P-选择素与心肌缺血再灌注损伤

本文就P-选择素参与心肌缺血再灌注损伤病理过程及抗P-选择素治疗在动物模型中减轻心肌缺血再灌注损伤的研究进行综述.     

BQ123对大鼠肢体缺血再灌注后肺P-选择素表达的影响

目的 观察大鼠肢体缺血再灌注后肺组织P-选择素表达的变化及内皮素A受体阻断剂BQ123对其影响.方法 雄性Wistar大鼠随机分为3组（n=10）：对照组、再灌注组和BQ123处理组.缺血4h再灌注4h后采用ELISA方法定量检测肺P-选择素浓度,测定各组PaO2、BALF蛋白含量,测定肺组织髓过氧化物酶、内皮素1的含量,观察肺组织病理变化.结果 与再灌注组比较,BQ123处理组肺组织P-选择素含量明显降低,PaO2升高,BALF中总蛋白、肺组织髓过氧化物酶、内皮素1明显降低（P值均＜0.01）,肺组织形态损伤减轻.结论 BQ123抑制了大鼠肢体缺血再灌注后肺组织P-选择素的表达,减轻肺损伤.     

P-选择素与心肌缺血再灌注损伤

:在急性心肌梗塞血管内溶栓、经皮冠状动脉内成形术、体外循环等治疗过程中 ,患者面临心肌缺血再灌注 (ischemia/reperfusion;I/ R)损伤问题。心肌 I/ R损伤涉及多种因素 ,包括氧自由基产生、Ca2 超负荷、血管活性物质释放、中性粒细胞的浸润 ,尤其是后者 ,因它与活化血小板、内皮细胞的相互作用 ,经级联 (cascade)反应产生大量酶、氧自由基及形成血栓 ,在心肌 I/ R损伤中起关键作用。而 P-选择素 (P- selectin;Ps)是这一系列事件的始动条件 ,因此对 Ps进行深入研究 ,对于揭示心肌 I/ R损伤机制 ,防治临床上心肌 I/ R损伤 ,具有重要意义。     

血管活性肠肽对脑缺血再灌注损伤模型大鼠P-选择素的影响

目的 通过活体实验研究体外注射血管活性肠肽(VIP)对脑缺血再灌注损伤模型大鼠P-选择素动态变化的影响,探讨VIP在缺血再灌注炎症损伤中的神经保护作用.方法 模型组大鼠侧脑室注射VIP后,用线栓法制作大鼠大脑中动脉再灌注(MCAO)模型.通过神经学的评价对MCAO大鼠进行判定和筛选;选取再灌注后12 h、24 h、48 h和72 h共4个时间点,采用原位杂交法检测P-选择素mRNA的表达;应用免疫组化检测P-选择素蛋白表达.结果 模型组大鼠VIP注射后P-选择素mRNA和蛋白在脑缺血再灌注后较对照组表达下降;且在各时间点与非VIP注射的对照组比较差异具有统计学意义(P<0.05).结论 VIP脑内注射可明显降低脑缺血再灌注后缺血区P-选择素mRNA和蛋白的表达,降低再灌注炎症损伤程度.本实验提示VIP具有体外神经保护作用.     

黄芪对大鼠肝缺血再灌注损伤的影响

目的 探讨黄芪对大鼠肝缺血再灌注损伤的影响,以及与缺血预处理(IP)作用效果的比较.方法 清洁级健康雄性SD大鼠96只,随机分为假手术组、缺血再灌注组(IR组)、缺血预处理组(IP组)、黄芪组,每组又按再灌注时间(1、3、6、24 h)分为4个时相,每组各时相为6只.制作70%肝缺血再灌注模型,测血清谷丙转氨酶(ALT)、谷草转氨酶(AST)、乳酸脱氢酶(LDH)水平;测肝组织髓过氧化物酶(MPO)含量;用免疫组化法检测IL-10、TNF-α表达;以及光镜及电镜观察大鼠肝形态学变化.结果 IR、IP、黄芪组ALT、AST、LDH和MPO含量均明显高于假手术组(P<0.01).与IR组相比,IP、黄芪组各个时相点的值均下降(P<0.05).与IP组比较,黄芪组各个时相点的值均降低(P<0.05).IR、IP、黄芪组肝组织TNF-α、IL-10的阳性细胞表达率均比假手术组高(P<0.05);与IR组比较,IP、黄芪组TNF-α的表达减少,而IL-10的表达增强(P<0.05);与IP组比较,黄芪组TNF-α的表达减少,IL-10表达增强(P<0.05).在光镜及电镜下观察肝形态学变化,可见IR组损伤甚为明显,IP及黄芪组损伤程度较IR组轻,黄芪组更轻,而假手术组肝形态正常.结论 IP和黄芪都可减轻缺血再灌注对肝脏的损伤,且后者较前者效果好.     

P选择素和E选择素在肝缺血再灌注损伤中的作用

研究发现,黏附分子家族的Ca2＋依赖外源凝集素一族--P选择素和E选择素,在感染、创伤、缺血再灌注等病理生理过程中,特别是在炎症早期发展过程中起重要作用［1］。肝脏缺血再灌注损伤（IRI）在严重肝外伤、肝叶部分切除（肝门阻断）、肝移植等过程中均可发生,处理方法包括缺血预处理、麻醉处理、药物预处理等。研究肝脏缺血再灌注中P选择素、E选择素的表达规律及其与肝脏损伤的关系,对于选择合理的治疗时机及改善肝脏IRI有重要意义。现将P选择素、E选择素在肝脏IRI中的作用综述如下。     

心肌缺血再灌注对大鼠P-选择素表达的影响及硫酸镁的作用

心肌缺血再灌注损伤(IR)被认为可能与血小板、白细胞、血管内皮细胞以及心肌细胞的相互作用有关,细胞黏附分子在其间发挥重要作用。有研究表明,抑制黏附分子P选择素(Ps)、CD11b的表达可减少心肌IR损伤。本研究观察了心肌缺血再灌注期间大鼠内皮细胞、血小板及心肌组织Ps表达的变化及硫酸镁的作用。一、材料与方法1.建立在体大鼠心肌缺血再灌注模型:选240～280g雄性SD大鼠,随机分成4组:A组(对照组,n=6),不对动物作任何处理;B组(假手术组,n=30),术中仅在冠状动脉前降支(LAD)下穿线而不结扎,余操作同C组;C组(IR组,n=30),在LAD下穿线…     

链激酶对大鼠肝脏缺血再灌注损伤的保护作用

目的:研究链激酶对大鼠肝脏缺血再灌注损伤的保护作用.方法:36只Wistar大鼠随机分成3组,每组12只.对照组大鼠肝脏经门脉10 mL乳酸林格液灌洗后,低温4℃UW液中保存24h.实验组大鼠肝脏经含链激酶7500 IU乳酸林格灌洗后,分别低温或低温静脉持续氧气灌注保存24 h后.离体常温再灌注45 min,观察灌洗液谷氨酰胺丙氨酸转氨酶(alanine aminotransferase.ALT)、谷氨酸乳酸脱氢酶(glutamate-lactate dehydrogenase,GLDH)和嘌呤核苷磷酸化酶(purine nucleoside phosphorylase,PNP)活性及肝脏胆汁分泌量、肝组织5'核苷酸酶活性的变化.结果:实验组再灌注过程中灌洗液ALT、GLDH和PNP活性均明显降低于对照组(P＜0.05或P＜0.01);胆汁分泌量增加[3.7±0.7μL/(g·45 min),9.1±0.μL/(g·45 min)vs1.1±0.9μL/(g·45 min),P＜0.05,P＜0.01);5'核苷酸酶活性染色明显增强.结论:链激酶改善低温保存肝脏的微循环,减轻缺血再灌注损伤.     

肝缺血再灌注损伤时乳酸脱氢酶活性的变化和川芎嗪的保护作用

目的:探讨肝缺血再灌注损伤(HIRI)时乳酸脱氢酶(LDH)活性的改变及川芎嗪的保护作用.方法:制备 HIRI模型,随机将21只家兔分为三组(对照组,7只;盐水组,7只;川芎组,7只),观察血清及肝组织LDH活性的动态变化及川芎嗪对它们的影响.结果:盐水组血清LDH活性进行性升高,肝组织LDH则明显下降;川芎组变化不明显,血清及肝组织LDH活性与盐水组比较,均有显著性差异.结论:川芎嗪对HIRI时LDH活性的异常改变有明显的保护作用.     

P-选择素与心肌缺血再灌注损伤及其单克隆抗体的应用研究

选择素(selectin)是一种细胞粘附分子，通过介导多形核白细胞与冠状血管内皮细胞之间粘附，对缺血心肌产生再灌注损伤。目前，应用其单克隆抗体的治疗正逐步显示出它的重要性，并将逐步从实验研究走向临床应用。     

Kupffer细胞与肝缺血再灌注损伤

Kupffer细胞作为肝脏固有巨噬细胞在炎症反应及肝脏缺血再灌注损伤中发挥重要作用.Kupffer细胞激活后将诱发TNF-α、前列腺素、一氧化氮及氧自由基等各种炎症细胞因子的大量形成,除导致自身功能形态发生改变外,还直接影响邻近的肝细胞、血管内皮细胞以及位于血窦腔内的中性粒细胞等多种细胞,进而启动热缺血或冷缺血后肝脏的缺血再灌注损害.现就Kupffer细胞在肝脏缺血再灌注损伤中的作用机制及对其治疗靶点研究进展作一综述.     

Protective effects of HGF-MSP chimer (metron factor-1) on liver ischemia-reperfusion injury in rat model

OBJECTIVE: It has been reported that metron factor-1 (MF-1), an engineered chimerical factor containing selected functional domains of hepatocyte growth factor and macrophage-stimulating protein (HGF–MSP), could prevent apoptosis and have an anti-inflammatory effect. In this study, we investigate the protective effect of MF-1 on liver ischemia-reperfusion (I/R) injury. METHODS: Overall 30 Sprague Dawley rats were randomly divided into three groups: the I/R model group (n = 12), the MF-1 treatment group (n = 12), and the sham-operated group (n = 6). Liver I/R injury was induced by clamping the blood supply to the left and median lobes of liver by an atraumatic clamp for 90 min, then removing the clamp and allowing reperfusion. Blood samples were obtained on days 1, 2, 3 and 7 to assess liver biochemistry and the histology of liver tissue. Levels of malondialdehyde (MDA), superoxide dismutase (SOD), nitric oxide (NO), endothelial nitric oxide synthase and inducible nitric oxide synthase were measured. In addition, the anti-oxidative effect of MF-1 on hepatocytes was assessed in vitro. RESULTS: MF-1 treatment improved the rat survival rate significantly (P < 0.05). Liver biochemistry and histological changes were significantly ameliorated. MDA increased and SOD and NO decreased in the liver tissue. In vitro, MF-1 protected the human hepatic cell line HL-7702 from damage of oxidative stress. CONCLUSION: MF-1 could protect the liver from I/R injury, which might involve the reduction of oxygen free radicals and the increase of NO synthesis in an injured liver.     

川芎嗪对脑缺血——再灌注大鼠神经功能及神经电生理的影响

目的观察腹腔注射川芎嗪对脑缺血—再灌注大鼠神经功能及神经电生理的影响。方法将20只大鼠随机分为A、B组,制作大鼠大脑中动脉栓塞模型后,分别腹腔注射生理盐水及川芎嗪80mg／kg,2次／d,连用7d。采用双盲法行大鼠神经功能评分,采用TTC染色法测量大鼠脑梗死灶体积,并行运动诱发电位检测。结果A组神经功能评分为（3．31±0．23）分,脑梗死灶体积为（45．63±12．75）mm^3,运动阈值为52．67％±8．75％,B组分别为（2．30±0．15）分、（26．59±7．64）mm^3、34．29％±5．18％,P均〈0．05。损伤后的运动阈值与脑梗死灶体积呈正相关（r=0．68,P〈0．05）。结论川芎嗪可减小缺血—再灌注损伤脑组织梗死灶体积,提高皮质兴奋性。     

丹参川芎嗪注射液对肺栓塞大鼠P-选择素及组织因子的影响

目的:通过观察肺栓塞大鼠用药后血中P-选择素(CD62P)及组织因子(TF)的变化,研究丹参川芎嗪注射液、低分子肝素及两者联合应用对肺栓塞大鼠的影响。方法:健康雄性Wistar大鼠80只,随机分为7 h组及1周组,每组又分为对照组、栓塞组、丹参川芎嗪组、低分子肝素组、联合用药组,每小组8只大鼠。将大鼠分离右侧颈静脉,对照组注射生理盐水,其余各组注入自制栓子(25±3)个(约0.5 mm/个)。各组在第7小时及第7天采血,检测TF及CD62P浓度,并观察肺组织。结果:栓塞后大鼠可见喘憋、发绀、心率加快等,肺组织可见表面凹凸不平,膨胀不均,散在灰白色梗死区域。栓塞组与对照组相比,血浆中TF、CD62P浓度均显著增高( P值均<0.05);3个用药组与栓塞组相比,TF、CD62P的浓度均有不同程度的降低,其中治疗1周的联合用药组与栓塞组比降低最为明显。 结论:使用颈静脉注入异体血栓法可成功制备理想的肺栓塞大鼠模型;丹参川芎嗪与低分子肝素联合应用可显著降低肺栓塞大鼠CD62P及TF的水平。     

Failure of P-selectin blockade alone to protect the liver from ischemia-reperfusion injury in the isolated blood-perfused rat liver

AIM： To determine if blockade of P-selectin in the isolated blood-perfused cold ex vivo rat liver model protects the liver from ischemia-reperfusion injury. METHODS： The effect of P-selectin blockade was assessed by employing an isolated blood-perfused cold ex vivo rat liver with or without P-selectin antibody treatment before and after 6 h of cold storage in University of Wisconsin solution. RESULTS： In our isolated blood-perfused rat liver model, pre-treatment with P-selectin antibody failed to protect the liver from ischemia-reperfusion injury, as judged by the elevated aspartate aminotransferase activity. In addition, P-selectin antibody treatment did not significantly reduced hepatic polymorphonuclear leukocyte accumulation after 120 min of perfusion. Histological evaluation of liver sections obtained at 120 min of perfusion showed significant oncotic necrosis in liver sections of both ischemic control and P-selectin antibody-treated groups. However, total bile production after 120 rain of perfusion was significantly greater in P-selectin antibody-treated livers, compared to control livers. No significant difference in P-selectin and ICAM-1 mRNAs and proteins, GSH, GSSG, and nuclear NF-kB was found between control and P-selectin antibody-treated livers. CONCLUSION： In conclusion, we have shown that blockade of P-selectin alone failed to reduced polymorphonuclear leukocyte accumulation in the liver and protect hepatocytes from ischemia-reperfusion injury in the isolated blood-perfused cold-ex vivo rat liver model.     

TLR4对肝脏缺血再灌注损伤大鼠肝组织Th17细胞相关细胞因子表达的影响

目的 观察Toll样受体4（TLR4）对肝脏缺血再灌注大鼠肝组织Th17细胞相关因子[IL-17A、IL-23、孤核儿相关受体（RORrt）]表达的影响,并探讨其可能机制.方法 将40只健康雄性SD大鼠分为4组各10只,假手术组只分离同侧的颈总动脉和股动静脉,并进行相应插管注入相同剂量的肝素;模型组、抗TLR4组、同型抗体组均制备创伤失血性休克再灌注肝损伤模型,抗TLR4组、同型抗体组分别于再灌注前10 min经股静脉注入TLR4抗体50μg、同型对照抗体50 μg,整个过程用微量注射器缓慢注射.于12 h后处死取材.采用Western blot法检测各组肝组织TLR4蛋白,ELISA检测IL-17A、IL-23蛋白,观察IL-17A、IL-23、RORrt mRNA,并对模型组、抗TLR4组、同型抗体组IL-17A、IL-23、RORrt进行相关性分析.结果 模型组TLR4蛋白表达较假手术组相比明显升高（P＜0.01）,应用抗TLR4抗体后表达明显减少（P＜0.01）,而同型抗体组较模型组无明显差异（P＞0.05）.与假手术组比较,模型组、抗TLR4组、同型抗体组IL-17A、IL-23蛋白及mRNA表达升高,RORrt mRNA表达升高;与模型组比较,抗TLR4组IL-17A、IL-23蛋白及mRNA表达降低,RORrt mRNA表达降低（P＜0.05或0.01）.IL-23水平与IL-17A水平呈正相关,IL-23 mRNA水平与RORrt mRNA呈正相关.结论 中和TLR4可减少IL-23、IL-17A、RORrt的表达;机制可能是中和阻断TLR4可通过降低IL-23的表达,影响Th17特异性转录因子RORrt,进而降低肝脏缺血再灌注损伤大鼠肝组织Th17/IL-17A的表达.     

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。     

Ligustrazine alleviates acute lung injury in a rat model of acute necrotizing pancreatitis

Introduction Acute pancreatitis is often complicated by lung injury. However, its pathogenesis remains unclear. It is known that AP involves a complex array of mediators that can initiate and amplify the systemic inflammatory response. This can lead to the failure of distant organ systems, such as the lungs, heart and kidneys,[1-3] among which, pulmonary failure is the most common.[4-7] Recent studies have indicated that during the pathogenesis of acute necrotizing pancreatitis (ANP), chang…     

Anticoagulant pretreatment attenuates production of cytokine-induced neutrophil chemoattractant following ischemia-reperfusion of rat liver

We investigated whether anticoagulation would diminish ischemia-reperfusion injury of the liver. Liver ischemia was induced in rats by occluding the portal vein for 30 min. Anticoagulant was injected intravenously 10 min before occlusion. Serum concentrations of cytokine-induced neutrophil chemoattractant (CINC) in untreated rats increased following reperfusion, reaching a peak at 6 hr, then decreasing gradually to control levels by 24 hr. CINC levels in rats pretreated with heparin (50 units/kg), AT-III (250 units/kg), or DEGR-Xa (10 mg/kg) peaked at 3 hr after reperfusion and declined to baseline within 12 hr; peak CINC values were significantly lower than in untreated control rats. Expression of CINC mRNA in liver tissue paralleled the CINC serum levels. Both myeloperoxidase activity and the number of neutrophils in the liver were decreased in the anticoagulant groups. In addition, significant correlations were observed between the maximum values of AST, ALT, and LDH versus the peak CINC levels following ischemia-reperfusion. These results indicate that the release of CINC after ischemia-reperfusion of the liver is mediated by activation of coagulation within the hepatic microcirculation.