靶向药物浓度高，起效快，无创伤，且使用方便，不需要患儿刻意配合，护理人员较容易掌握[5]。如何采取有效的护理干预措施，提升小儿呼吸系统疾病吸入治疗的临床效果、缩短患儿住院时间、改善预后是目前临床亟待解决的问题。集束化护理是基于循证依据，集合一系列护理措施形成的护理方案[6]。本研究选取60例呼吸系统疾病患儿为研究对象，旨在探讨集束化护理模式与常规护理模式所产生的临床成效差异，现报告如下。
1. 资料与方法
1.1 一般资料
选取2017年2月—2018年3月本院收治的60例呼吸系统疾病患儿为研究对象，男35例，女25例，年龄1个月~3岁。纳入标准: 经确诊均为小儿呼吸系统疾病，均有发热、咳嗽、咽痛、肺部啰音等临床征状，均采用雾化吸入治疗方法，本研究获得患儿家长知情并同意。排除标准: 重要器官严重疾病患者(含心、肝、肾等); 依从性差; 不能配合治疗与护理措施者; 不愿签署研究知情同意书者。将患者随机分为对照组和观察组各30例。对照组男17例，女13例; 年龄2个月~3岁，平均年龄(1.30±0.57)岁，上呼吸道感染12例，小儿肺炎9例，感染性咽炎6例，支气管哮喘3例。观察组男18例，女12例; 年龄1个月~3岁，平均年龄(1.53±0.48)岁，上呼吸道感染11例，小儿肺炎9例，感染性咽炎6例，支气管哮喘4例。2组在一般资料无显著差异(P>0.05), 具有可比性。
1.2 方法
1.2.1 对照组
入院后给予抗病毒药物和抗生素药物治疗，将药液注入雾化器储罐中，采用药物的雾化吸入治疗方式。对照组给予常规护理。
1.2.2 观察组
在常规护理的基础上进行集束化护理干预。⑴成立集束化护理小组: 由护士长、护理组长和优秀护士组成。负责制定集束化护理计划和措施细则，制定组员职责，改进护理质量。⑵加强病房管理：制定规范的病房管理制度，病房内每天进行消毒，定期检测空气细菌培养指数，严格室内温度控制在22~24 ℃, 湿度保持在25%~40%; 并每天开窗通风2次，每次20 min。⑶雾化吸入管理: ①雾化吸入治疗前，向患儿家长详细解释雾化吸入治疗的使用方法和注意事项，并积极寻求患儿家长的配合。②根据患儿的具体情况，调节雾化吸入量。用量过多会导致患儿出现供养不足和呼吸困难等症状，用量过少又会影响治疗效果。③根据医嘱明确患儿的雾化时间，一般每天进行2次，每次间隔时间在4 h以上，且单次吸入时间不可超过15 min。④进行雾化操作时，因患儿年龄较小，应该让患儿家长坐着抱好，取坐位或半卧位，并保持病房内通风良好和空气清新。⑤雾化过程中，密切关注患儿各项体征，检查雾化是否耐受，并评估和观察不良反应，以便及时通知医生进行处理。⑥完成雾化吸入后，需要对患儿口鼻部残留药物进行清理。⑷心理干预: 在治疗过程中患儿可能出现害怕等不良情绪，或者对治疗有抵触排斥心理，护理人员采用转移患儿注意力的方法安抚患儿，稳定患儿的情绪，同时采用音乐放松或家长陪护可改善患儿的恐惧心理，帮助其积极配合治疗。⑸饮食护理: 饮食以易消化和清淡为主，少食多餐，并注意营养补充，增加饮水量。⑹健康教育: 对患儿家长进行定期健康教育，帮助了解小儿呼吸系统疾病相关知识、发病机制、治疗方式和护理手段，叮嘱做好患儿的保暖工作和日常保健方法。
1.3 评价方法
① 临床效果评估：痊愈，患儿经治疗护理之后，各项临床症状都基本消失，各项体征和功能恢复正常；有效，患儿经治疗护理之后，各项临床症状在一定程度上得以好转，各项体征和功能基本恢复正常，偶有咳嗽、喘息等轻微症状；无效，患儿经治疗护理之后，各项临床症状未见改善，或有加重趋势。治疗总有效率=(痊愈+有效)/本组总例数×100%。②观察2组临床症状缓解时间和住院时间。③对患儿家长进行问卷调查，采用自制满意度量表对护理效果进行满意度评价，该表总分100分，包括服务态度、护理告知、职业道德和医疗环境，各25分。量表评分分为不满意、一般、非常满意。患儿家长满意度=(非常满意+一般)/本组总例数×100%。
1.4 统计学方法
采用SPSS 25.0进行数据分析，计数资料用[n(%)]表示，计量资料采用(x±s)表示，并利用计算机和人工对数据进行核查。组间数据比较采用χ2及t检验, P < 0.05为差异有统计学意义。
2. 结果
2.1 2组的临床疗效比较
对照组患儿痊愈7例，有效15例，无效8例，临床疗效为73.33%(22/30); 观察组患儿痊愈12例，有效16例，无效2例，临床疗效为93.33%(28/30), 观察组经集束化护理干预后的临床疗效显著较高(P < 0.05)。
2.2 2组的临床症状缓解时间和住院时间比较
观察组患儿各项临床症状(发热、咳嗽、肺部啰音)缓解时间较对照组显著缩短(P < 0.05); 观察组患儿平均住院时间为(13.54±3.09) d, 对照组为(15.95±3.76) d, 观察组显著短于对照组(P < 0.05), 见表 1。
表 1 2组临床症状缓解时间和住院时间比较(x±s)d 组别 发热缓解时间 咳嗽缓解时间 肺部啰音缓解时间 住院时间 对照组(n=30) 3.35±1.60 4.77±1.79 6.85±1.63 15.95±3.76 观察组(n=30) 2.47±1.24* 3.65±1.56* 6.04±1.41* 13.54±3.09* 与对照组比较, *P < 0.05。 2.3 2组患儿家长满意度比较
观察组经集束化护理干预后的家长满意度显著高于对照组(P < 0.05), 见表 2。
表 2 2组患儿家长满意度比较组别 非常满意 一般 不满意 满意度/% 对照组(n=30) 10 15 5 83.33 观察组(n=30) 18 12 0 100.00* 与对照组比较, *P < 0.05。 3. 讨论
小儿呼吸系统疾病好发于冬季和早春季节，临床表现为全身乏力、发热、咳嗽等，严重影响患儿的正常生活[7-8]。近年来空气污染严重，小儿呼吸系统疾病的发病率有升高趋势[9]。调查[10]显示，中国小儿呼吸系统疾病患儿占住院儿童总人数的25.8%~55.6%, 且2岁以下幼儿最为多见。因而，对小儿呼吸系统疾病的治疗和护理值得关注。雾化吸入治疗是较为常见的小儿呼吸系统疾病治疗方法，其原理是采用雾化装置将药液吹散并形成微小的雾粒，并在空气中悬浮形成气雾，然后经患者口鼻吸入直达病灶，最终促进疾病治愈，具有局部药物浓度高、安全性好、毒副作用小、操作简便等优点[11]。但婴幼儿由于不能主动配合治疗，因此护理工作具有重要意义。随着循证医学的发展，集束化护理应用于循证实践，并作为客观的医学临床研究证据，以制订各项护理干预措施，每个元素通过集合共同实施可提高护理效果[6]。
结果表明，本研究采用集束化护理干预呼吸系统疾病患儿的吸入治疗，并对临床疗效进行分析，对照组的临床总有效率为73.33%, 观察组经集束化护理干预后的临床疗效为93.33%, 与文献报道[12]相吻合，表明集束化护理干预能提高患儿吸入治疗的效果。集束化护理干预的护理人员均掌握全面的雾化吸入知识，通过向患儿家属进行健康宣教，提高家长对疾病的认知水平和护理事项的配合度。研究[13]指出，病房环境不舒适、患儿的紧张情绪等均会影响呼吸系统疾病患者的治疗依从性和临床疗效，而本研究采取的集束化护理干预，通过加强病房管理，营造舒适干净的病房环境，可提高患儿和家长的心情愉悦度，减少患儿对治疗和护理的排斥心理，从而提高临床配合度，促进护理工作顺利进行。报道[14]指出，治疗之前根据医嘱和患儿具体情况，调节雾化药的温度、药物浓度和治疗时间等，选择合适尺寸的口含器，并耐心与患儿和家长沟通，让患儿配合治疗，可减少患儿的不适感，提高患儿配合度，从而提升治疗效果。本研究中，观察组的各项住院时间和临床症状缓解时间均显著短于对照组，与报道[15]一致，说明集束化护理干预能加快患儿发热、咳嗽和肺部啰音等临床症状的缓解，并缩短患儿的住院时间。分析其原因可能在于，集束化护理干预会密切关注患儿日常生活中的护理，保证患儿有较为充足的睡眠时间，加强患儿的饮食管理，以高营养、高蛋白为原则指导患儿的日常饮食，在满足患儿日常需要的同时，进一步加强免疫力，帮助患儿机体功能快速恢复，达到缩短患儿住院时间的目的。另外，从家长满意度上看，集束化护理干预从患者的角度出发，提供综合全面和有针对性的医疗干预措施，可提高患者全方位的舒适感，可促进与家长和患儿的心理交流，帮助建立融洽的护患关系，加强患儿的安全感和治疗依从性，提升了临床疗效，进一步提高患儿家长的满意度。
综上所述，应用集束化护理干预对小儿呼吸系统疾病的吸入治疗，可优化疗效并缩短患儿住院时间，提高家长满意度。
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