A new approach to HLA typing designed for solid organ transplantation: epityping and its application to the HLA‐A locus

HLA‐specific antibodies bind discrete clusters of amino acids called epitopes, but serological assignment of antibody specificities makes no reference to this. As HLA typing for solid organ transplantation is provided at only medium (serologically equivalent) resolution, this means that recipient HLA antibodies to donor HLA epitopes may not be identified. We have designed a novel and rapid HLA‐A epitope typing method (epityping) using a two‐stage PCR‐SSP‐based method to detect the HLA‐A locus epitopes described by El Awar et al. 2007, Transplantation, 84 , 532. The initial PCR step utilizes HLA‐A locus‐specific primers; the product is cleaned using the QIAquick Spin Purification procedure. The purified product is tested using our in‐house epitope‐specific primer panel, the results being visualized using gel electrophoresis. Twenty two UCLA DNA Exchange samples were epityped, blinded to the HLA type. Of the 75 primer pairs, the mean correlation coefficient was 0.95 with each sample giving 67 or more correct primer results. In all cases, it was possible to derive the first field classic HLA type from the epityping results. These results indicate that a method for identification of HLA epitopes which is comparable in time, cost and technical expertise to current HLA typing methods is achievable. Redesigning HLA typing to correlate with what the antibody binds should minimize inappropriate organ allocation. We suggest that epityping provides a more effective method than standard HLA typing for solid organ transplantation.     

Heart transplantation with donor-specific antibodies directed toward denatured HLA-A*02:01: a case report

The development of solid-phase assays for antibody detection has aided in the frequent detection of human leukocyte antigen (HLA) antibodies in nonalloimmunized males. Some scientists have reported that these HLA antibodies are produced to pathogens or allergens and the reactivity with HLA coated beads is the result of cross-reactive epitopes. These antibodies may also be directed toward cryptic epitopes exposed on the denatured beads. In this report, we describe the case of a heart transplanted patient who exhibited anti-HLA-A*02:01 donor-specific antibodies detected with a bead-based assay (Luminex) and undetected with the complement-dependent cytotoxicity (CDC) test. Posttransplant monitoring, carried out with CDC and with Luminex on sera from this patient collected at the 2nd, 4th, 8th, and 12th posttransplant weeks and at 1 year confirmed the presence of anti-HLA-A*02:01 in all serum samples. Additional tests carried out with denatured and intact HLA molecules using single antigen beads demonstrated that the antibody was directed toward a cryptic epitope. One year after transplantation the patient is doing well. No sign of antibody-mediated rejection was observed throughout the follow-up. A comprehensive evaluation of the anamnesis and of antibodies is critical to avoid needless exclusion of organ donors.     

A shift in the collagen V antigenic epitope leads to T helper phenotype switch and immune response to self-antigen leading to chronic lung allograft rejection

Immune responses to human leucocyte antigen (HLA) and self-antigen collagen V (Col-V) have been proposed in the pathogenesis of chronic rejection (bronchiolitis obliterans syndrome, BOS) following human lung transplantation (LTx). In this study, we defined the role for the shift in immunodominant epitopes of Col-V in inducing T helper phenotype switch leading to immunity to Col-V and BOS. Sera and lavage from BOS(+) LTx recipients with antibodies to Col-V were analysed. Two years prior to BOS, patients developed antibodies to both Col-V,α1(V) and α2(V) chains. However, at clinical diagnosis of BOS, antibodies became restricted to α1(V). Further, lung biopsy from BOS(+) patients bound to antibodies to α1(V), indicating that these epitopes are exposed. Fourteen Col-V peptides [pep1-14, pep1-4 specific to α1(V), pep5-8 to α1,2(V) and pep9-14 to α2(V)] which bind to HLA-DR4 and -DR7, demonstrated that prior to BOS, pep 6, 7, 9, 11 and 14 were immunodominant and induced interleukin (IL)-10. However, at BOS, the response switched to pep1, 4 and 5 and induced interferon (IFN)-γ and IL-17 responses, but not IL-10. The T helper (Th) phenotype switch is accompanied by decreased frequency of regulatory T cells (T(regs) ) in the lavage. LTx recipients with antibodies to α1(V) also demonstrated increased matrix metalloproteinase (MMP) activation with decreased MMP inhibitor, tissue inhibitor of metalloproteinase (TIMP), suggesting that MMP activation may play a role in the exposure of new Col-V antigenic epitopes. We conclude that a shift in immunodominance of self-antigenic determinants of Col-V results in induction of IFN-γ and IL-17 with loss of tolerance leading to autoimmunity to Col-V, which leads to chronic lung allograft rejection.     

Soluble donor HLA class I and β2m-free heavy chain in serum of lung transplant recipients: steady-state levels and increases in patients with recurrent CMV infection, acute rejection episodes, and poor outcome

We determined the concentration of donor sHLA/β₂m and total β₂m-free heavy chain (HC) in the serum of lung transplant recipients with ELISA assays. While we were unable to detect specific donor β₂m-free HCs due to a lack of available antibodies, we could determine if events that led to an increase in the release of β₂m-free HC also led to an increase in the release of donor sHLA/β₂m, particularly the 36 kDa, proteolytically cleaved form. We found that lung transplants constituitively release donor sHLA/β₂m at ng/ml levels. The levels (both of donor sHLA/β₂m and total β₂m-free HC) were significantly increased in CMV-sero-negative recipients (but not in CMV-sero-positive recipients) at the onset of post-transplant CMV disease. Acute rejection episodes were also associated with an increased release of donor sHLA/β₂m, but not of β₂m-free HC. However, in patients with particularly poor outcome (i.e., graft loss within 1 year) there was a significant release of β₂m-free HC. Analysis of one such patient showed a predominance of 36 kDa forms of donor-sHLA/β₂m. Our data are consistent with the hypothesis that the metalloproteinase that cleaves β₂m-free HC is active during uncontrolled CMV infection and acute rejection. However, recall responses to CMV and controlled immune responses to donor may result in little or no activation of sHLA class I release.     

miR-133b has protective effect on rats with acute lung injury caused by severe acute pancreatitis through targeting sp1 gene

Objective: We aimed to investigate the regulatory mechanism of miR-133b and Sp1 in rats with severe acute pancreatitis complicated by acute lung injury. Methods: The rats were divided into normal, NC, model, si-Sp1, miR-133b mimic, miR-133b inhibitor, and miR-133b inhibitor + si-Sp1 group and received different treatments. Results: Compared with normal mice, model mice had a lower miR-133b expression, but higher levels of Sp1 expression, W/D of lung tissue, myeloperoxidase activities, and higher levels of interleukin(IL)-6, tumor necrosis factor (TNF)-α and IL-1β, cell apoptosis rate and Notch-1, and Hes-1, nuclear factor (NF)-κB P65 expressions in lung tissue. Compared with model mice, mice in the si-Sp1 group and the miR-133b mimic group had significantly lower W/D of lung tissue, myeloperoxidase activities, lower levels of IL-6, TNF-α and IL-1β, cell apoptosis rate and Notch-1, Hes-1, and NF-κB P65 expressions in lung tissue. Mice treated by miR-133b inhibitor showed opposite results in all above parameters, which were similar with those in the model group. The negative effects of miR-133b inhibitor could be reversed by the combination use of si-Sp1. Conclusion: Overexpression of miR-133b could inhibit Sp1 expression, thereby improving severe acute pancreatitis in rats and playing a protective role in acute lung injury.     

急诊肺炎患者发生急性肺损伤/急性呼吸窘迫综合征危险因素分析

目的探讨急诊肺炎患者发生急性肺损伤(ALI)/急性呼吸窘迫综合征(ARDS)的早期危险因素。方法回顾性分析中国医科大学附属第一医院急诊科收治的100例肺炎患者,其中男性62例,女性38例;年龄49~79岁,平均年龄62岁。观察72h,发展至ALI/ARDS为ALI/ARDS组,未发展至ALI/ARDS的分为单纯肺炎组。收集两组患者的年龄、性别、生命体征、初始所需吸氧浓度及初诊的实验室检查(白细胞、血小板计数、血清白蛋白、尿素氮、丙氨酸氨基转移酶)指标,对各项因素进行单因素分析,单因素分析有显著意义的变量行二项分类的Logistic回归分析。结果 100例患者35例发展为ALI/ARDS,65例未发展为ALI/ARDS。单因素分析结果显示,患者是否发展为ALI/ARDS与年龄、性别、体温、呼吸频率、休克、白细胞计数、尿素氮等比较,差异无统计学意义(P0.05);初始所需吸氧浓度(维持血氧饱和度≥90%)、改良后的快速急诊内科评分(REMS)、低蛋白血症与发展为ALI/ARDS差异有统计学意义(P0.05)。二项分类的Logistic回归分析显示,仅吸氧浓度、改良后的REMS评分是发展为ALI/ARDS的独立危险因素。其中吸氧浓度2 L/min的灵敏度为77.1%,特异度为86.2%;改良后的REMS≥7发生ALI/ARDS灵敏度为74.3%,特异度为72.3%。结论初始吸氧浓度及改良后的REMS评分与ALI/ARDS的发生存在正相关,初始吸氧浓度2 L/min和/或改良后的REMS≥7的肺炎患者应予以重视,是ALI/ARDS的高危患者,争取做到早期诊治。     

Hypoxia aggravates lipopolysaccharide-induced lung injury

The animal model of inflammatory response induced by intratracheal application of lipopolysaccharide includes many typical features of acute lung injury or the acute respiratory distress syndrome. A number of experimental investigations have been performed to characterize the nature of this injury more effectively. In inflammatory conditions, hypoxia occurs frequently before and in parallel with pulmonary and non-pulmonary pathological events. This current study was designed to examine the in vivo effect of hypoxia as a potentially aggravating condition in endotoxin-induced lung injury. Lipopolysaccharide, 150 microg, was instilled intratracheally into rat lungs, and thereafter animals were exposed to either normoxia or hypoxia (10% oxygen). Lungs were collected 2, 4, 6 and 8 h later. Inflammatory response and tissue damage were evaluated by quantitative analysis of inflammatory cells and mediators, surfactant protein and vascular permeability. A significantly enhanced neutrophil recruitment was seen in lipopolysaccharide-animals exposed to hypoxia compared to lipopolysaccharide-animals under normoxia. This increased neutrophil accumulation was triggered by inflammatory mediators such as tumour necrosis factor-alpha and macrophage inflammatory protein-1beta, secreted by alveolar macrophages. Determination of vascular permeability and surfactant protein-B showed enhanced concentrations in lipopolysaccharide-lungs exposed to hypoxia, which was absent in animals previously alveolar macrophage-depleted. This study demonstrates that hypoxia aggravates lipopolysaccharide injury and therefore represents a second hit injury. The additional hypoxia-induced inflammatory reaction seems to be predominantly localized in the respiratory compartment, underlining the compartmentalized nature of the inflammatory response.     

急性肺损伤大鼠肺组织CC16的表达及其对肺局部炎症反应的调控

研究CC16在内毒素急性肺损伤(ALI)发病中的作用。取56只雄性SD大鼠随机分为对照组、内毒素致伤后0.5、1、2、4、6、24h组。用体视学方法测定大鼠肺泡隔面积密度(PASAD)和肺泡隔中性粒细胞(PMN)数。大鼠肺组织匀浆液中CC16蛋白含量测定用Westernblot法,促炎因子TNF和IL-6含量测定用放免分析法。肺组织CC16mRNA表达水平测定用半定量RT-PCR法。大鼠肺组织中核因子NF-κB的表达与活化用免疫荧光和Westernblot法。结果显示静脉注射内毒素后6h内,大鼠PASAD逐渐增大,于6h达最大,24h基本恢复至正常,肺泡隔PMN数进行性增多,于6h达峰值,24h恢复。伤后各时相点CC16蛋白水平分别为(0.740±0.212)、(0.630±0.148)、(0.603±0.111)、(0.570±0.125)、(0.529±0.124)、(0.614±0.185),均明显低于对照组(1.000),差异有高度统计学意义(P<0.01)。致伤后各时相点大鼠CC16mRNA表达水平均明显低于对照组水平,差异有统计学意义。致伤后各时相点肺组织中NF-κB阳性细胞数均明显多于对照组。致伤后各时相点大鼠肺匀浆液中IκB-α含量明显低于对照组。肺匀浆液中促炎因子TNF水平于致伤后0.5h开始迅速升高,于伤后1h达峰值,其后维持在一种高水平状态,于6h后开始恢复。肺匀浆液中IL-6水平于伤后1h开始明显升高,于伤后4h达峰值,6h后开始恢复。CC16与上述多种指标显著相关,提示CC16对肺局部炎症反应有调控作用。CC16表达变化在内毒素致急性肺损伤的发病中有重要作用。     

Ang-2在大鼠内毒素性急性肺损伤中的作用

目的:探讨促血管生成素2 (Ang-2 )在不同程度急性肺损伤(ALI)中的作用.方法:清洁级SD大鼠共40只, 随机分为4组: 正常对照组, 不同剂量大肠杆菌脂多糖(LPS)组(3个剂量组: 2 mg/kg、 4 mg/kg及8 mg/kg), 每组平均10只.HE染色光镜观察肺组织标本病理改变并进行肺损伤评分, Western blot检测各组大鼠血浆中Ang-2的表达情况.结果:LPS可致肺泡间隔增宽、出血及大量炎性细胞浸润等急性肺损伤病理改变, LPS各组的肺损伤评分明显高于正常对照组(P<0.01);LPS不同剂量与肺损伤评分呈量效依赖关系(P<0.05).LPS不同剂量组的血浆中Ang-2蛋白表达较空白对照组增高(P<0.01), LPS不同剂量与Ang-2蛋白表达水平呈量效依赖关系(P<0.05).血浆中Ang-2的蛋白表达与肺组织炎症程度积分呈正相关(r=0.862, P<0.05).结论:Ang-2参与大鼠内毒素性急性肺损伤的病理过程, 且血浆Ang-2水平与急性肺损伤程度呈正相关.     

Acute respiratory distress syndrome: Pulmonary and extrapulmonary not so similar

Acute respiratory distress syndrome (ARDS) is characterized by acute onset respiratory failure with bilateral pulmonary infiltrates and hypoxemia. Current evidence suggests different respiratory mechanics in pulmonary ARDS (ARDSp) and extrapulmonary ARDS (ARDSexp) with disproportionate decrease in lung compliance in the former and chest wall compliance in the latter. Herein, we report two patients of ARDS, one each with ARDSp and ARDSexp that were managed using real-time esophageal pressure monitoring using the AVEA ventilator to tailor the ventilatory strategy.     

Antiinflammatory effects of adalimumab,tocilizumab, and steroid on lipopolysaccharide-induced lung injury

Background/aimAcute lung injury (ALI) is a major cause of death in the intensive care unit. Lipopolysaccharide (LPS) induced lung injury is the most widely used experimental ALI model and provides opportunities for new targeting therapy. In this study, we investigated the effects of tocilizumab, adalimumab, and methylprednisolone in LPS-induced acute lung injury.Materials and methodsLung injury was established by intratracheal instillation of LPS. The rats were randomly divided into six groups: LPS, control, and treatment groups (adalimumab, tocilizumab, methylprednisolone, adalimumab + tocilizumab). Bronchoalveolar lavage (BAL) and lung tissues were collected at 48 h and 96 h following LPS administration from each group. For histological analysis, hematoxylin–eosin (H&E) staining was performed. The sections were obtained for immunohistochemical analysis. IL-6 and TNF-alpha immunoreactivity were measured. ResultsIntratracheal LPS application resulted in inflammatory cell infiltration of interstitial and alveolar spaces and thickening of the alveolar wall. All treatment groups showed significantly amelioration compared to LPS at 48 h. Interestingly, adalimumab and adalimumab + tocilizumab groups showed a significant amelioration of the lung histoarchitecture, compared to the prednisolone group at 96 h (p = 0.028, p = 0.025, respectively). Compared to the control group, LPS stimulation resulted in a significant increase in IL-6 and TNF-alpha immunoreactivity (p < 0.001). IL-6 and TNF-alpha expression were markedly reduced in all treatment groups at 48 h but the reduction was greater in the adalimumab and tocilizumab group than in the steroid. Administration with adalimumab and/or tocilizumab effectively decreased expression of TNF-alpha (p = 0.001) and IL-6 (p < 0.001) at 96 h, but prednisolone did not exert an effective decrease (p > 0.05). ConclusionAdalimumab and/or tocilizumab significantly reduce the release of proinflammatory cytokines and improve the tissue inflammation in the experimental model of ALI. Our results suggest that adalimumab and/or tocilizumab have a more potent antiinflammatory effect on lung injury than the steroid.     

Soluble endothelial selectin in acute lung injury complicated by severe pneumonia

Background: Pneumonia is still one of the most frequent causes of death in the elderly. Complication of acute lung injury (ALI)/acute respiratory distress syndrome (ARDS) by pneumonia makes patients very ill due to severe respiratory failure. Biomarkers that can discriminate the presence of complicating ALI/ARDS are required for early detection. The aim of this research was to investigate whether soluble endothelial selectin (sES) could be a biomarker for ALI.Methods: Serum sES levels were measured in 27 pneumonia patients, who were enrolled between April 2006 and September 2007. Among these patients, six had ALI or a condition that was clinically comparable to ALI (cALI). All patients who were enrolled were successfully treated and survived.Results: Circulating sES levels were elevated in pneumonia patients with ALI/cALI, and sES levels decreased following treatment of their pneumonia. Univariate and multivariate logistic regression analyses showed that sES was the only significant factor for identifying complicating ALI/cALI, independently of C-reactive protein (CRP) and lactate dehydrogenase (LDH). By receiver operating characteristic (ROC) curve analysis, the cut-off value for sES was 40.1 ng/mL, with a sensitivity of 0.8 and a specificity of 0.8.Conclusion: sES may be a useful biomarker for discriminating complicating ALI/cALI in patients with severe pneumonia.     

延胡索乙素对大鼠急性放射性肺损伤的保护作用

目的:探讨延胡索乙素(dl-tetrahydropalmatine,THP)对大鼠急性放射性肺损伤(irradiation induced lung injury,RILI)的保护作用.方法:成年雌性SD大鼠随机分为4组,对照组、单纯照射组(R组)、R+THP组、THP组.R组采用x射线右侧胸部单次照射15 Gy,于照射后1,4,8,12,16周分别处死大鼠,取肺组织行TUNEL及电镜检测凋亡,HE染色观察病理变化,部分肺组织行超氧化物歧化酶(superoxide dismutase,SOD)及丙二醛(malondialdehyde,MDA)检测,ELISA法测定大鼠血清TGF-p1.结果:对照组及THP组大鼠肺组织均无炎症反应.受照射组(R组、R+THP组)在照射后4～16周均表现出不同程度的肺组织细胞凋亡及RILI病理变化;但R+THP组较R组炎症反应明显减轻,R+ THP组与同时段的R组比较:肺组织中MDA水平明显降低、SOD水平明显升高,血清中TGF-p1明显降低,炎性细胞募集较少.两组间不同时段血清中TGF-p1水平、肺组织中MDA,SOD水平以及肺组织细胞的凋亡指数均有显著性差异(P＜0.05或P＜0.01).结论:THP能通过抑制凋亡、减轻氧化损伤、抑制TGF-p1等作用减轻大鼠急性RILI.     

黄连素对金黄色葡萄球菌急性肺损伤的保护作用及相关机制研究

目的 探讨黄连素(berberine,BBR)对金黄色葡萄球菌(Staphylococcus aureus,SA)诱导小鼠急性肺损伤的保护作用及相关机制.方法 对小鼠行气道滴注SA构建急性肺损伤模型和体外刺激巨噬细胞RAW264.7感染模型.通过苏木精伊红染色方法(hematoxylin-eosin staining,HE)检测各组小鼠肺组织病理变化,Western印迹检测细胞中核转录因子P65蛋白和磷酸化分子p-P65蛋白,以及各样本中肿瘤坏死因子-α(tumor necrosis factor-α,TNF-α)和白介素-6(interleukin-6,IL-6)的表达以评估黄连素对SA诱导的急性肺损伤的作用.结果 黄连素预处理可减轻SA诱导的急性肺损伤,减缓肺组织病理改变以及降低肺组织和细胞中炎性因子IL-6和TNF-α的表达并抑制p-P65蛋白的活化,但对P65的表达无影响.结论 黄连素可通过抑制P65炎症信号通路的发生进一步抑制炎性因子的释放从而对SA诱导的急性肺损伤起到保护作用.     

高容量血液滤过减轻脂多糖诱导犬急性肺损伤

目的 研究高容量血液滤过(HVHF)对脂多糖(LPS)诱导犬急性肺损伤(ALI)的治疗作用,并探讨其机制.方法 健康犬16条,静脉注入LPS(650 μg/kg) ,随机分为对照组(C组)和HVHF治疗组(T组).监测动脉血气.放免法测定血TNF-a、IL-6和IL一10含量,流式细胞仪测定肺组织NF-κB活性,免疫印迹法测定肺表面活性蛋白(SP-B)含量,电镜下观察肺组织病理改变.结果 动物注入LPS后Pa和PaO/FiO2下降,HVHF治疗后上述指标明显高于C组(P<0.01).治疗1 h血中TNF-α、IL-6和IL-IO的浓度即有明显下降,低于同时点C组(P<0.01).治疗4 h后,NF-κB活性度下降(P相似文献   

罗格列酮通过减少Th17细胞极化减轻LPS诱导的小鼠急性肺损伤

目的探讨罗格列酮(RSG)对急性肺损伤(ALI)小鼠的作用及可能的机制。方法 24只BALB/c小鼠,随机分为对照组(control)、模型组(LPS)、罗格列酮干预组(RSG)和GW9662拮抗组(GW9662),每组6只。分别检测支气管肺泡灌洗液(BALF)中炎性细胞分类计数和炎性因子水平、HE染色观察肺组织病理改变,Q-PCR和Western blot分别检测Th17细胞核转录因子RORγt及PPARγ的mRNA和蛋白表达。结果与对照组比较,模型组BALF中性粒细胞比例和炎性因子水平均显著增高(P0.05);肺组织RORγt高表达(P0.05)。接受罗格列酮干预小鼠PPARγ明显增高,炎性反应指标均较模型组减轻(P0.05),同时伴有RORγt表达降低。GW9662显著拮抗罗格列酮的保护作用,小鼠肺组织炎性反应显著,RORγt基因的mRNA和蛋白水平均较罗格列酮组回升(P0.05)。结论罗格列酮可通过活化PPARγ,进而抑制Th17细胞的分化,减轻由LPS诱导的小鼠急性肺损伤。     

Priming With Endotoxin Increases Acute Lung Injury in Mice by Enhancing the Severity of Lung Endothelial Injury

Endotoxin‐induced acute lung injury (ALI) is a commonly used model. However, the effect of a priming dose of endotoxin on lung fluid balance has not been well studied. We hypothesized that endotoxin‐induced ALI in mice would be enhanced under a priming condition. Mice were intratracheally (IT) instilled with either a priming dose of endotoxin from E. coli (0.5 mg/kg) or equal volume of PBS. Eighteen hours later, a larger challenge dose of endotoxin (5 mg/kg) was given IT. Control mice received PBS only. After 24 hr, the mice were sacrificed and the degree of lung injury and inflammation were measured. Endotoxin priming increased body weight loss and worsened hypothermia. Extravascular lung water and lung endothelial permeability were higher in the primed group. Priming with endotoxin reduced alveolar fluid clearance; however, there was no effect on bronchoalveolar lavage (BAL) levels of receptor for advanced glycation end products (RAGE). The primed group had increased alveolar inflammation as demonstrated by increased numbers of neutrophils in the BAL. There was no significant difference in NF‐κB p65 in the lung nuclear extract among the experimental groups. Taken together, priming with a small dose of endotoxin followed by a larger challenge dose of endotoxin induces more systemic illness and increased pulmonary edema in mice, largely due to increased lung endothelial permeability and lung inflammation. This model should be useful to investigators studying ALI who want to simulate the clinical setting in which more than one insult often leads to greater clinical lung injury. Anat Rec, 2010. © 2010 Wiley‐Liss, Inc.     

大黄对内毒素诱导急性肺损伤大鼠的保护作用

探讨脂多糖（LPS）致急性肺损伤（ALI）的作用机制及大黄的保护作用。用Wistar大鼠复制LL的的动物模型,观察组织病理学变化,测定ALI生物学指标及NO和iNOs。结果显示：LPS组肺间质水肿,肺泡腔内可见大量细胞润滑和血浆蛋白渗出;肺管内皮细胞损伤。肺湿干重比,肺泡灌洗液中中性粒细胞比例,蛋白含量及肺泡通透指数,肺毛细管通透性均显著升高,NO和iNOs也显著升高。地塞米松和大黄组,上述指标均较LPS组显著。LPS致LI的机制主要是直接损伤肺泡上和血管内皮细胞,大黄及地塞米松对血管内皮和肺泡上皮具有保护作用,其机制可能是通过抑制NO和iNOs活性实现。