脂联素对重症急性胰腺炎的保护作用及其机制

目的:探讨脂联素在重症急性胰腺炎发生发展中的重要作用及其相关机制。方法:60只C57小鼠随机分为脂联素预处理组、脂联素治疗组和对照组,每组20只。以雨蛙肽连续腹腔注射建立重症急性胰腺炎模型,采用病理评分及检测血清淀粉酶、脂肪酶评估胰腺炎症程度,检测血清TNF-α、IL-6、IL-1β水平以评估全身炎症状态,确定脂联素对重症急性胰腺炎的重要作用。对胰腺腺泡细胞AR42J使用脂联素预处理后建立胰腺炎模型,检测通路蛋白NF-κB和促炎因子TNF-α的表达水平,研究脂联素的可能作用通路。结果:建模后,脂联素预处理组和脂联素治疗组小鼠的病理评分显著低于对照组,且血清淀粉酶、脂肪酶及血清TNF-α、IL-6、IL-1β水平也均显著低于对照组(P0.05)。脂联素预处理后AR42J细胞表达NF-κB及TNF-α水平显著降低(P0.05)。结论:脂联素可抑制重症急性胰腺炎炎症发展,其可通过下调NF-κB通路及抑制促炎因子TNF-α发挥抗炎作用。     

脂联素在急性肺损伤中的研究进展

急性肺损伤(acute lung injury,ALI)是指在严重感染、休克、烧创伤等多种非心源性致病因素作用下导致的肺泡-毛细血管通透性增加,造成弥漫性肺间质与肺实质水肿,临床表现为进行性低氧血症,严重时表现为急性呼吸窘迫综合征(acute respiratory distress syndrome,ARDS),甚至可进展为致命性呼吸衰竭[1-3]。流行病学调查显示,目前ALI的发病率及病死率仍较高,在美国的发病率为86.2/10万,中国的住院患者发病率约为6.8%,病死率约为40%[4]。近些年来,ALI的基础研究和临床研究都取得了一些进展,但其病死率仍然居高不下[5-7]。如能进一步阐明其发病机制,在早期阶段对病情进行及时的评估和干预,有望进一步降低病死率和改善预后[2]。脂联素是脂肪组织分泌的一种特征性蛋白质,其血清水平在脂肪量增多时反而下降,在慢性炎症性疾病的发生发展过程中发挥重要作用[8]。ALI作为一种以炎症损伤为主要发病机制的疾病,近年来有大量文献报道了其与脂联素之间的关系,并提示脂联素在ALI的发生发展中发挥重要作用[9]。因此,本文就脂联素在ALI中的作用机制及应用作一简要综述。     

慢性肾脏病中脂联素及脂联素受体的变化及其意义

脂联素是脂肪细胞分泌的一种特异性蛋白质,具有改善胰岛素抵抗、抗炎、抗动脉粥样硬化等作用。研究发现脂联素与肾脏疾病关系密切,脂联素在肾脏中具有抗炎、抗纤维化、抗氧化及改善血管内皮细胞功能等作用。有研究显示尿脂联素可能具有一定的肾脏保护作用。脂联素是通过其受体发挥作用的,人脂联素受体AdipoR1/R2在组织中广泛表达,AdipoR1/R2在肾脏疾病的发生发展中具有重要作用。研究脂联素及脂联素受体在肾脏疾病病中的作用,有助于慢性肾脏疾病的防治。     

哮喘肥胖患儿血清脂联素水平变化及其临床意义研究

目的探讨哮喘肥胖患儿血清脂联素水平的变化及其临床意义。方法 2014年1月至2015年12月,以120例确诊的哮喘急性发作期肥胖患儿为研究对象(哮喘组),并根据病情将患儿分为轻度亚组、中度亚组和危重度亚组。于患儿入院当天和出院当天检测血清脂联素、总氧化态(TOS)、总抗氧化态(TAS)和氧化应激指数(OSI)水平。以非哮喘肥胖儿童为对照组。结果哮喘组患儿出院时TOS、OSI水平较入院时明显下降(P0.05)。哮喘组患儿入院时脂联素水平低于对照组(P0.05),出院时脂联素水平较入院时明显上升(P0.05)。危重度亚组患儿TOS水平明显高于轻度亚组患儿(P0.05),脂联素水平则明显低于轻度亚组患儿(P0.05)。以患儿入院时血清脂联素水平2.3mg/L作为cut-off值,则脂联素诊断肥胖患儿哮喘急性发作期的受试者工作特征曲线下面积为0.799(95%置信区间:0.699~0.878),灵敏度为85.6%,特异度为80.4%。脂联素与哮喘急性发作和严重程度分级呈负相关,与TOS、OSI亦呈负相关(P0.05)。OSI16.1U和脂联素水平2.3mg/L是哮喘急性发作的独立危险因素(P0.05)。结论脂联素通过调控氧化应激水平参与肥胖患儿哮喘急性发作的病理学发病机制。脂联素可作为肥胖患儿哮喘急性发作的潜在标记物。     

脂联素对小鼠主动脉平滑肌细胞体外钙化作用机制的研究

[目的]探讨脂联素对主动脉平滑肌细胞(ASMCs)体外钙化的作用机制.[方法]体外培养脂联素基因敲除小鼠ASMCs,以α-磷酸奈酚法检测钙化指标碱性磷酸酶(ALP),Western Blot检测脂联素受体(AdipoR)表达及丝裂原活化蛋白激酶(MAPK)激活.siRNA-AdipoR或加用MAPK信号转导阻断剂,观察脂联素对ASMCs钙化作用的变化.[结果]在小鼠ASMCs检测出AdipoR 1表达.脂联素干预后激活p38MAPK.若抑制AdipoR 1表达或使用p38 MAPK信号转导阻断剂SB203580,脂联素抑制ALP活性的作用消失.[结论]脂联素通过AdipoRl/p38信号转导途径抑制小鼠ASMCs体外钙化.     

内脏脂肪素与动脉粥样硬化

脂肪组织不仅是储存能量的器官,还是一个内分泌器官,通过其所分泌的一系列脂肪细胞因子,如脂联素、瘦素、抵抗素和肿瘤坏死因子等,与代谢综合征及心血管疾病建立了密切的关联。内脏脂肪素（visfatin）是脂肪组织分泌的重要产物,还可来源于中性粒细胞、巨噬细胞等免疫细胞,参与脓毒症中粒细胞凋亡的延迟、急性肺损伤、凝血酶诱导的肺气血屏障功能障碍等肺部炎症。此外,visfatin在动脉粥样硬化（atherosclerosis,AS）斑块中的发现,表明其可能作为一种炎症介质在AS形成机制中起重要作用。现就visfatin与AS的关系综述如下。     

脂联素在脂肪组织切口愈合中的作用及机制研究

目的 观察脂联素在脂肪组织切口愈合（ATWH）中的作用,探讨脂联素在ATWH中的作用机制.方法 制作猪ATWH模型;随机分为脂联素干预组和对照组（各组n=5）,观察ATWH等级,分析脂联素对ATWH的影响.应用免疫荧光标记技术和电镜观察脂肪细胞凋亡变化情况,分析脂联素水平对脂肪细胞凋亡的影响.结果 干预组切口愈合等级显著优于对照组（P〈0.05）;干预组脂肪细胞凋亡率明显少于对照组（P〈0.05）.结论 脂联素通过抑制脂肪细胞的凋亡促进ATWH.     

水飞蓟宾对非酒精性脂肪性肝病大鼠脂联素和抵抗素表达的影响

目的:研究水飞蓟宾对非酒精性脂肪性肝病(NAFLD)大鼠血清、肝脏、脂肪组织、骨骼肌中脂联素及抵抗素基因水平表达的影响,探讨水飞蓟宾防治NAFLD的可能作用机制.方法:通过6周高脂饮食建立NAFLD大鼠模型,采用水飞蓟宾进行干预,与已知有疗效的罗格列酮比较,用ELISA及Realtime-PCR等方法检测各组大鼠血清、肝脏、脂肪组织以及骨骼肌中脂联素和抵抗素的表达水平.结果:药物干预后大鼠血清、肝脏、脂肪组织中脂联素基因表达水平较模型组升高,抵抗素基因表达水平下降(P ＜ 0.05).水飞蓟宾对血清及脂肪组织脂联素的表达促进作用优于罗格列酮,对于肝脏脂联素表达的促进作用逊于罗格列酮(P ＜ 0.05).骨骼肌中脂联素及抵抗素表达水平极低,高脂饮食以及药物干预对其影响无统计学差异.结论:水飞蓟宾有效地促进脂联素表达,抑制抵抗素表达,这可能是其防治NAFLD的作用机制之一.     

脂联素与自身免疫性疾病

脂肪细胞分泌的各种脂肪因子如脂联素、瘦素、抵抗素等参与机体众多的生理过程,包括调节糖代谢、脂代谢、造血、炎症、补体激活、血栓形成等.脂联素是脂肪细胞专一分泌的多功能激素蛋白,在免疫病理和炎症过程中发挥重要作用.随着人们对自身免疫性疾病发病机制的不断深入研究,脂联素在自身免疫性疾病发生发展中的作用备受关注,本文就脂联素在自身免疫性疾病中的研究进展进行综述.     

急性脑梗死血清脂联素检测的临床价值

目的:研究急性脑梗死患者血清脂联素水平检测的临床价值.方法:用ELISA法测定344例急性脑梗死患者(初发组252例和复发组92例)及100例正常人血清脂联素水平,并进行统计学分析.结果:(1)各类型急性脑梗死患者血清脂联素均低于正常人(P<0.01);各类型脑梗死患者之间脂联素差异无显著性(P>0.05);(2)脑梗死复发患者血清脂联素低于初发患者(P<0.01);(3)1年内复发患者血清脂联素低于1年后复发者(P<0.05);(4)各类型脑梗死复发患者之间血清脂联素差异无显著性(P>0.05).结论:低脂联素水平与急性脑梗死的发生及复发均有密切关系,血清脂联素水平可以作为急性脑梗死风险因素和预后评估的临床指标.     

以TNF-α为靶点治疗急性肺损伤的研究进展

急性肺损伤（acute lung injury,ALI）是临床常见的呼吸系统急危重症,其发病机制复杂,病死率高。肿瘤坏死因子α（tumor necrosis factor—α,TNF—α）是ALI发生、发展过程中非常重要的细胞因子。本文就TNF—α在ALI中的作用和以抗TNF-α为靶点治疗ALI的相关研究进行综述。     

心搏骤停复苏后患者急性肝损伤发生的危险因素及对预后的影响

目的:探讨心搏骤停复苏后患者急性肝损伤发生的危险因素及对预后的影响。方法:回顾性分析2015年1月至2018年1月间本科心肺复苏术后患者的临床资料,按照是否发生急性肝损伤（acute liver injury,ALI）,将入选患者分为ALI组和非ALI组,比较两组患者入科时的基本情况及是否发生心搏骤停后休克及心功能不全。使用单因素生存曲线（Kaplan-Meier法）分析ALI对患者1年生存率的影响。观察ALI组患者的28 d病死率和神经功能恢复情况。使用多元逻辑回归分析ALI发生的危险因素。结果:入选ALI组54人,非ALI组158人,ALI组患者恢复自主循环的时间较长[19（10~27）min, P=0.015],ALI组患者总体病情（SOFA评分、酸中毒和乳酸）较重。ALI组和非ALI组心搏骤停后休克和心功能衰竭的发生率分别为74% vs. 55%和89% vs.70%。非ALI组患者的1年累计生存率明显高于ALI组,Log Rank (Mantel-Cox) χ2=4.102,差异有统计学意义（ P=0.043）。ALI持续时间越长,不良预后的发生率越高。心搏骤停后恢复自主循环的时间及心肺复苏后患者是否发生心力衰竭和ALI的发生相关, OR值分别为3.762（2.347~5.098）和4.272（2.943~5.932）, P<0.05。 结论:心搏骤停后恢复自主循环的时间及心肺复苏后的心力衰竭是ALI的危险因素,ALI的发生增加患者病死率。     

心搏骤停复苏后患者急性肝损伤发生的危险因素及对预后的影响

目的:探讨心搏骤停复苏后患者急性肝损伤发生的危险因素及对预后的影响。方法:回顾性分析2015年1月至2018年1月间本科心肺复苏术后患者的临床资料,按照是否发生急性肝损伤（acute liver injury,ALI）,将入选患者分为ALI组和非ALI组,比较两组患者入科时的基本情况及是否发生心搏骤停后休克及心功能不全。使用单因素生存曲线（Kaplan-Meier法）分析ALI对患者1年生存率的影响。观察ALI组患者的28 d病死率和神经功能恢复情况。使用多元逻辑回归分析ALI发生的危险因素。结果:入选ALI组54人,非ALI组158人,ALI组患者恢复自主循环的时间较长[19（10~27）min, P=0.015],ALI组患者总体病情（SOFA评分、酸中毒和乳酸）较重。ALI组和非ALI组心搏骤停后休克和心功能衰竭的发生率分别为74% vs. 55%和89% vs.70%。非ALI组患者的1年累计生存率明显高于ALI组,Log Rank (Mantel-Cox) χ2=4.102,差异有统计学意义（ P=0.043）。ALI持续时间越长,不良预后的发生率越高。心搏骤停后恢复自主循环的时间及心肺复苏后患者是否发生心力衰竭和ALI的发生相关, OR值分别为3.762（2.347~5.098）和4.272（2.943~5.932）, P<0.05。 结论:心搏骤停后恢复自主循环的时间及心肺复苏后的心力衰竭是ALI的危险因素,ALI的发生增加患者病死率。     

Experimental models and emerging hypotheses for acute lung injury

Acute lung injury (ALI) involves the activation of multiple pathways leading to lung injury, resolution, and repair. Exploration of the roles of individual pathways in humans and animal models has led to a greater understanding of the complexity of ALI and the links between ALI and systemic multiorgan failure. However, there is still no integrated understanding of the initiation, the progression, and the repair of ALI. A better understanding is needed of how pathways interact in the human ALI syndrome and how complementary treatments can be used to modify the onset, severity, and outcome of ALI in humans.     

急性肺损伤治疗措施的研究进展

急性肺损伤(acute lung injury,ALI)及其严重形式急性呼吸窘迫综合征(acute respiratory distress syndrome,ARDS)是临床常见的急危重症,此类患者住院时间长、病死率高,其标志性病理特征为肺部炎症和肺组织结构破坏,主要临床表现为低氧合和低肺顺应性。ALI的发病机制并不是很明确,目前已知氧化应激及炎症反应失控是其发生发展的重要机制。临床上ALI常用治疗手段包括药物和机械通气等综合疗法,但其病死率仍居高不下。新兴的治疗方式如干细胞、分子靶向疗法等已取得一定研究成果,有望成为ALI潜在的可靠治疗方法。     

Acute lung injury and acute respiratory distress syndrome at the intensive care unit of a general university hospital in Brazil. An epidemiological study using the American-European Consensus Criteria

OBJECTIVES: To determine: (1) the frequency of acute lung injury (ALI)/acute respiratory distress syndrome (ARDS); (2) the mortality associated with these syndromes and (3) the influence of risk factors, comorbidities and organ system dysfunction in the mortality of ALI patients. DESIGN: Prospective cohort study. SETTING: Intensive care unit (ICU) of a general university hospital in Brazil. PATIENTS AND PARTICIPANTS: All patients that remained in the ICU for more than 24 h were evaluated regarding the presence/development of ALI/ARDS according to the 1994 American-European Consensus Conference. INTERVENTIONS: None. MEASUREMENTS AND RESULTS: One thousand three hundred and one patients were studied and analyzed regarding mortality, risk factors, comorbidities and organ system dysfunction(s). The frequency of ALI was 3.8% (50), of which ARDS was 2.3% (30) and ALI/non-ARDS 1.5% (20) (p=0.15). The ICU mortality of patients with ALI was 44.0%; in ALI/non-ARDS and ARDS patients it was 40.0% and 46.7%, respectively (p=0.43). The hospital mortality of ALI patients was 48.0%; in ALI/non-ARDS and ARDS patients it was 50.0% and 46.7%, respectively (p=0.21). A multivariate analysis demonstrated that renal (ICU and hospital: p=0.002) and hematological dysfunction (ICU: p=0.008; hospital: p=0.02) were independently associated with ICU and hospital mortality in ALI patients. CONCLUSIONS: (1) The frequency of ALI was 3.8%, of which the frequency of ARDS was 2.3% and of ALI/non-ARDS 1.5%; (2) The ICU and hospital mortality of ALI patients was 44.0% and 48.0%, respectively; mortality rates of ARDS and ALI/non-ARDS did not differ significantly; (3) Renal and hematological dysfunction were associated with mortality in ALI patients.     

Towards prevention of acute lung injury: frequency and outcomes of emergency department patients at-risk - a multicenter cohort study

ABSTRACT: BACKGROUND: Few emergency department (ED) evaluations on acute lung injury (ALI) have been carried out; hence, we sought to describe a cohort of hospitalized ED patients at risk for ALI development. METHODS: Patients presenting to the ED with at least one predisposing condition to ALI were included in this study, a subgroup analysis of a multicenter observational cohort study (USCIITGLIPS 1). Patients who met ALI criteria within 6 h of initial ED assessment, received end-oflife care, or were readmitted during the study period were excluded. Primary outcome was frequency of ALI development; secondary outcomes were ICU and hospital mortality. RESULTS: Twenty-two hospitals enrolled 4,361 patients who were followed from the ED to hospital discharge. ALI developed in 303 (7.0%) patients at a median onset of 2 days (IQR 2-5). Of the predisposing conditions, frequency of ALI development was highest in patients who had aortic surgery (43%) and lowest in patients with pancreatitis (2.8%). Compared to patients who did not develop ALI, those who did had higher ICU (24% vs. 3.0%, p < 0.001) and hospital (28% vs. 4.6%, p < 0.001) mortality, and longer hospital length of stay (16 vs. 5 days, p < 0.001). Among the 22 study sites, frequency of ALI development varied from less than 1% to more than 12% after adjustment for APACHE II. CONCLUSIONS: Seven percent of hospitalized ED patients with at least one predisposing condition developed ALI. The frequency of ALI development varied significantly according to predisposing conditions and across institutions. Further research is warranted to determine the factors contributing to ALI development.     

留置胃管导致医院获得性肺部感染的预防现状

综述留置胃管导致医院获得性肺部感染(ALI)的预防现状,包括ALI的发生率及其诊断、ALI的危害、引发ALI的相关因素及预防,指出ALI的发生与留置胃管相关,缩短留置时间可减少ALI的危险因素。     

Clinical review: Early treatment of acute lung injury - paradigm shift toward prevention and treatment prior to respiratory failure

ABSTRACT: Acute lung injury (ALI) remains a major cause of morbidity and mortality in critically ill patients. Despite improved understanding of the pathogenesis of ALI, supportive care with a lung protective strategy of mechanical ventilation remains the only treatment with a proven survival advantage. Most clinical trials in ALI have targeted mechanically ventilated patients. Past trials of pharmacologic agents may have failed to demonstrate efficacy in part due to the resultant delay in initiation of therapy until several days after the onset of lung injury. Improved early identification of at-risk patients provides new opportunities for risk factor modification to prevent the development of ALI and novel patient groups to target for early treatment of ALI before progression to the need for mechanical ventilation. This review will discuss current strategies that target prevention of ALI and some of the most promising pharmacologic agents for early treatment of ALI prior to the onset of respiratory failure that requires mechanical ventilation.     

不同病因致急性肺损伤患儿可溶性细胞间黏附分子-1的变化和临床意义

目的探讨肺内外原因引起的急性肺损伤(ALI)患儿可溶性细胞间黏附分子-1(sICAM-1)的变化及临床意义。方法肺内源性ALI患儿32例,肺外源性ALI患儿35例,使用ELISA双抗体夹心法动态检测ALI诊断成立后1、24、48、72h血清sICAM-1的表达。结果两组患儿在确诊ALI后sICAM-1均较正常值明显升高(P<0.01),肺外源性ALI患儿在确诊ALI1h时sICAM-1即开始明显升高,24h达高峰,至48h开始逐渐下降,1h和24h的sICAM-1较肺内源性ALI患儿明显升高(P<0.01),而sICAM-1在肺内源性ALI患儿的整个疾病过程中变化不明显(F=1.88,P>0.05)。结论肺内、外源性ALI患儿外周血中sICAM-1浓度的变化有明显差异。