lncRNA PACER促进脓毒症急性肺损伤炎症反应的实验研究

目的探讨lncRNA PACER对小鼠脓毒症急性肺损伤炎症反应的促进作用。 方法分离和培养急性肺损伤和健康非吸烟者的肺泡巨噬细胞,以及获取细菌脂多糖(LPS)诱导的急性肺损伤(ALI)小鼠肺组织,采用qRT-PCR方法检测lncRNA PACER的表达;过表达或敲低PACER后,ELISA方法检测THP-1和RAW264.7细胞炎性因子肿瘤坏死因子-α(TNF-α)、白细胞介素-6(IL-6)的表达;对LPS所致ALI小鼠,尾静脉注射PACER siRNA慢病毒后,ELISA检测小鼠血清炎性因子TNF-α、IL-6的表达,HE染色观察肺组织病理学变化。 结果ALI患者肺泡巨噬细胞和ALI小鼠肺组织中lncRNA PACER表达均显著升高(P<0.01);细胞过表达PACER后,细胞炎性因子肿瘤坏死因子-α(TNF-α)、白细胞介素-6(IL-6)的表达升高,而敲低PACER后,炎性因子TNF-α、IL-6的表达则降低(P<0.01);ALI小鼠敲低PACER后,小鼠肺组织和血清中炎性因子TNF-α、IL-6的表达均显著降低(P<0.01),肺组织损伤程度明显减弱。 结论lncRNA PACER可显著促进脓毒症急性肺损伤炎症反应,为明确lncRNA PACER作为ALI防治的靶标提供了依据。     

厚朴酚对急性肺损伤大鼠肿瘤坏死因子-α、白细胞介素-1β的影响

目的观察厚朴酚对急性肺损伤(ALI)大鼠肿瘤坏死因子(TNF)-α、白细胞介素(IL)-1β的影响。方法选用健康雄性Wistar大鼠40只,随机分为对照组(10只)、ALI组(10只)、厚朴酚低剂量组(4μg/kg,10只)和厚朴酚高剂量组(8μg/kg,10只)。腹腔注射脂多糖(LPS)10 mg/kg 2 ml建立ALI大鼠模型;对照组给予等量生理盐水。治疗组于制模前30 min腹腔注射厚朴酚;每组于6、12、24 h 3个时间点取血,采用ELISA检测血清中TNF-α、IL-1β含量;于制模后24 h用水合氯醛腹腔注射麻醉并处死大鼠。取肺组织行HE染色并观察组织病理学改变。结果与对照组比较,ALI组TNF-α、IL-1β含量6、12、24 h明显升高(P<0.01);与ALI组比较,厚朴酚组TNF-α、IL-1β含量6、12、24 h即明显下降(P<0.01),两治疗组间炎症介质比较差异无统计学意义(P>0.05)。HE染色提示,厚朴酚干预组的肺组织病理改变明显好转。结论厚朴酚可下调大鼠血清中TNF-α、IL-1β含量,对脓毒症ALI大鼠的肺组织有抗炎作用。     

虾青素对脂多糖诱导小鼠急性肺损伤的保护作用

目的 研究虾青素对脂多糖(LPS)所致急性肺损伤(ALI)小鼠的保护作用.方法 雄性昆明种小鼠60只,随机分为正常对照组、急性肺损伤模型组、地塞米松阳性对照组(5 mg/kg)以及虾青素低、中、高剂量组(10、15、20 mg/kg)共6组.不同剂量虾青素给大鼠连续灌胃30 d后,腹腔注射脂多糖6.0 mg/kg建立ALI模型.在注射后6 h,收集腹主动脉血并进行左侧支气管肺泡原位灌洗以收集灌洗液,测定血中淋巴细胞亚群(CD+3、CD+4、CD+8)、肿瘤坏死因子α(TNF-α)、白细胞介素8(IL-8)及丙二醛(MDA)、超氧化物歧化酶(SOD)、谷胱甘肽过氧化物酶(GSH-Px)活性;测定各组的肺湿重/干重比、肺组织中性粒细胞髓过氧化物酶(MPO)含量及肺组织匀浆TNF-α、白细胞介素10(IL-10)含量.结果 虾青素各剂量组均能降低因LPS诱发的血TNF-α、IL-8、MPO、MDA含量与肺组织湿重/干重比的升高,同时抑制肺组织IL-10含量、血SOD与GSH-Px活性的降低,改善血中淋巴细胞亚群分布.结论 虾青素对LPS所致ALI具有预防性保护作用.     

ANGPTL4免疫脂质体对急性肺损伤小鼠的治疗作用

目的探讨ANGPTL4免疫脂质体对转染脂多糖(lipopolysaccharide,LPS)诱发的急性肺损伤(acute lung injury,ALI)小鼠,肺损伤的影响。方法采用逆相蒸发法制备ANGPTL4基因表达质粒与抗CD31抗体偶联的免疫脂质体;LPS诱发急性肺损伤小鼠模型;观察经ANGPTL4免疫脂质体转染的急性肺损伤小鼠的肺部炎症因子肿瘤坏死因子-α(tumor necrosis factor-α,TNF-α)、白细胞介素-6(interleukin-6,IL-6)水平和中性粒细胞活化标志物髓过氧化物酶(myeloperoxidase,MPO)表达的变化,以及小鼠肺组织病理变化和肺血管通透性的改化。结果 ANGPTL4免疫脂质体可以有效增加小鼠肺内ANGPTL4的表达;进而降低ALI小鼠肺泡灌洗液中的TNF-α、IL-6水平和MPO的表达;降低ALI小鼠肺组织湿干比和肺泡灌洗液蛋白浓度,减轻肺组织病变程度。结论 ANGPTL4免疫脂质体能有效减轻LPS诱导的ALI小鼠的肺部炎症损伤反应。     

TNF-α中和对脂多糖致急性肺损伤小鼠肺组织凋亡的影响

目的 评价TNFR-Fc通过下调炎症反应、抑制组织细胞凋亡,对脂多糖(LPS)致急性肺损伤(ALI)小鼠肺组织的保护性作用.方法小鼠随机分为LPS组、TNFR-Fc+ LPS组和对照组.气管内滴人LPS复制ALI小鼠模型,TNFR-Fc+ LPS组在滴人LPS前24 h腹膜腔注射TNFR-Fc 0.4mg/kg体质量,在滴入LPS后2h收集标本.ELISA法检测血清肿瘤坏死因子α(TNF-α)及支气管肺泡灌洗液(BALF)中TNF-α、白介素1β(IL-1β)与IL-6浓度,BCA法检测BALF中蛋白含量,qRT-PCR法检测Bax基因转录强度,末端脱氧核苷酸转移酶介导的dUTP原位切口末端标记法检测肺组织细胞凋亡率,组织病理半定量评分评价肺组织损伤程度.结果 LPS气管内滴入后,BALF中TNF-α、IL-6浓度与肺泡蛋白含量显著升高(P＜0.05),肺组织Bax基因转录强度均显著增高(P＜0.05),给予TNFR-Fc预处理显著降低血清TNF-α浓度,BALF中IL-6浓度与蛋白含量也显著下降(P＜0.05),下调Bax基因的转录强度(P＜0.05).与LPS组相比,TNFR-Fc+ LPS组小鼠肺组织细胞凋亡率、病理评分均显著降低(P＜0.05).结论 中和TNF-α能下调肺局部炎症反应强度,减少LPS致ALI小鼠肺组织细胞凋亡,降低LPS气管内滴人引起的肺组织损伤程度.     

硫化氢对脂多糖所致急性肺损伤大鼠血浆和肺组织中炎性细胞因子的影响

目的初步探讨硫化氢(H2S)对脂多糖(LPS)所致SD大鼠急性肺损伤(ALI)的保护作用。方法将112只SD大鼠随机分为四组:盐水对照组、内毒素(LPS)组、LPS+(NaHS)组、LPS+炔丙基甘氨酸(PPG)组,每组28只,分别取7只于给药2、4、6、8 h后,应用细胞因子酶联免疫蛋白吸附法(ELISA)法检测各时间点血浆及肺组织中TNF-α、IL-6和IL-4含量,并观察其峰值形成时间变化趋势。结果盐水对照组大鼠的血浆及肺组织中,TNF-α、IL-4浓度均低于检测的下限,IL-6在血浆及肺组织中浓度分别为:(44.03±3.57)ng/L和(48.14±5.68)ng/L;与盐水对照组相比,滴注LPS后大鼠血浆及肺组织中TNF-α、IL-6、IL-4的浓度水平均出现升高,且TNF-α表达峰值的时间也早于IL-6,IL-4的高峰在6 h,要晚于TNF-α、IL-6,但持续时间较长;与LPS组相比,PPG+LPS组大鼠TNF-α、IL-6浓度水平升高,IL-4水平高峰后移至8 h;但NaHS+LPS组大鼠血浆和肺组织中TNF-α、IL-6浓度水平则显著下降,IL-4的水平高峰可前移至4 h(P均<0.01)。结论 H2S能够抑制促炎因子TNF-α、IL-6的增加,并促进抗炎因子IL-4的表达且使其释放高峰提前来减轻机体过度的炎症反应,从而对抗LPS所致急性肺损伤ALI。     

三七总皂苷对急性肺损伤大鼠血清和支气管肺泡灌洗液肿瘤坏死因子α、白介素6和白介素10水平的影响

目的观察三七总皂苷(PNS)对油酸-脂多糖(OA-LPS)序贯致急性肺损伤(ALI)大鼠血清和支气管肺泡灌洗液(BALF)中肿瘤坏死因子α(TNF-α)、白介素6(IL-6)和白介素10(IL-10)水平的影响。方法 28只SD大鼠随机分为4组,每组7只。A组为0.9%氯化钠溶液(NS)对照组,B组为ALI模型对照组,C组为ALI模型+PNS治疗组,D组为ALI模型+PNS+机械通气治疗组,D组实验动物予以气管插管建立人工气道并实施机械通气支持〔潮气量(VT)15ml/kg,呼气末正压(PEEP)0 cmH2O,吸入氧浓度(FiO2)21%〕。应用油酸尾静脉注射-脂多糖间隔4h腹腔注射建立ALI大鼠模型。成模后C、D两组给予PNS(100mg/kg尾静脉注射)。连续监测各组大鼠的通气参数及动脉血气分析变化。成模后4h处死动物,收集血清和BALF。采用酶联免疫法(ELISA)检测TNF-α、IL-6和IL-10含量。结果 4组大鼠动脉血二氧化碳分压(PaCO2)比较,差异无统计学意义(P>0.05)。4组动脉血氧分压/吸入氧浓度(PaO2/FiO2)、湿/干重比(W/D)比较,差异均有统计学意义(P<0.05)。C、D组大鼠PaO2/FiO2与B组比较,差异有统计学意义(P<0.01);PNS注射后C、D两组大鼠的W/D值与B组比较,差异有统计学意义(P<0.01)。PNS注射后C、D两组大鼠的血清和BALF中的TNF-α、IL-6和IL-10水平均显著降低,差异有统计学意义(P<0.01);PNS联合机械通气的D组较单独运用PNS的C组大鼠TNF-α、IL-6和IL-10水平无明显变化,差异无统计学意义(P>0.05)。结论 TNF-α和IL-6是ALI发生发展过程中重要的促炎症细胞因子,TNF-α和IL-6水平增高与肺损伤严重程度密切相关。IL-10则能抑制炎症反应。PNS对OA-LPS致ALI大鼠具有一定的保护作用,减轻肺水肿,减少炎症细胞因子的生成释放,缓解低氧血症。     

瑞舒伐他汀钙对老年脓毒症模型大鼠急性肺损伤的干预作用

目的探讨瑞舒伐他汀钙对老年脓毒症大鼠急性肺损伤的干预作用。方法将72只老年雄性Wistar大鼠随机分为假手术组、模型组、瑞舒伐他汀钙干预组,每组24只。干预组及模型组采用改良盲肠结扎穿孔术方法建立老年脓毒症ALI大鼠模型,假手术组建立假手术模型。术前1 w干预组开始每日给予瑞舒伐他汀钙,剂量2.5 mg·kg~(-1)·d~(-1)。模型组和假手术组同一时间给予等量生理盐水。实验前24 h灌注药物后禁食,自由饮水。每组大鼠平均分为3个亚组,分别于术后6、12和24 h取材。应用酶联免疫吸附法(ELISA)检测血清细胞因子白细胞介素(IL)-2、IL-6、肿瘤坏死因子(TNF)-α水平、检测动脉血氧分压(PaO_2)并观察肺组织的病理改变。结果模型组PaO_2明显低于假手术组和干预组(P<0.05),且随时间延长而降低。模型组血清细胞因子IL-2、IL-6、TNF-α水平高于假手术组和干预组(P<0.05),与模型组比,干预组肺损伤程度较轻。结论瑞舒伐他汀钙能抑制老年脓毒症大鼠ALI的炎症反应、改善氧分压,进而减轻ALI。     

脂多糖致肺血管内巨噬细胞释放TNFα-、IL-1β及IL-8的改变

目的探讨肺血管内巨噬细胞（PIM）在感染性急性肺损伤（ALI）发病中的作用。方法仿Morton法灌洗肺血管床,贴壁法分离猪PIM,培养于RPM I 1640培养基,予10 mg/L脂多糖（LPS）刺激,胸腺细胞增殖法测PIM培养上清白细胞介素-1β（IL-1β）活性,酶联免疫吸附试验（ELISA）法测肿瘤坏死因子-α（TNF-α）和白细胞介素-8（IL-8）含量。结果 LPS刺激后,PIM释放TNF-α、IL-1β和IL-8增多,峰值分别出现在刺激后的1、2和6 h。与刺激前相比,P〈0.01。结论 LPS刺激后,PIM分泌多种细胞因子,其中TNFα-、IL-1β升高最早,提示其在ALI发病早期起重要作用;而IL-8升高较晚,且后者持续时间较长,可能对ALI的病情进展起重要作用。细胞因子间的相互作用在ALI的发病中似乎更为重要。     

黄连素对波动性高糖导致的人冠状动脉内皮细胞炎症反应的影响

目的:研究黄连素(BBR)对波动性高糖导致的人冠状动脉内皮细胞(HCAECs)炎症反应的作用。方法:分离、培养HCAECs,将HCAECs分为5组。正常血糖组(NG组)加入5.5 mmol/L葡萄糖;持续性高糖组(PHG组)加入25 mmol/L葡萄糖;波动性高糖组(IHG组)加入5.5 mmol/L葡萄糖和25 mmol/L葡萄糖24 h波动1次;对照组(OC组)加入5.5 mmol/L和25 mmol/L甘露醇24 h波动1次,为波动性高渗环境;波动性高糖+黄连素组(IHG+BBR组):5.5 mmol/L葡萄糖和25 mmol/L葡萄糖+50μmol/L黄连素24 h波动1次。以上5组HCAECs培养7 d。用酶联免疫吸附实验(ELISA)测定白细胞介素-1β(IL-1β)、肿瘤坏死因子-α(TNF-α)、人单核细胞趋化蛋白-1(MCP-1)和白细胞介素-10(IL-10)等炎症指标的蛋白水平,实时荧光定量聚合酶链式反应(qRT-PCR)测定IL-1β、TNF-α、MCP-1和IL-10的mRNA表达。结果:PHG组和IHG组IL-1β、TNF-α、MCP-1水平较NG组和OC组...     

Pulmonary injury from transfusion-related acute lung injury

Transfusion-related acute lung injury (TRALI) can be a life-threatening complication of transfusion. In its severe form, it is clinically indistinguishable from acute respiratory distress syndrome. Symptoms typically begin within 4 hours of transfusion. TRALI has been reported after transfusion of all plasma-containing blood components. TRALI is associated with antibodies to white blood cells and biologically active lipids in trans-fused blood components.     

Reperfusion injury

This article reviews the early and late morphologic changes associated with reperfusion of ischemic myocardium. If instituted within minutes of coronary artery occlusion, all reversibly injured myocardium is salvaged. Once some irreversibly injured myocardium is present, the usually bland region of coagulation necrosis is transformed into an edematous, hemorrhagic zone with "contraction-band" necrosis and vascular obstruction (no-reflow phenomenon). Whether or not these changes occur in otherwise salvageable myocardium is controversial. Data from studies with conflicting results are presented. Popular proposed mechanisms of reperfusion injury include the no-reflow phenomenon and free radical-mediated injury. No reflow has been related to direct vascular injury, compression of capillaries by edema fluid, and obstruction of vascular channels by leukocytes. Free radicals, which inactivate enzymes and destroy membranes, are primarily oxygen derived, and produced by neutrophils, endothelial cells, and myocardial cells. Whether or not reperfusion injury exists is still debated; if it does, the mechanism of injury remains to be proven. Ongoing research in this field will augment our knowledge of cell death and interventions to delay or prevent it.     

Ballistic injury

Wound profiles made under controlled conditions in the wound ballistics laboratory at the Letterman Army Institute of Research showed the location along their tissue path at which projectiles cause tissue disruption and the type of disruption (crush from direct contact with the projectile or stretch from temporary cavitation). Comparison of wound profiles showed the fallacy in attempting to judge wound severity using velocity alone, and laid to rest the common belief that in treating a wound caused by a high-velocity missile, one needs to excise tissue far in excess of that which appears damaged. All penetrating projectile wounds, whether civilian or military, therefore should be treated the same regardless of projectile velocity. Diagnosis of the approximate amount and location of tissue disruption is made by physical examination and appropriate radiographic studies. These wounds are contaminated, and coverage with a penicillin-type antibiotic should be provided.     

Spinal-cord injury

More than a decade ago, spinal-cord injury meant confinement to a wheelchair and a lifetime of medical comorbidity. The physician's armamentarium of treatments was very limited, and provision of care for individuals with spinal-cord injury was usually met with frustration. Advances in the neurosciences have drawn attention to research into spinal-cord injury. Nowadays, advanced interventions provide high hope for regeneration and functional restoration. As scientific advances become more frequent, scepticism is giving way to the ideas that spinal-cord injury will eventually be repairable and that strategies to restore function are within our grasp. We address the present understanding of spinal-cord injury, its cause, pathophysiology, diagnosis, and treatment, and look at promising research avenues. We also discuss new treatment options, including functional electric stimulation and part-weight-supported walking.     

Near-hanging injury

Near-hanging injury results in multisystem insult and injury. Acute or delayed respiratory complications can result in death. A survivor can suffer neuropsychiatric sequelae ranging from amnesia to a prolonged vegetative state. Treatment is directed toward ensuring cerebral oxygenation, lowering increased intracranial pressure, and treating respiratory distress. Psychiatric consultation will be necessary in long-term survivors. Patients should be observed for at least 24 hours after a near-hanging injury.     

衰老大鼠急性肺损伤诱导肝功能受损的研究

目的　观察脂多糖 (LPS)致衰老大鼠的急性肺损伤 (ALI)是否可进一步诱发肝功能受损及银杏叶提取物 (GBE)对其是否有保护作用。方法　雄性Wistar大鼠 3 0只复制成衰老模型。再随机分成对照组 (静脉注射生理盐水 ) ;LPS组 (静脉注射LPS)及GBE +LPS组 (注LPS前 7天开始每天GBE灌胃 1次 )。注LPS后 2、6h收集血液并取肺、肝。制备肺、肝组织匀浆待测。结果　衰老大鼠在注射LPS后 2、6h时形成ALI。对照组注射LPS表明 ,2h血中总胆红素含量及谷丙转氨酶 (GPT)活性为(10 9± 0 6)mg/L、(2 6± 3 )U ,LPS 6h组为 (3 0 1± 2 1)mg/L、(88± 12 )U ,两组比较差异有显著性 (P均<0 0 0 1) ;对照组注射LPS表明 ,2h血和肺组织中每毫克蛋白中丙二醛 (MDA)含量分别为 (15 9±1 8) μmol/L、(18 8± 2 1)nmol,LPS 2h组为 (2 2 1± 1 9) μmol/L、(2 8 8± 3 1)nmol,两组比较差异有显著性 (P均 <0 0 0 1) ;而每毫克蛋白血和肺组织中超氧化物歧化酶 (SOD)活性对照组分别为 (2 5 5±2 6)mU/L、(3 6 1± 2 4)U ,LPS 2h组分别为 (2 0 6± 1 9)mU/L、(3 2 0± 2 7)U ,两组比较差异有显著性(P <0 0 1和 0 0 5 )。对照组注射LPS表明 ,2h时肺组织中每毫克蛋白中谷胱甘肽过氧化物酶 (GSH PX)及Na+ K+ ATP酶活性     

Repetitive strain injury

Repetitive strain injury remains a controversial topic. The term repetitive strain injury includes specific disorders such as carpal tunnel syndrome, cubital tunnel syndrome, Guyon canal syndrome, lateral epicondylitis, and tendonitis of the wrist or hand. The diagnosis is usually made on the basis of history and clinical examination. Large high-quality studies using newer imaging techniques, such as MRI and ultrasonography are few. Consequently, the role of such imaging in diagnosis of upper limb disorders remains unclear. In many cases, no specific diagnosis can be established and complaints are labelled as non-specific. Little is known about the effectiveness of treatment options for upper limb disorders. Strong evidence for any intervention is scarce and the effect, if any, is mainly short-term pain relief. Exercise is beneficial for non-specific upper limb disorders. Immobilising hand braces and open carpal tunnel surgery release are beneficial for carpal tunnel syndrome, and topical and oral non-steroidal anti-inflammatory drugs, and corticosteroid injections are helpful for lateral epicondylitis. Exercise is probably beneficial for neck pain, as are corticosteroid injections and exercise for shoulder pain. Although upper limb disorders occur frequently in the working population, most trials have not exclusively included a working population or assessed effects on work-related outcomes. Further high-quality trials should aim to include sufficient sample sizes, working populations, and work-related outcomes.