姜黄素和地塞米松对大鼠移植肺缺血再灌注损伤的保护作用

目的：研究姜黄素（CUR）和地塞米松（DXM）对大鼠移植肺缺血再灌注损伤的干预作用。方法：实验分四组进行，CUR组肺移植前3h供、受者腹腔注射CUR溶液；DXM组肺移植前30min受者腹腔注射DXM溶液；载体组肺移植前3h供、受者腹腔注射CUR的溶剂二甲基亚砜；假手术组不进行肺移植。每组分别于恢复血液再灌注2h和24h各处死大鼠6只，采取颈动脉（CA）血和左肺静脉（LPV，移植侧）血，测定血氧合指数（PO2／FiO2）以及血清中丙二醛（MDA）、总抗氧化能力（TAOC）、肿瘤坏死因子（TNF-α）、白细胞介素6（IL-6）的含量；同时行肺组织病理学观察，测定肺湿重与干重比（W／D），以及肺组织中髓过氧化物酶活性（MPO）、MDA、TAOC、TNF-α、IL-6的含量。结果：再灌注2h及24h，CUR组及DXM组LPV血的PO2／FiO2明显高于载体组（P〈0．01）。CUR组与DXM组再灌注2h和24h的肺水肿病理评分和总分明显低于载体组（P〈0．017），CUR组与DXM组再灌注24h的W／D明显低于载体组（P〈0．01）。再灌注2h和24h，CUR组与DXM组肺组织中MPO含量明显低于载体组（P〈0．05，P〈0．01）。再灌注2h时，CUR组和DXM组血清和组织中MDA含量明显低于载体组（P〈0．05），再灌注24h时，CUR组血清MDA含量和DXM组组织中MDA含量明显低于载体组（P〈0．05）。再灌注2h和24h，CUR组肺组织和血清中TAOC含量明显高于载体组（P〈0．01，P〈0．05），而DXM组仅再灌注2h的肺组织和再灌注24h的血清中TAOC含量高于载体组（P〈0．01）。再灌注2h和24h，CUR组和DXM组肺组织中TNF-α和IL-6含量低于载体组。结论：CUR和DXM对大鼠移植肺缺血再灌注损伤具有保护作用，其机制可能与二者具有抗氧化和抗炎作用有关。     

一氧化氮减轻大鼠移植肺缺血/再灌注损伤的作用及机制

目的探讨供、受者在肺移植前后吸入低浓度一氧化氮（NO）对移植肺缺血／再灌注损伤的影响及其机制。方法取6（）只雄性SD大鼠，随机配对建立左肺移植模型。实验分为2组，NO组：获取供肺前，供者在移植肺灌洗期吸人体积分数为0．001％的NO；肺移植后，受者在移植肺再灌注后10min-2h持续吸入相同浓度的NO。对照组：供、受者肺移植前后不做任何特殊处理，只进行肺移植。供者开胸时及受者再灌注2h后，分别夹闭右肺门5min，进行动脉血气分析检测。受者术前及再灌注后2h时分别检测肺功能和动脉血气分析。再灌注2h后，取移植肺组织测髓过氧化物酶（MPO）活性、丙二醛（MDA）含量、肺湿／干重比（W／D）以及诱生型一氧化氮合酶（iNOS）的活性及其mRNA表达，并观察移植肺的病理学形态。结果移植肺再灌注2h后，NO组动脉血氧分压／吸氧浓度（PaO2／FiO2）值较对照组升高，氧合指数（OI）值、肺内分流（Qs／Qt）值较对照组降低，两组相比，差异有统计学意义（P均〈0．05）。NO组与对照组相比，MPO活性明显降低，MDA含量明显增高，W／D无显著差异。NO组iNOS蛋白活性及其mRNA表达均较对照组显著降低，iNOS主要表达在肺泡上皮细胞、肺泡腔和间质内浸润的炎症细胞。NO组炎症细胞浸润明显较对照组轻。结论供、受者在肺移植前后吸入低浓度NO能改善移植肺的氧合、减轻缺血／再灌注损伤，其机制可能与NO减少肺内分流、下调iNOS表达以及减轻肺内炎症细胞浸润有关。     

N-脱硫酸肝素对大鼠移植肺缺血再灌注损伤的影响

目的评价N-脱硫酸肝素（NNH）对大鼠移植肺缺血再灌注损伤的影响。方法纯种雄性sD大鼠20只，体重280～350g，随机分为2组（n=10），对照组（C组）再灌注即刻静脉注射生理盐水1．2ml／kg；NNH组再灌注即刻静脉注射NNH12mg／kg。在呼吸机支持和显微镜辅助下，利用非内皮化袖套式方法，建立大鼠左肺移植模型。再灌注2h后取肺静脉血进行血气分析，取移植肺组织，计算肺湿，干重比（W／D），测定髓过氧化物酶（MPO）、肿瘤坏死因子-α（TNF-α）和白细胞介素-8（IL-8）、细胞间黏附分子-1（ICAM-1）mRNA的水平，光镜下观察肺组织的病理学变化。结果与C组比较，NNH组肺静脉血氧分压升高，肺W／D、TNF-α、IL-8和ICAM-1 mRNA水平降低（P〈0．05或0．01），肺静脉血二氧分碳分压和MPO活性差异无统计学意义（P〉0．05）。光镜下NNH组肺组织中性粒细胞浸润和水肿程度均比C组轻。结论静脉注射NNH12mg/kg可减轻大鼠移植肺缺血再灌注损伤，与降低肺组织炎性反应有关。     

L-N6-(1-亚氨乙基)赖氨酸对大鼠移植肺缺血再灌注损伤的影响

目的 探讨L-N6-(1-亚氨乙基)赖氨酸(L-NIL)对大鼠移植肺缺血再灌注损伤的影响.方法 清洁级雄性SD大鼠18只,体重250～350 g,随机分为3组(n=6),假手术组(S组);肺移植组(L组)肺移植后恢复再灌注,冷缺血时间约1 h;L-NIL组再灌注即刻经尾静脉输注L-NIL 3 mg/kg.各组均于再灌注即刻经尾静脉注射0.5%伊文氏蓝0.2 ml.再灌注2 h时取左肺组织,测定肺湿/干重(W/D)比、伊文氏蓝含量、MDA含量、髓过氧化物酶(MPO)、诱导型一氧化氮合酶(iNOS)及内皮源性一氧化氮合酶(eNOS)活性;并行病理学观察.结果 与S组比较,L组肺组织W/D比和伊文氏蓝含量增加,MDA含量、MPO及iNOS活性升高,eNOS活性降低(P＜0.05).与L组比较,L-NIL组肺组织W/D比和伊文氏蓝含量减少,MDA含量、MPO及iNOS活性降低,eNOS活性升高(P＜0.05),肺组织毛细血管内充血减少,炎性细胞浸润减少.结论 再灌注早期静脉注射L-NIL可减轻大鼠移植肺缺血再灌注损伤.     

大鼠离体肺缺血再灌注时肺组织中水通道蛋白的表达及意义

肺移植中的缺血再灌注损伤所致的肺水肿是导致受者早期死亡的常见原因[1],临床治疗肺移植后的肺水肿,疗效欠佳.以往的研究多认为肺水肿与炎症介质和细胞因子的过度释放有关[2],而对水通道蛋白(AQP)在肺损伤中的作用研究甚少.本实验利用大鼠建立离体肺缺血再灌注模型,从离子通道水平认识缺血再灌注损伤对肺组织中AQP表达的影响,报告如下.     

舒芬太尼后处理对子宫缺血-再灌注大鼠急性肺损伤的影响

目的研究舒芬太尼后处理对子宫缺血-再灌注(IR)大鼠急性肺损伤的影响。方法成年雌性SD大鼠45只,随机分为三组:对照组(C组)、IR组和舒芬太尼后处理组(SPC组),每组15只。IR组、SPC组建立子宫缺血45 min再灌注2 h模型,SPC组给予舒芬太尼后处理。检测大鼠处理后子宫、血清及肺组织中TNF-α、丙二醛(MDA)含量、超氧化物歧化酶(SOD)活性以及肺湿干重比(W/D)、肺通透性指数(LPI)。结果 IR组、SPC组子宫、血浆及肺脏中TNF-α、MDA含量、W/D、LPI明显高于C组(P0.05);SPC组TNF-α、MDA含量、W/D、LPI明显低于IR组(P0.05);IR组、SPC组子宫、血浆以及肺脏中SOD活性明显低于C组(P0.05);SPC组SOD活性明显高于IR组(P0.05)。结论舒芬太尼后处理能减轻子宫缺血-再灌注大鼠急性肺损伤,可能与减少氧自由基和炎症因子的产生,降低肺通透性,减轻肺水肿,从而减轻子宫缺血-再灌注大鼠引发的急性肺损伤有关。     

内皮祖细胞减少肺移植后的缺血-再灌注损伤

目的观察内皮祖细胞对肺缺血-再灌注损伤的影响。方法 24只受体鼠随机分为:假手术(S)组,磷酸盐缓冲液(phosphate-buffered saline,PBS)组和内皮祖细胞(endothelial progenitor cell,EPC)组。假手术组仅接受麻醉,PBS组肺移植再灌注后立即注射PBS,EPC组再灌注后立即注射EPC。再灌注24 h后测量氧合指数,血清炎症因子浓度,测量移植肺湿干重比和蛋白质浓度及核转录因子(NF)-κB的表达,观察移植肺组织学损伤情况。结果与PBS组比较,EPC增加再灌注后氧合指数,降低移植肺湿干重比和蛋白浓度,减少血清促炎因子的生成、促进抗炎因子的释放。EPC降低移植肺组织中NF-κB的表达,减轻肺移植后组织学损伤。结论 EPC可以减轻肺移植缺血-再灌注损伤,其作用与改善肺移植后肺泡-毛细血管通透性,抑制移植肺和全身炎症反应有关。     

缺血预处理的模拟方法对供肺的保护效果

目的 探讨使用外源性药物模拟缺血预处理对供肺的保护效果。方法 使用腺苷模拟缺血预处理的早期保护作用；使用超氧化物歧化酶(SOD)模拟延迟保护作用；两者合用模拟全过程；并设对照组。将各组家兔的供肺灌注、取出、加或不加药物，保存6h后，用离体兔肺再灌注模型进行再灌注1h，测动脉血氧分压(PaO2)、气道压、肺顺应性、湿／干重比值、一氧化氮合酶(NOS)含量，并作光镜、电镜切片检查。结果各组PaO2值从低到高为空白对照组、SOD组、腺苷组、腺苷及SOD合用组，各组间差异均有显著性。各组湿／干重比值从高到低为空白对照组、腺苷组、SOD组、腺苷及SOD合用组，各组间差异均有显著性。模拟缺血预处理组的气道压、NOS含量低于空白对照组，肺顺应性高于空白对照组，但各组间差异无显著性。光镜、电镜显示模拟缺血预处理组的病变比对照组明显减轻。结论使用外源性药物模拟缺血预处理可以提高供肺的氧合功能，减轻肺水肿；虽然对改善气道压、肺顺应性和NOS活性作用不大，但仍能说明模拟缺血预处理对供肺有保护作用。     

丝裂原活化蛋白激酶在一氧化碳抗大鼠肢体缺血再灌注所致肺损伤中的作用

目的 观察丝裂原活化蛋白激酶(MAPKs)在外源性一氧化碳(C0)抗大鼠肢体缺血再灌注(IR)所致肺损伤中的作用。方法 健康SD大鼠，随机分为4组(每组n=8)：对照组(Con-trol)、Control CO、IR和IR CO组。复制大鼠双后肢缺血及再灌注后肺损伤模型。IR CO和Control CO组在再灌注前1h或相应时间点置含CO的空气中，其余两组呼吸空气。观察大鼠肺组织学、肺组织中中性粒细胞(PMN)数目、肺组织湿重和干重之比(W／D)、丙二醛(MDA)含量以及动物生存情况变化。应用Western blotting检测肺组织中三种磷化MAPKs，即细胞外信号调节激酶(ERK)、c-Jun氨基末端激酶(JNK)和p38表达的变化。结果 与Contorl组相比。IR组动物死亡率、肺组织PMN数目、W／D、MDA含量以及磷酸化ERK、JNK和p38表达均显著增高；与IR组相比，IR CO组IR组动物死亡率、肺组织中PMN数目、W／D和MDA含量均显著降低、肺损伤减轻，p38表达显著增高，JNK表达显著降低，ERK表达无显著变化。结论 MAPKs信号通路参与了外源性CO抗大鼠肢体IR所致肺损伤作用的分子机制。     

血液稀释对兔肺缺血再灌注损伤的影响

目的 观察肺缺血前、后血液稀释对肺缺血再灌注(I／R)损伤的影响，探讨血液稀释对肺缺血再灌注损伤的干预作用及机制。方法 采用兔单肺原位缺血再灌注损伤模型，术中不同时点进行急性等容血液稀释。实验分四组：对照组(单纯开胸，C)，缺血-再灌注组(I／R)，缺血-稀释-再灌注组(IHR)，稀释-缺血-再灌注组(HIR)。血液稀释时采用颈动脉放血，同时静脉补入等量低分子右旋糖酐。分别于肺缺血前、缺血1h、再灌注1h采血检测超氧化物歧化酶(SOD)、一氧化氮(NO)，记录呼吸道峰压(Ppeak)。术毕测定血内丙二醛(MDA)、肺组织湿，干比值(W／D)及病理改变。结果 C组、IHR组和HIR组的W，D、MDA、P peak和肺组织炎性改变及肺水肿指标在术毕或缺血1h明显低于I／R组；而SOD却明显高于I／R组；HIR组Ppeak、术毕W，D、MDA低于IHR组，组织病理检查显示水肿及白细胞浸润程度比IHR组轻。结论 血液稀释对肺I／R损伤有预防、治疗作用；缺血前稀释血液效果更明显。适度的血液稀释对肺缺血再灌注损伤具有预防和治疗作用。     

Horseshoe lung with left lung hypoplasia.

Horseshoe lung is an uncommon congenital malformation in which the bases of the right and the left lungs are fused to each other by a narrow isthmus posterior to the cardiac apex. So far 22 cases have been described: most of these were associated with right lung hypoplasia and the scimitar syndrome. A horseshoe lung anomaly with left lung hypoplasia is described.     

Technetium-fibrinogen lung scanning in canine lung contusion

To detect experimentally induced acute lung contusion in anesthetized dogs, serial radionuclide images of the lung were recorded following intravenous infusion of 99mTc-labelled human fibrinogen (Tc-HF). The accumulation of Tc-HF in canine lungs was serially quantitated for up to 20 hours after lung contusion. A contusion (#1) was produced in one lung, Tc-HF was injected IV after 15 minutes, and 75 minutes later a contralateral lung contusion (#2) was produced in a series of 14 dogs. At autopsy the excised lungs were scanned, sectioned, and counted for radioactivity. Radiolabelled fibrinogen accumulated within 2-4 minutes of contusion #2 and remained stable over the next 20 hours in 14 dogs; contusion #1 was barely visible in four dogs. Lung Tc-HF activity in the central region of contusion #2 remained sixfold higher than in normal lung tissue. These data suggest that following lung contusion, fibrinogen deposition occurs rapidly and remains stable over a 20-hour interval of observation.     

Septic lung and shock lung in man.

Two series of patients were studied by serial measurements of blood gas exchange and pulmonarmonary dysfunction and to evaluate the dangers of respiratory failure in post traumatic patients. There were 27 patients who had sustained profound hemorrhagic shock and massive blood replacement averaging 9.7 liters and 38 patients who suffered general peritonitis or other forms of fulminating nonthoracic sepsis. All were supported by endotrachael intubation and volume controlled ventilators. The overall mortality for the post shock patients without sepsis was 12% while in the septic patients it was 35%. The maximal pulmonary arteriovenous shunt encountered in the post hemorrhagic shock patients at 36 hours averaged 20 plus or minus 8% and was accompanied by high cardiac indices (average 5.1 plus or minus 1.3 L/M-2/min) but no significant rise of pulmonary arterial pressure or peak inspiratory pressure (PIP). Severe pulmonary dysfunction subsequently occurred only in those patients who later became septic. The studies on the septic patients were divided according to the magnitude of the cardiac indices (the high indices averaged 4.8 plus or minus 1.6L/M-2/min) and thelow indices averaged 1.9 plus or minus 1.0 L/M-2/min. In the former, the average maximal shunt of 30 plus or minus 6% was sustained for 4 or more days, accompanied by an elevation of PIP to 36 plus or minus 6 cm H2O and by Pa pressure of 28 plus or minus 5 mm Hg. The patients in low output septic shock usually had an associated bronchopneumonia and had an average venous admixture of 34 plus or minus 8% and PIP values of 41 plus or minus 8 cm H2O. The mean Pa pressure in this group was 29 plus or minus 6 mm Hg.     

Living-donor lobar lung transplantation for infectious lung diseases

The rate of infection among lung transplant recipients is several times higher than that among recipients of other organs and is most likely related to the exposure of the allograft to the external environment. Meticulous peri-operative management is mandatory in performing living-donor lobar lung transplantation for patients with infectious lung diseases. All 5 patients with end-stage infectious lung diseases are currently alive for 17-104 months after receiving living-donor lobar lung transplantation at Okayama University Hospital.     

Videothoracoscopy-assisted surgical lung biopsy for interstitial lung diseases

Objectives

Surgical lung biopsy (SLB) by videothoracoscopy for diffuse interstitial lung diseases is recommended for detailed diagnosis. Because substantial mortality and morbidity are associated with this procedure, its safety and diagnostic yield should be validated.

Methods

Sixty-four patients with diffuse interstitial lung disease who received SLB by videothoracoscopy between 2007 and 2013 were retrospectively analyzed for mortality, surgical complication, and diagnosis. Criteria for the procedure included patients <70-year old, who had at least 60 % vital capacity and at least 40 % diffusion capacity. Patients with radiologically definite usual interstitial pneumonia were not eligible.

Results

One conversion from the 3-port approach to thoracotomy due to bleeding occurred. Mean operation and anesthesia times were 63 and 133 min, respectively. The mean hospital stay was 6 days. Only 10 patients (16 %) received prophylactic steroid and/or elastase inhibitor administration. Neither deaths nor acute exacerbations of interstitial pneumonia occurred within 60 days after surgery. Pneumothorax occurred in four cases (6 %) after discharge, which was associated with lower % vital capacity and intraoperative steroid administration. Prolonged air leak and postoperative pneumonia were observed in 2 and 1 patients, respectively. Postoperative diagnosis was obtained in all patients. A group of connective tissue disease-related interstitial pneumonia (n = 15) and chronic hypersensitivity pneumonitis (n = 18) were the major diagnoses. Discordance between pre- and postoperative diagnoses was observed among usual interstitial pneumonia, non-specific interstitial pneumonia, and chronic hypersensitivity pneumonia.

Conclusions

Surgical lung biopsy for diffuse interstitial lung diseases is safe under appropriate inclusion criteria and provides definite diagnosis.