血必净对急性胰腺炎大鼠血清一氧化氮的影响

目的探讨急性胰腺炎(Acute pancreatitis,AP)大鼠血清一氧化氮(Nitric oxide,NO)的变化及血必净注射液对其的影响。方法将90只SD大鼠随机分为假手术组、急性胰腺炎组、血必净组,各组再分为3、6、12 h亚组,假手术组开腹后仅行简单的胰腺翻动,急性胰腺炎组开腹后经十二指肠乳头逆行胆胰管注射5%牛黄胆酸钠建立AP模型,血必净组在AP组基础上予血必净注射液治疗,分别在各时间点采血观察血清中淀粉酶(AMY)、一氧化氮(NO)的变化,并进行胰腺组织病理学检查。结果与假手术组相比,AP组中AMY、NO浓度明显增高,差异有统计学意义(P<0.05);与AP组相比,血必净组中AMY、NO浓度明显降低,差异有统计学意义(P<0.05),光镜下AP组胰腺组织损伤明显,而血必净组损伤明显改善。结论 NO参与急性胰腺炎的发生发展过程,血必净注射液能显著降低血清NO,减轻胰腺组织的损伤。     

血必净对急性胰腺炎血液流变学的影响

目的观察血必净注射液对急性胰腺炎（AP）患者血液流变学的影响。方法将59例AP患者随机分为治疗组（n=30）和对照组（n=29）,治疗组在常规西医治疗的基础上加用血必净注射液,对照组仅采用西医常规治疗;检测治疗前及治疗后7d两组患者血液流变学指标。结果经过7d的治疗,治疗组结果如下：全血粘度（高切）：（3．50±0．24）mPa·s;全血粘度（低切）：（7．34±0．25）mPa·s;还原粘度（高切）：（6．80±0．95）mPa·s;还原粘度（低切）：（19．01±2．45）mPa·s;血沉：（22．40±3．59）mm／h;血浆粘度：（1．25±0．07）mPa·s;红细胞聚集指数：（2．10±0．23）。治疗组结果与治疗前以及对照组存在显著性差异（P〈0．05）。结论血必净注射液能有效改善AP患者血液流变学异常。     

血必净治疗急性胰腺炎36例临床研究

目的 探讨血必净注射液对急性胰腺炎患者的治疗效果.方法 将82例急性胰腺炎患者随机分为血必净治疗组和常规治疗组,常规治疗组接受改善胰周循环、抑酸、抑酶、抗炎治疗,血必净组在上述常规治疗基础上+血必净注射液40ml静点,1次/d.监测两组患者体征缓解时间、血尿淀粉酶变化情况.结果 两组体征缓解时间上无明显差异(P＞0.0...     

血必净治疗急性胰腺炎的临床疗效及对血清氧自由基的影响

目的探讨血必净治疗急性胰腺炎的临床疗效以及对血清丙二醛（MDA）、超氧化物歧化酶（sOD）水平的影响。方法选取符合标准的患者60例,随机分为观察组和对照组各30例,两组患者均给予常规治疗,观察组加用血必净注射液,比较二者临床疗效和血清MDA、SOD水平。结果两组患者入院时血清MDA、SOD水平相似,差异无统计学意义衅（P〈0．05）;治疗7d后,两组患者血清MDA水平均下降、SOD均上升,但观察组改善幅度较对照组显著,差异有统计学意义（P〈0．05）。观察组患者临床总有效率80．00％,明显高于对照组的63．33％,差异有统计学意义（P〈O．05）。结论血必净治疗急性胰腺炎,可有效清除氧自由基,提高临床治疗效果,促进患者康复。     

血必净注射液综合治疗重症急性胰腺炎疗效观察

目的:观察血必净注射液治疗重症急性胰腺炎(SAP)的疗效及毒副作用。方法:将65例SAP患者随机分为观察组和对照组。2组均给予常规治疗,观察组加用血必净注射液静脉滴注。观察2组腹痛和腹胀及恶心呕吐消失时间、白细胞和血淀粉酶恢复正常时间、临床疗效、并发症和毒副作用。结果:观察组总有效率、痊愈率明显高于对照组(P<0.01或P<0.05),并发症明显低于对照组(P<0.01);腹痛、腹胀及恶心呕吐消失时间,体温恢复正常时间,白细胞、血淀粉酶恢复正常时间显著短于对照组(P<0.01或P<0.05)。结论:血必净注射液可作为SAP综合治疗中的常规临床用药。     

血必净注射液辅助治疗急性重症胰腺炎的疗效观察

目的:观察血必净注射液辅助治疗急性重症胰腺炎的疗效。方法:选择急性重症胰腺炎患者80例,按随机数字表法分为对照组和观察组,各40例。对照组患者采用对症支持处理,观察组患者在对照组的基础上加用血必净注射液静脉滴注,每次100ml,每天2次。比较治疗前后两组患者肿瘤坏死因子α(TNF-α)、白细胞介素6(IL-6)和超敏C反应蛋白(hs-CRP)的水平,以及器官衰竭情况。结果:治疗前两组患者TNF-α、IL-6和hs-CRP水平差异无统计学意义(P>0.05);治疗后观察组患者的TNF-α、IL-6和hs-CRP水平均显著低于对照组及治疗前,差异均有统计学意义(P<0.05)。观察组患者发生肾功能、呼吸功能与循环功能衰竭的比例均显著低于对照组,差异有统计学意义(P<0.05)。结论:急性重症胰腺炎患者在对症治疗中加用血必净注射液能显著降低机体炎症水平,减少对器官功能的损伤。     

血必净注射液治疗重症急性胰腺炎的临床疗效观察

目的:观察血必净注射液治疗重症急性胰腺炎(SAP)的临床疗效。方法:将65例SAP患者随机分为2组:对照组30例,采用规范化西医综合治疗;治疗组35例,在对照组治疗方法的基础上加用血必净注射液静脉滴注,每次100mL,每日1次。2组疗程均为7d。结果:治疗组总有效率为94.3%,对照组为83.4%,2组之间比较具有显著性差异(P<0.05);2组并发症发生率具有显著性差异(P<0.05);2组观察指标变化情况比较具有显著性差异(P<0.01或P<0.05)。结论:血必净注射液可作为SAP综合治疗中的常规辅助用药。     

血必净注射液治疗急性胰腺炎的Meta分析

目的：评价血必净对急性胰腺炎患者血浆内皮素浓度的影响,从而了解血必净对微循环的改善作用及用于辅助治疗急性胰腺炎的临床疗效。方法：计算机检索结合手工筛选,选择符合纳入标准的中文随机或临床对照试验（CRT、CCT）文献,对数据进行Meta分析。结果：8项研究包括567例患者,经Meta分析显示,血必净注射液治疗组患者血浆内皮素浓度与对照组比较[OR=-27.72,95%CI（-40.64,-14.80）,P〈0.000 1],血淀粉酶恢复正常时间[OR=-2.61,95%CI（-3.01,-2.20）,P〈0.000 01],腹痛缓解消失时间[OR=-1.80,95%CI（-2.21,-1.38）,P〈0.000 01],平均住院日数[OR=-4.66,95%CI（-7.02,-2.31）,P=0.000 1]有统计学差异。结论：现有研究结果表明,治疗组与对照组比较应用血必净注射液治疗急性胰腺炎,患者血浆内皮素浓度明显降低,治疗组能显著减少急性胰腺炎患者腹痛缓解消失时间和血淀粉酶复常时间。且治疗组患者平均住院日数也相应缩短。     

ICAM-1在大鼠急性胰腺炎肺损伤中的作用

目的：探讨ICAM-1在大鼠急性胰腺炎（acute pancreatitis,AP）肺损伤中的作用。方法：雄性Wistar大鼠40只,随机分为对照组（CON组）、AP不同时间点（3,6,12h）组。胆胰管逆行注射5％牛磺胆酸钠制备急性胰腺炎模型,术后3,6,12h分批剖杀大鼠,每个时间点10只。观察肺组织病理学改变并评分,检测血清淀粉酶（AMY）、肺组织髓过氧化物酶（MPO）活性;逆转录聚合酶链反应（RT—PCR）检测肺组织肿瘤坏死因子-α（TNF-α）和细胞间黏附分子-1（ICAM-1）mRNA表达;Western Blot法检测肺组织中ICAM-1蛋白表达。结果：AP组各时间点AMY、MPO和肺组织病理评分均较CON组升高（P〈0．05）;TNF-α和ICAM-1mRNA表达逐渐升高,均12h达到高峰;同时ICAM-1蛋白表达也逐渐升高,并在12h达到高峰。结论：AP大鼠肺组织中,ICAM-1在mRNA和蛋白水平均呈过度表达,且与肺损伤的严重程度密切相关。前炎症因子TNF-α在肺组织中ICAM-1的过度表达起着重要作用。     

血必净注射液对重症急性胰腺炎疗效及患者细胞免疫功能的影响

目的探讨血必净注射液对重症急性胰腺炎(SAP)的临床疗效及对患者细胞免疫功能的影响。方法 64例SAP患者随机分为两组,每组各32例,对照组进行常规治疗,试验组在此基础上加用血必净注射液100 m L静脉滴注,bid,7 d为一个疗程。观察临床症状、实验室指标恢复正常的时间,统计中转手术率、病死率,并观察并发症发生情况。治疗前后评估APACHEⅡ评分,检测T淋巴细胞亚群、NK T淋巴细胞水平。结果对照组中转手术治疗3例,试验组1例。与对照组相比,试验组体温、血及尿淀粉酶恢复正常时间、腹痛腹胀消失时间、首次排便时间和病程均缩短(P<0.05)。治疗后,两组患者APACHEⅡ评分均下降(P<0.05),CD4+T细胞、CD8+T细胞、CD4+/CD8+及NK T细胞水平均增高(P<0.05),试验组改善幅度大于对照组(P<0.05)。对照组并发症发生率(28%,9/32)高于试验组(6%,2/32,P<0.05),对照组死亡1例,试验组无。结论常规治疗基础上加用血必净注射液,可改善SAP患者临床症状和实验室指标、缩短病程、减少并发症发生,增强患者细胞免疫功能可能为其作用机制之一。     

外周血LFA-1和ICAM-1在非小细胞肺癌中的临床意义及表达

目的：探讨非小细胞肺癌血清中LFA-1和ICAM-1的表达在肿瘤侵袭转移过程中的作用机制。方法：采用双抗体夹心ABC-ELISA法测定。结果：（1）非小细胞肺癌患者血清中LFA—1和ICAM-1的含量明显高于对照组;差异具有显著性（P〈0．01）;（2）非小细胞肺癌患者LFA-1和ICAM-1间存在正相关性（P〈0．05）。（3）肺癌的I＋N期与I＋Ⅱ期相比血清LFA-1、ICAM-1均有显著差异（P〈0．05）。（4）有淋巴结转移者血清LFA-1和1CAM-1含量较无淋巴结转移者增高,差异显著（P〈0．05）。结论：LFA-1 ICAM-1可能是反映肺癌侵袭转移潜能的一个有效生物学指标。     

砷剂治疗急性早幼粒细胞白血病高白细胞期LFA-1,Mac-1和ICAM-1

目的 :观察三氧化二砷 (As2 O3)和维甲酸 (ATRA)治疗急性早幼粒细胞白血病 (APL )患者高白细胞发生后 ,黏附分子 L FA- 1(淋巴细胞功能相关抗原 - 1)和 Mac- 1以及细胞间黏附分子 - 1(ICAM- 1)的表达。方法 :随机分两组 ,分别选用 0 .1% As2 O310 m L / d,静脉点滴 ;ATRA 2 5 mg· m- 2 · d- 1 ,分 3次口服。分别用流式细胞仪观察两组治疗前及治疗后白细胞增高期外周血白细胞上 L FA - 1和 Mac- 1的表达及其培养上清刺激内皮细胞 ICAM- 1的表达。结果 :As2 O3组和 ATRA组治疗后高白细胞时 L FA - 1分别为 (5 1.87± 17.6 5 ) %和 (4 8.32± 16 .98) % ,Mac- 1分别为 (4 5 .2 5± 19.12 ) %和 (4 3.4 5± 2 0 .6 5 ) % ,明显高于治疗前 ,两组间无明显差别。As2 O3组和 ATRA组高白细胞期 APL骨髓上清刺激内皮细胞表达 ICAM- 1增加分别为 (6 9.39± 18.4 6 ) %和 (6 4 .5 7± 7.2 4 ) % ,明显高于治疗前 (4 2 .35± 9.36 ) %和 (4 5 .5 6± 6 .86 ) %。结论 :As2 O3和 ATRA治疗 APL高白细胞的发生与诱导分化治疗过程中 APL细胞的黏附分子 L FA- 1和 Mac- 1表达增加 ,并刺激内皮细胞 ICAM- 1的增加有关 ,L FA - 1,Mac- 1和ICAM- 1互相作用 ,使 APL细胞与内皮细胞黏附增加 ,并释放入外周血增加。     

Mechanism of Binding and Internalization of ICAM-1-Derived Cyclic Peptides by LFA-1 on the Surface of T Cells: A Potential Method for Targeted Drug Delivery

Purpose. Peptides derived from the Domain 1 of the adhesion molecule ICAM-1_1-21 are being developed as targeting ligands for LFA-1 receptors expressed on activated T cells. This work aims to elucidate the binding and internalization of ICAM-1-derived cyclic peptides (cIBL, cIBC, and cIBR) to LFA-1. Methods. Ninety-six-well plates coated with soluble LFA-1 (sLFA-1) were used to characterize the binding of FITC-labeled peptide. An anti-CD11a antibody to the I-domain of LFA-1 was used to inhibit the binding of these peptides, which was quantified using a fluorescence plate reader. An unrelated FITC-labeled cyclic peptide was used as a negative control, and PE-labeled anti-CD11a antibodies (PE-R3.2 and PE-R7.1) were used as positive controls. Peptide binding to cell surface LFA-1 was visualized using colocalization of FITC-cIBR peptide and PE-labeled anti-CD18 antibody (LFA-1 -subunit) on SKW-3 T cells by fluorescent microscopy. Inhibition of ICAM-1 binding to LFA-1 by peptides was evaluated using a Biacore assay. Binding and internalization of FITC-labeled peptides were evaluated by flow cytometry and confocal microscopy at 4°C and 37°C. Results. These FITC-labeled cyclic peptides bind to sLFA-1 and can be blocked by an anti-CD11a antibody to the I-domain, suggesting that their binding site is on the I-domain of LFA-1. The FITC-cIBR peptide was localized with an anti-CD18 antibody on the surface of T cells, indicating that the FITC-cIBR peptide binds to LFA-1 on the cell surface. Flow cytometry and confocal microscopy demonstrated that FITC-labeled peptides were internalized in a temperature-dependent manner. Biacore analysis demonstrated that these peptides did not inhibit sICAM-1 from binding to immobilized sLFA-1. However, the binding properties of the soluble forms of LFA-1 and ICAM-1 may not correlate to their interaction at the cell surface. Conclusions. Cyclic ICAM-1-derived peptides (cIBL, cIBC, and cIBR) bind to the I-domain of LFA-1 and are internalized by LFA-1 receptors on the surface of T cells. Therefore, these peptides could be used to target and deliver drugs to the cytoplasmic domain of T cells.     

Small molecule antagonists of the LFA-1/ICAM-1 interaction as potential therapeutic agents

The interaction between leukocyte function-associated antigen-1 (LFA-1), a member of β₂ integrin family, and intracellular adhesion molecule-1 (ICAM-1) plays a critical role in mediating cell adhesion, leukocyte transmigration and augmentation of T-cell receptor signalling. Small molecule antagonists of LFA-1/ICAM-1 represent a new therapeutic area for treatment of diseases such as psoriasis, rheumatoid arthritis and ischaemic reperfusion injury. The rapid development of this field is evidenced by the increasing numbers of patents filed and numbers of promising preclinical compounds which have emerged in recent years. Most patents claiming LFA-1/ICAM-1-mediated adhesion inhibitors between January 1999 and April 2001 concerned small molecule inhibitors. This review focuses on the novel composition of matter patents in the area of small molecule LFA-1/ICAM-1 interaction antagonists. The mechanism of action for some molecules that inhibit this set of protein-protein interaction will also be discussed.     

Calendula officinalis ameliorates l-arginine-induced acute necrotizing pancreatitis in rats

Context: Calendula officinalis L. (Asteraceae) has been traditionally used in treating inflammation of internal organs, gastrointestinal tract ulcers and wound healing.

Objective: The present study investigates the effect of ethanol extract (95%) of Calendula officinalis flowers in l-arginine induced acute necrotizing pancreatitis in rats.

Materials and methods: Rats were divided into four groups: normal control, l-arginine control, Calendula officinalis extract (COE) treated and melatonin treated (positive control), which were further divided into subgroups (24?h, day 3 and 14) according to time points. Two injections of l-arginine 2?g/kg i.p. at 1?h intervals were administered in l-arginine control, COE and melatonin-treated groups to produce acute necrotizing pancreatitis. Biochemical parameters [serum amylase, lipase, pancreatic amylase, nucleic acid content, total proteins, transforming growth factor-β1 (TGF-β1), collagen content, lipid peroxidation, reduced glutathione and nitrite/nitrate] and histopathological studies were carried out.

Results: COE treatment (400?mg/kg p.o.) was found to be beneficial. This was evidenced by significantly lowered histopathological scores (2 at day 14). Nucleic acid content (DNA 21.1 and RNA 5.44?mg/g pancreas), total proteins (0.66?mg/mL pancreas) and pancreatic amylase (1031.3 100 SU/g pancreas) were significantly improved. Marked reduction in pancreatic oxidative and nitrosative stress; collagen (122 μmoles/100?mg pancreas) and TGF-β1 (118.56?pg/mL) levels were noted. Results obtained were comparable to those of positive control.

Discussion and conclusion: The beneficial effect of COE may be attributed to its antioxidant, antinitrosative and antifibrotic actions. Hence, the study concludes that COE promotes spontaneous repair and regeneration of the pancreas.     

苦参素对实验性自身免疫性脑脊髓炎大鼠MMP-9、ICAM-1、HO-1表达的影响

目的: 通过检测实验性自身免疫性脑脊髓炎(EAE)模型脊髓中MMP-9、ICAM-1、HO-1的mRNA表达来研究苦参素对EAE的治疗作用。方法: 选取40只大鼠随机分为EAE组、空白对照组、苦参素低剂量组和苦参素高剂量组。EAE组和苦参素两个剂量组注射豚鼠全脊髓匀浆(GPSCH)抗原乳剂免疫建立EAE模型。苦参素两个剂量组于免疫当天起鼠尾静脉注射苦参素注射液200 mg·kg^-1和100 mg·kg^-1。观察3组大鼠的发病情况, 采用5分评分法对症状进行评分。设计和合成三条针对MMP-9、ICAM-1、HO-1mRNA的特异性引物, 采用PCR技术检测苦参素治疗16 d后大鼠脊髓中MMP-9、ICAM-1、HO-1mRNA的表达。结果: EAE组平均症状评分(2.45±0.36)高于苦参素治疗组(1.35±0.21), 且两者之间存在显著性差异(P<0.05)。与空白对照组比较, EAE组大鼠脊髓中MMP-9、ICAM-1的表达显著升高(P<0.01), 而苦参素治疗组中MMP-9、ICAM-1的表达与EAE组比较有所降低(P<0.05)。与空白对照组比较, EAE组大鼠脊髓中HO-1的表达显著降低(P<0.05), 而苦参素治疗组中HO-1的表达显著升高(P<0.01)。结论: 苦参素能够通过降低MMP-9和ICAM-1mRNA的表达, 并促进HO-1mRNA的表达而发挥对实验性自身免疫性脑脊髓炎的治疗作用。     

Discovery and Development of Potent LFA-1/ICAM-1 Antagonist SAR 1118 as an Ophthalmic Solution for Treating Dry Eye

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Structural recognition of an ICAM-1 peptide by its receptor on the surface of T cells: conformational studies of cyclo (1, 12)-Pen-Pro-Arg-Gly-Gly-Ser-Val-Leu-Val-Thr-Gly-Cys-OH

Abstract: The purpose of this study is to elucidate the solution conformation of cyclic peptide 1 (cIBR), cyclo (1, 12)-Pen1-Pro2-Arg3-Gly4-Gly5-Ser6-Val7-Leu8-Val9-Thr10-Gly11-Cys12-OH, using NMR, circular dichroism (CD) and molecular dynamics (MD) simulation experiments. cIBR peptide ( 1 ), which is derived from the sequence of intercellular adhesion molecule-1 (ICAM-1, CD54), inhibits homotypic T-cell adhesion in vitro. The peptide hinders T-cell adhesion by inhibiting the leukocyte function-associated antigen-1 (LFA-1, CD11a/CD18) interaction with ICAM-1. Furthermore, Molt-3 T cells bind and internalize this peptide via cell surface receptors such as LFA-1. Peptide internalization by the LFA-1 receptor is one possible mechanism of inhibition of T-cell adhesion. The recognition of the peptide by LFA-1 is due to its sequence and conformation; therefore, this study can provide a better understanding for the conformational requirement of peptide–receptor interactions. The solution structure of 1 was determined using NMR, CD and MD simulation in aqueous solution. NMR showed a major and a minor conformer due to the presence of cis/trans isomerization at the X-Pro peptide bond. Because the contribution of the minor conformer is very small, this work is focused only on the major conformer. In solution, the major conformer shows a trans-configuration at the Pen1–Pro2 peptide bond as determined by HMQC NMR. The major conformer shows possible β-turns at Pro2-Arg3-Gly4-Gly5, Gly5-Ser6-Val7-Leu8, and Val9-Thr10-Gly11-Cys12. The first β-turn is supported by the ROE connectivities between the NH of Gly4 and the NH of Gly5. The connectivities between the NH of Ser6 and the NH of Val7, followed by the interaction between the amide protons of Val7 and Leu8, support the presence of the second β-turn. Furthermore, the presence of a β-turn at Val9-Thr10-Gly11-Cys12 is supported by the NH–NH connectivities between Thr10 and Gly11 and between Gly11 and Cys12. The propensity to form a type I β-turn structure is also supported by CD spectral analysis. The cIBR peptide ( 1 ) shows structural similarity at residues Pro2 to Val7 with the same sequence in the X-ray structure of D1-domain of ICAM-1. The conformation of Pro2 to Val7 in this peptide may be important for its binding selectivity to the LFA-1 receptor.     

益生菌对急性坏死性胰腺炎大鼠的保护作用研究

目的观察益生菌对急性坏死性胰腺炎大鼠的保护作用,并对其作用机理进行探讨。方法 SD大鼠120只,随机分为假手术组、急性坏死性胰腺炎模型组以及大、小剂量益生菌治疗组。大鼠急性坏死性胰腺炎模型是经胆胰管逆行注射5%牛磺胆酸钠形成,益生菌制剂成分为双歧杆菌、乳杆菌和嗜热链球菌。益生菌经灌胃途径预防给药,于造模前3d起,每天给药1次,连续给药3d。分别于造模后6h、12h取血,测定血清淀粉酶、TNF-α和IL-6水平,观察各组动物48h死亡率。结果益生菌能明显降低急性坏死性胰腺炎大鼠48h死亡率,降低血清淀粉酶、TNF-α和IL-6水平。结论益生菌通过抑制炎症因子的表达,对急性坏死性胰腺炎起到保护作用。     

祛瘀化痰法对哮喘大鼠血管内皮细胞黏附分子及白介素12表达的影响

目的研究蠲哮汤对哮喘大鼠血管内皮细胞黏附分子（ICAM-1）及白介素12（IL-12）表达的影响。方法建立由卵蛋白诱发的支气管哮喘大鼠模型;采用ELISA法检测哮喘大鼠静脉血和肺泡灌洗液（BALF）中ICAM-1、IL-12的含量。结果模型组ICAM-1高表达,IL-12低表达,蠲哮汤能减少造模动物ICAM-1的表达,提高IL-12的表达。结论蠲哮汤能减少造模动物ICAM-1,提高IL-12的表达,而且随着药物剂量的减少,各分表达呈递增趋势,具有量效关系。