内皮素受体拮抗剂BQ123对大鼠急性坏死性胰腺炎E-、P-选择素表达的影响

目的 观察急性坏死性胰腺炎（ANP）动物模型血管内皮细胞E-选择素和P-选择素（selectin）的变化特点以及用内皮素受体拮抗剂（ET-RA）BQ123治疗后的改变。方法 54只SD大鼠随机分为3组：正常组（n=6），ANP组（n=24），BQ123治疗组（ANP＋BQ123，n=24）。采用胰腺实质注射牛磺胆酸钠的方法制作ANP模型，制模后6h用BQ123进行治疗，监测制模后24h、48h、72h和7d血清淀粉酶活性；光镜下观察肺及胰腺组织白细胞浸润情况；免疫组化观察胰腺组织E-选择素、P-选择素表达；RT—PCR检测胰腺组织E-选择素、P-选择素mRNA变化。结果 ANP组肺及胰腺内大量白细胞浸润，而BQ123治疗组白细胞明显减少。ANP组胰腺选择素表达水平显著高于正常组水平，而BQ123治疗组较ANP组显著降低。结论 内皮素受体拮抗剂可通过调控ANP时选择素的表达水平，达到减少白细胞在局部器官浸润，保护器官功能的效果。     

内皮素受体拮抗剂 BQ123 对大鼠急性坏死性胰腺炎 E-、P- 选择素表达的影响

目的 观察急性坏死性胰腺炎(ANP)动物模型血管内皮细胞E-选择素和P-选择素(selectin)的变化特点以及用内皮素受体拮抗剂(ET-RA)BQ123治疗后的改变.方法 54只SD大鼠随机分为3组:正常组(n = 6),ANP组(n = 24),BQ123治疗组(ANP + BQ123,n = 24).采用胰腺实质注射牛磺胆酸钠的方法 制作ANP模型,制模后6 h用BQ123进行治疗,监测制模后24 h、48 h、72 h 和7 d血清淀粉酶活性;光镜下观察肺及胰腺组织白细胞浸润情况;免疫组化观察胰腺组织E-选择素、P-选择素表达;RT-PCR检测胰腺组织E-选择素、P-选择素mRNA变化.结果 ANP组肺及胰腺内大量白细胞浸润,而BQ123治疗组白细胞明显减少.ANP组胰腺选择素表达水平显著高于正常组水平,而BQ123治疗组较ANP组显著降低.结论 内皮素受体拮抗剂可通过调控ANP时选择素的表达水平,达到减少白细胞在局部器官浸润,保护器官功能的效果.     

低分子肝素对急性坏死性胰腺炎并肝损伤P-选择素和E-选择素表达的影响

目的研究低分子肝素(LWMH)对大鼠急性坏死性胰腺炎(ANP)并肝损伤中P-选择素和E-选择素表达的影响及其对急性坏死性胰腺炎的保护作用。方法将96只雄性SD大鼠随机分为三个组:对照组(C组,n=32)、急性坏死性胰腺炎组(A组,n=32)、低分子肝素干预组(G组,n=32)。A组以1.5%脱氧胆酸钠溶液逆行注入胰胆管建立急性坏死性胰腺炎模型(1 ml/kg),G组于造模后给予皮下注射低分子肝素(10 U/100 g),C组仅翻动胰腺后关腹。各组分别于造模后6、12、24、48 h四个时点分批处死大鼠,测定血清淀粉酶水平;E LISA检测血清TNF-α、IL-6水平,取胰腺及肝脏组织光镜下进行病理学评分;RT-PCR检测肝脏P-选择素和E-选择素mRNA表达。结果三组间和不同时点之间各项观察指标比较均有统计学意义(P0.01),A组6、12、24、48 h各时点胰腺及肝脏病理评分、血清淀粉酶及TNF-oα、IL-6水平,P-选择素和E-选择素mRNA表达均较C组相应时点显著升高(P0.05);G组各时点胰腺及肝脏病理评分、血清淀粉酶及TNF-oα、IL-6水平,P-选择素和E-选择素mRNA表达均较A组对应时点显著降低(P0.05)。结论 P-选择素和E-选择素在急性坏死性胰腺炎并肝损伤时的表达可能与病变严重程度有关;LWMH可能是通过下调P-选择素和E-选择素表达减轻急性坏死性胰腺炎的胰腺和肝脏病变。     

可溶性E-选择素在慢性阻塞性肺疾病、肺炎、支气管哮喘疾病中的表达及意义

E-选择素（E-selection）是细胞粘附分子中选择素家族中的一员，E-选择素介导白细胞在炎症和组织损伤区域的滚动，参与炎症过程起重要作用。本研究探讨可溶性E-选择素（sE-选择素）在呼吸系几种常见疾病中的表达和变化及其临床意义。     

急性冠脉综合征患者血清sCD40L与sP-选择素相关性研究

采用酶联免疫吸附法测定急性冠脉综合征（ACS）、不稳定型心绞痛（UAP）及健康对照者的血清可溶性CD40配体（sCD40L）、可溶性P-选择素（sP-选择素）水平。分析sCD40L和sP-选择素与ACS发生的关系。结果ACS组血清sCD40L、sP-选择素均显著高于SAP组和对照组（P〈0.01），ACS患者血清sCD40L与sP-选择素呈显著正相关（r=0．516，P〈0．01）。提示ACS患者血清sCD40L和sP-选择素明显升高可促进ACS的发生和发展。     

大鼠急性坏死性胰腺炎脂质代谢的研究

目的 察大鼠急性坏死性胰腺炎时血脂的代谢及其对炎症的影响。方法 36只SD大鼠（250g左右），随机分为对照组和急性坏死性胰腺炎（ANP）3h、6h、12h、24h、48h组，每组6只。除对照组外予胰管内逆行注射5％牛磺胆酸钠复制ANP大鼠模型，观察胰腺组织病理学和透射电镜的改变。检测各组血清淀粉酶、胆固醇、三酰甘油（TG）、游离脂肪酸（FFA）和脂蛋白脂酶（LPL）含量。Rq、-PCR检测硬脂酰基辅酶A脱氢酶（SCD）和脂肪酸转移酶（CD36）mRNA的表达。结果 清淀粉酶和胰腺病理学改变符合大鼠ANP改变特征，在12h组淀粉酶和胰腺病理学改变达峰值。电镜下ANP各组腺泡细胞粗面内质网扩张、酶原颗粒增多。ANP各组血清TG和FFA水平较对照组增高，其中ANP24h组TG为（0．81=0．35）mmol／L与对照组差异显著（P〈0．01）；ANP6h组FFA为（1．32—0．32）mmol／IL；较对照组显著升高（P〈0．05）。但ANP组LPL活性较对照组下降，胰腺组织SCDlmRNA和CD36mRNA表达升高。结论 NP大鼠出现血脂增高、脂质代谢相关酶表达异常、胰腺腺泡细胞内质网扩张等方面改变，提示ANP可诱发机体脂质代谢紊乱。     

E-选择素在大鼠急性坏死性胰腺炎肺损伤组织的动态表达及其意义

目的 探讨E-选择素在实验性急性坏死性胰腺炎(ANP)大鼠肺组织的表达及其意义.方法 按随机数字法将大鼠分为对照组及ANP组.采用逆行胆胰管注射5％牛磺胆酸钠制作大鼠ANP模型,术后3、6、12、24 h分批处死动物.检测血清淀粉酶、白蛋白及Ca2+水平,计算肺湿/干重比,常规行胰腺和肺组织病理检查并评分,实时荧光定量PCR及免疫组化法检测大鼠肺组织E-选择素mRNA和蛋白表达.结果 ANP 6 h组大鼠血淀粉酶、胰腺及肺病理评分、肺湿/干重比分别为(3978±476) U/L,(8.22±0.63)分、(12.31 ±1.58)分、5.21 ±0.20、均显著高于对照组的(843±90) U/L、(0.22±0.36)分、(0.13±0.34)分、4.46 ±0.17(P＜0.05或＜0.01);血清白蛋白水平为(12.9±1.0)g/L,显著低于对照组的(15.6 ±0.7)g/L(P ＜0.01);12 h时的血Ca2+水平为( 2.33±0.15)mmoL/L,显著低于对照组的(2.57 ±0.23) mmoL/L(P ＜0.01).E-选择素定位于血管内皮细胞胞膜及胞质.ANP 6 h组大鼠肺组织E-选择素mRNA与蛋白表达显著高于对照组(3.51 ±0.45比0.95 ±0.16;0.174 ±0.019比0.060±0.006,P值均＜0.01).结论 ANP大鼠并发肺损伤时肺组织的血管内皮细胞E-选择素表达呈时间依赖性上调,并参与白细胞的附壁及外渗,促进肺损伤.     

氟伐他汀对心力衰竭患者血清可溶性细胞黏附分子的影响

目的:观察氟伐他汀短期治疗对充血性心力衰竭(congestive heart failure,CHF)患者血清中可溶性细胞间黏附分子-1(sICAM-1)、可溶性血管细胞黏附分子-1(sVCAM-1)、可溶性选择素E(sE- selectin)、可溶性选择素P(sP- selectin)和可溶性选择素L(sL- selectin)水平的影响,探讨氟伐他汀对CHF的治疗作用.方法:将70例CHF患者随机分为常规治疗组和干预组(氟伐他汀组).正常对照组20例.采用酶联免疫吸附法(ELISA)测定其治疗前后血清中sICAM-1、sVCAM-1、sE- selectin、sP- selectin和sL- selectin水平.结果:血清可溶性细胞黏附分子(soluble cell adhesion molecules ,sCAM)水平在心功能Ⅳ级明显高于心功能Ⅱ、Ⅲ级患者,而心功能Ⅱ、Ⅲ级之间比较差异无统计学意义,心功能Ⅱ-Ⅳ级的患者sCAM水平均高于正常对照组(P<0.05或P<0.01).常规治疗组和干预组治疗后血清sCAM水平均较治疗前有显著下降(P<0.05或P<0.01),但干预组较常规治疗组仅sVCAM-1和sE- selectin下降水平显著(P<0.05),余各血清sCAM水平组间比较差异无统计学意义(P>0.05).结论:CHF患者血清sCAM水平下降主要与心功能改善相关,在CHF常规治疗的基础上短期加用氟伐他汀治疗能降低sVCAM-1和sE-selectin水平.     

卡维地洛对不稳定型心绞痛患者血清细胞因子和心肌缺血的影响

目的：探讨卡维地洛对不稳定型心绞痛患者血清细胞因子和心肌缺血的影响。方法：选择100例不稳定型心绞痛患者,分为卡维地洛组和常规治疗对照组（各50例）,测定治疗前后可溶性细胞间粘附分子-1（sICAM-1）和可溶性P-选择素（P-selectin）水平,并观察两组患者治疗前后心肌缺血指标的变化。结果：卡维地洛组和常规治疗对照组患者治疗6个月后血清sICAM-1和可溶性P-选择素水平较治疗前明显降低（P〈0．01,〈0．05）,其中卡维地洛组患者血清sICAM-1和可溶性P-选择素水平降低较对照组更为明显（P均〈0．05）。卡维地洛组和常规治疗对照组患者心绞痛持续时间缩短,ST段下移减轻（P〈0．01,〈0．05）,但卡维地洛组疗效更加明显（P〈0．05）;卡维地洛组的临床疗效总有效率94％,优于常规治疗对照组的72％（P〈0．05）。结论：卡维地洛可以降低不稳定型心绞痛患者血清sICAM-1和可溶性P-选择素水平,抑制冠脉粥样病变的炎症反应,改善心肌缺血症状,是治疗不稳定型心绞痛的理想药物。     

硫氧还蛋白-1在急性坏死性胰腺炎并急性胃黏膜损伤中的作用

目的探讨硫氧还蛋白-1（TRX-1）在实验性急性坏死性胰腺炎（ANP）并急性胃黏膜损伤发病机制中的作用以及抗氧化剂褪黑素对其的影响。方法72只大鼠随机分为对照组（C组,n=24）、ANP组（A组,n=24）和褪黑素干预组（M组,n=24）。A组分3次腹腔内注射6％L-精氨酸（L—Arg）1．5g／kg建立ANP模型;C组同法注射等量生理盐水;M组于首次注射L—Arg前0．5h腹腔内注射1％褪黑素50μg／kg。各实验组大鼠于末次腹腔内注射后6h、12h和24h分批处死。光镜下观察胰腺和胃组织并进行病理学评分,采用免疫组化检测TRX-1在胃黏膜的表达,并检测胃黏膜中MDA、MPO的含量。结果A组各时点胃黏膜TRX-1的染色积分及MDA、MPO的含量明显高于C组（P均〈0．05）;M组各时点胃黏膜中TRX一1的染色积分及MDA、MPO的含量明显低于A组（P均〈0．05）,胰腺和胃组织病理改变较A组明显减轻（P均〈0．05）。结论内源性的TRX-1可能是胃黏膜组织抵御氧化应激损伤的重要因子之一,TRX-1的表达量可能与组织氧化应激损伤的严重程度有关。外源性的褪黑素在ANP时可能通过其抗氧化作用,减轻胃黏膜氧化应激损伤的程度,对胃黏膜有一定的保护作用。     

单核细胞趋化蛋白-1与急性胰腺炎肠屏障功能呈负相关

背景:急性胰腺炎(AP)时可发生全身性炎症反应综合征,肠屏障功能障碍是导致重症急性胰腺炎(SAP)并发多器官功能衰竭的重要因素之一。目的:检测大鼠AP模型单核细胞趋化蛋白-1(MCP-1)表达和肠屏障功能指标的变化,探讨MCP-1在AP肠屏障功能障碍中的作用。方法:分别以0.5%和5%牛磺胆酸钠逆行胰胆管注射制备大鼠急性水肿性胰腺炎(AEP)和急性坏死性胰腺炎(ANP)模型,行胰腺组织病理学评分,电子显微镜观察回肠组织超微结构,免疫组化染色、RT-PCR和蛋白质印迹法检测回肠组织中紧密连接蛋白occludin和MCP-1的表达。结果:与假手术(SO)组相比,AP模型大鼠尤其是ANP组大鼠胰腺组织病理学评分显著升高,回肠绒毛高度和柱状细胞指数降低,occludin表达下调(P0.05)。SO组和AEP组回肠组织中无MCP-1表达,ANP组MCP-1表达随时间延长而上调(P0.05)。回肠组织MCP-1表达与胰腺组织病理学评分呈正相关,与肠屏障功能指标(绒毛高度、柱状细胞指数和occludin表达)呈负相关。结论:ANP大鼠回肠组织中MCP-1表达上调,MCP-1在AP肠屏障功能障碍中发挥重要作用。     

Circulating levels of soluble E-selectin, P-selectin and intercellular adhesion molecule-1 in patients with juvenile idiopathic arthritis

OBJECTIVE: To measure circulating levels of soluble E-selectin (sE-selectin), sP-selectin, and soluble intercellular adhesion molecule-1 (sICAM-1) in patients with active juvenile idiopathic arthritides (JIA), and to evaluate their correlation with disease activity variables and cytokine levels. METHODS: Serum levels of sE-selectin, sP-selectin, and sICAM-1 were measured by ELISA in 42 patients with JIA and in 15 healthy controls. RESULTS: Circulating levels of sE-selectin and sICAM-1, but not sP-selectin, were significantly elevated in patients with active systemic JIA. In patients with active polyarticular or pauciarticular JIA serum levels of sE-selectin. sP-selectin, and sICAM-1 were comparable to those of controls. In patients with systemic JIA, levels of sE-selectin and sICAM-1 were significantly correlated with levels of soluble tumor necrosis factor receptor 2 (sTNFR2), but not with those of interleukin 6 (IL-6) or IL-1beta. CONCLUSION: Patients with active systemic JIA have elevated circulating levels of sE-selectin and sICAM-1. The correlation with sTNFR2, together with previous data on the TNF system in systemic JIA. suggests that TNF activated endothelial cells are the source of sE-selectin and sICAM-1 in this disease.     

A distinct profile of six soluble adhesion molecules (ICAM-1, ICAM-3, VCAM-1, E-selectin, L-selectin and P-selectin) in rheumatoid arthritis

Soluble forms of ICAM-1, VCAM-1, E-selectin, L-selectin, P-selectin and, more recently, ICAM-3 are known to exist in human serum and have elevated levels in numerous diseases. Previous studies have demonstrated that in rheumatoid arthritis (RA) the levels of circulating sICAM-1 and sE-selectin are elevated relative to healthy controls. We have compared the serum profiles of these six soluble adhesion molecules in patients with RA (n = 22) to those seen in healthy controls (n = 10) using sandwich ELISA. In the patients, there were significant elevations of serum sICAM-1 (P < 0.0001), sICAM-3 (P = 0.0327), sVCAM-1 (P = 0.0025), sL-selectin (P = 0.0194) and sP-selectin (P = 0.0025), but not E-selectin (P = 0.0672). However, only sP- selectin was found to correlate with disease activity in the patients (r = 0.461, P < 0.05). Thus, there is a distinct profile of soluble adhesion molecules in RA of which only sP-selectin correlates with disease activity.      

Diurnal variation of soluble E- and P-selectin, and intercellular adhesion molecule-1 in patients with and without coronary artery disease

BACKGROUND: The more frequent onset of acute coronary syndromes (ACS) in the morning has been known for a long time. Diurnal changes of fibrinolysis such as lower activity of tissue plasminogen activator and higher activity of plasminogen activator inhibitor-1 (PAI-1) in the morning has been demonstrated previously and correspond with the manifestation of ACS. Less is known about the diurnal variation of soluble adhesion molecules as markers of endothelial or platelet activity in patients with coronary artery disease (CAD). PATIENTS AND METHODS: 80 patients with a history of myocardial infarction and/or chest pain with positive exercise testing admitted for elective coronary angiography were studied. 10 had normal findings on coronary angiography (control group), 70 patients had at least one or more stenoses >/=50% of the diameter of an epicardial vessel. None of the patients suffered from acute inflammation, connective or tumor disease. Blood samples were drawn at 7:00 a.m. and at 7:00 p.m. at rest and plasma concentration of soluble P-selectin (sP-selectin), E-selectin (sE-selectin), intercellular adhesion molecule-1 (sICAM-1) and acute-phase proteins were measured by ELISA. RESULTS: In both groups, no diurnal variation was found in sE-selectin and sICAM-1. sP-selectin levels were significantly higher in the evening (CAD group: 149.8 +/- 54.5 vs. 172.2 +/- 68.8 ng/ml, p < 0.001; control: 148.7 +/- 75.5 vs. 187.5 +/- 96.3 ng/ml, p = 0.001, Wilcoxon test). CONCLUSION: We have demonstrated diurnal variation of sP-selectin in patients with CAD. We conclude that high sP-selectin values in the evening represent the shed forms of the morning membrane-bound P-selectin.     

复合益生菌制剂对急性坏死性胰腺炎大鼠的保护作用

背景:肠道细菌易位是重症急性胰腺炎(SAP)时胰腺坏死感染的主要来源,因此保护肠黏膜屏障对SAP的治疗具有重要意义。目的:探讨复合益生菌制剂对急性坏死性胰腺炎(ANP)大鼠肠黏膜屏障和胰腺损伤的保护作用。方法:50只SPF级大鼠随机分为假手术组(n=10)、ANP模型组(n=20)和益生菌干预组(n=20)。采用胰腺被膜下均匀注射牛磺胆酸钠制备ANP模型,干预组术前30 min以双歧杆菌四联活菌片溶液灌胃。术后6 h采集标本,检测血淀粉酶、二胺氧化酶(DAO)、TNF-α水平,观察胰腺组织病理学表现和末端回肠组织超微结构。结果:ANP模型组血淀粉酶、DAO、TNF-α水平和胰腺组织学评分均显著高于假手术组(P<0.05),益生菌干预组各项指标均较ANP模型组有所改善(P<0.05)。假手术组末端回肠黏膜结构完整;ANP模型组回肠黏膜上皮细胞微绒毛萎缩、排列稀疏,细胞间连接松弛;益生菌干预组微绒毛稍稀疏,细胞间连接紧密度较ANP模型组增高。结论:复合益生菌制剂对ANP大鼠具有保护作用,不仅能减轻肠黏膜损伤,保护肠黏膜屏障功能,还能减轻胰腺局部损伤和全身性炎症反应。     

Elevated levels of circulating adhesion molecules in patients with active pulmonary tuberculosis

OBJECTIVE: Recent studies have indicated the importance of cell adhesion molecules in the pathogenesis of various inflammatory lung diseases. Our study was designed to determine whether five soluble adhesion molecules including soluble L-, E- and P-selectin (sL-, sE- and sP-selectin), intercellular adhesion molecule-1 (sICAM-1), and vascular cell adhesion molecule-1 (sVCAM-1) in serum reflect the severity of active pulmonary tuberculosis (TB), and whether there is a distinct profile of these soluble molecules in this disease. METHODOLOGY: Using enzyme-linked immunosorbent assays, we measured the serum levels of these five soluble adhesion molecules in 31 patients with active TB and 11 healthy volunteers. RESULTS: Serum levels of sE-selectin, sP-selectin and sICAM-1, but not sL-selectin or sVCAM-1, were significantly higher in patients with active TB than in the control subjects (P < 0.001, each). Significant correlations were detected only between serum levels of sE-selectin and sP-selectin, sE-selectin and sICAM-1, and sP-selectin and sICAM-1. There was a significant correlation between the Gaffky scale result (a scale assessing the number of mycobacteria bacilli present) and all of the above adhesion molecules, except for sL-selectin. Serum levels of sE-selectin, sL-selectin and sICAM-1 also correlated with the CXR radiological score. Higher levels of sL-selectin and sICAM-1 were detected in the serum of patients with radiological cavity formation compared to those without. The ESR, C-reactive protein and circulating neutrophil counts all correlated significantly with sE-selectin, sP-selectin, sICAM-1 and sVCAM-1. CONCLUSION: The results suggest that there is a distinct profile of soluble adhesion molecules in active pulmonary TB and that sE-selectin, sP-selectin, and especially sICAM-1 appear to be the most sensitive clinical measures of disease severity.     

IL-10对急性坏死性胰腺炎大鼠NF—κB及IL-12水平的影响

目的观察白介素10（IL-10）对ANP大鼠NF—κB和IL-12表达的影响，探讨IL-10的作用机制。方法将92只SD大鼠按随机分组法分为对照组、ANP组和IL-10干预组。采用3次腹腔注射左旋精氨酸（1．0mg／g体重）的方法制备ANP模型。对照组腹腔注射等量生理盐水。IL-10组在制模后2、5、8h分别于腹腔内注射IL-10 10 000U。制模后4、12、24、36h分批处死动物，观察血清淀粉酶、IL-12及胰腺组织NF—κB水平的变化。结果制模后24h点IL-10组胰腺病理分值为4．75±1．75，胰腺NF—κB含量为（112．89±34．48）μg/ml，血清淀粉酶含量为（1481．13±336．48）U／L，血清IL-12水平为（81．31±17．23）pg／ml，均明显低于同时点ANP组大鼠（P〈0．05或P〈0．01）。NF—κB和IL-12呈正相关（r=0．494，P〈0．01），两者与胰腺病理分值也呈正相关（r=0．447和r=0．603，P〈0．01）。结论IL-10对ANP有一定的治疗作用，其机能可能通过抑制NF—κB途径而抑制ANP的炎症反应。     

Evaluation of markers of endothelial damage in cases of young myocardial infarction

The pathogenesis of arterial thrombotic disease involves multiple genetic and environmental factors related to atherosclerosis and thrombosis. The endothelium is a monolayer of polygonal cells that extend continuously over the luminal surface of the entire vasculature. Injury to the endothelium leads to dysfunction. The causes of injury include lipids, immune complexes, microorganisms, smoking, hypertension, aging, diabetes mellitus and trauma. Studies have been done to evaluate the role of different adhesion molecules on the endothelial membrane in the pathogenesis of atherosclerosis. These molecules are intercellular adhesion molecule type-1 (ICAM-1), vascular cell adhesion molecule type-1 (VCAM-1), platelet/endothelial cell adhesion molecule-1 (PECAM-1), soluble P-selectin (sP-selectin) and soluble E-selectin (sE-selectin). One-hundred and twenty patients of myocardial infarction (age below 40 years) were recruited from the out-patients department of Department of Cardiology, KEM Hospital, Mumbai. All the patients were recruited 8–10 weeks after stabilization after MI. We estimated the levels of sP-selectin, sE-selectin, sPECAM-1 and serum homocysteine. Healthy age and sex-matched controls and family controls were also recruited in the present study. The levels of sP-selectin, sE-selectin and sPECAM-1 did not differ significantly in cases as compared to controls (p > 0.05). Hyperhomocysteinemia was significantly associated with MI in comparison with controls (p < 0.001) with an odds ratio of 6.26 (95% confidence limits 3.11–12.76). Folic acid was able to correct hyperhomocysteinemia in a large majority of the cases. Although the levels of sP-selectin, sE-selectin and sPECAM-1 decreased after folic acid therapy, it was only sE-selectin which was significantly reduced (p < 0.05). Thus, folic acid had a dual effect in that it reduced hyperhomocysteinemia and sE-selectin which showed a significant reduction on folate supplementation for 15 days.     

PIAS1对重症急性胰腺炎继发急性肺损伤血气屏障影响的研究

背景:研究发现STAT活化抑制蛋白1(PIAS1)可抑制急性坏死性胰腺炎(ANP)继发急性肺损伤,但机制尚不明确。目的:探讨PIAS1对ANP大鼠继发急性肺损伤血气屏障的作用及其机制。方法:构建重组腺病毒Ad5/F35-PIAS1和Ad5/F35-Null质粒。以3.5%牛磺胆酸钠胰胆管逆行注射诱导大鼠ANP模型,并于造模前1 d分别经阴茎静脉注射Ad5/F35-PIAS1、Ad5/F35-Null和PBS液,设立假手术组作为对照。造模16 h后处死大鼠。观察胰腺和肺组织的病理学变化和超微结构改变。测定支气管肺泡灌洗液炎性细胞计数和肺组织湿/干重系数,以免疫组化法检测RECK定位表达,蛋白质印迹法检测肺组织RECK、MMP-2、MMP-9、ICAM-1蛋白表达。结果:与ANP组和Ad5/F35-Null组相比,Ad5/F35-PIAS1组胰腺和肺组织病理学明显改善,肺组织病理学评分显著降低(P<0.01),超微结构示肺泡毛细血管间血气屏障结构破坏减轻;支气管肺泡灌洗液中性粒细胞和巨噬细胞计数、湿/干重系数均显著降低(P<0.01);肺组织RECK蛋白表达显著升高(P<0.01),MMP-2、MMP-9、ICAM-1蛋白表达显著下调(P<0.01);Ad5/F35-PIAS1组上述指标与对照组相比均无明显差异(P>0.05)。结论:PIAS1可能通过增强RECK蛋白表达、抑制MMP-2、MMP-9、ICAM-1蛋白表达,降低血气屏障通透性,抑制炎性细胞外渗,进而改善ANP继发急性肺损伤的炎症程度。