七氟醚对肺缺血-再灌注损伤兔的保护作用

目的探讨七氟醚对兔肺缺血 再灌注损伤的保护作用及可能机制。方法96只日本大耳白兔，随机分为4组（n=24）：假手术组（S组）、缺血再灌注组（IR组）、七氟醚缺血 再灌注组（Sev IR组）和七氟醚组（Sev S）。IR组、Sev IR组参照Eppinger方法建立肺缺血再灌注模型，Sev IR 组 吸入肺泡最小有效浓度（MAC）七氟醚30 min后行缺血 再灌注，Sev S组吸入1MAC七氟醚30 min后不进行缺血再灌注。分别在缺血45 min、再灌注60，120 min处死兔，行动脉血气分析，测定肺组织湿干重比（W/D）、TNFα、IL 1β和IL 10的含量以及MPO的活性、支气管肺泡灌洗液（BALF）中白细胞分类计数、肺通透性指数及肺组织病理学检查。结果再灌注后IR组和Sev IR组的肺组织W/D、TNFα、IL 1β的含量以及MPO的活性、肺通透性指数、BALF中白细胞数、中性粒细胞数均高于S组(P＜0.01)， Sev IR组减弱上述指标的升高(P＜0.05)；IR组和Sev IR组IL 10低于S组(P＜0.01)，而Sev IR组IL 10的含量明显高于IR组(P＜0.05)。病理学检查显示七氟醚预先给药减弱肺组织缺血 再灌注损伤的程度。结论七氟醚对肺缺血 再灌注损伤兔有保护作用，其机制可能与其抑制TNF α、IL 1β释放，升高IL 10的水平，抑制PMN的浸润有关。     

大鼠肝缺血再灌注后肺细胞凋亡及七氟醚对细胞凋亡及 NF-κBp65的影响

目的：探讨七氟醚预处理对大鼠肝缺血再灌注后肺细胞凋亡的影响。方法24只Wister大鼠随机分为3组（n＝8）：假手术组,缺血再灌注组,七氟醚组,阻断肝门30 min后建立大鼠70％肝缺血再灌注模型。假手术组（ S组）仅游离肝门,但不阻断;肝缺血再灌注组（ IR组）采用阻断肝门30 min,再灌注1 h的方法制备大鼠肝缺血再灌注损伤模型;七氟醚预处理组（ SP组）吸入2．1％七氟醚30 min,停止吸入10 min后制备肝缺血再灌注模型。于再灌注1 h时处死动物,留取肺组织,测定湿／干重比（ W／D比）,采用比色法检测超氧化物歧化酶（ SOD）活性及丙二醛（ MDA）含量,采用原位末端转移酶法（ TUNEL）检测细胞凋亡,计算细胞凋亡指数（ AI）,采用Western blot法测定核蛋白NF-κBp65表达,光镜下观察肺组织病理学结果。结果与S组比较,IR组和SP组再灌注各时点肺组织W／D比值、细胞凋亡指数（ AI）和NF-κB 活性水平及MDA含量均显著增高（均P＜0．05）;SOD活性显著降低（P＜0．05）;与IR组比较,SP组W／D比值、细胞凋亡指数（AI）、NF-κB表达水平与MDA含量显著降低（均P＜0．05）;而SOD活性显著增加（P＜0．05）;SP组肺组织损伤较IR组减轻。结论细胞凋亡可能在肝缺血再灌注肺损伤发生过程中具有重要意义;七氟醚对大鼠肝缺血再灌注后肺细胞凋亡具有抑制作用,其作用机制可能通过降低肺组织NF-κB的活性,从而清除自由基、抑制脂质过氧化有关。     

七氟醚对大鼠缺血再灌注心肌凋亡相关基因表达的影响

目的探讨七氟醚预处理对大鼠心脏缺血再灌注过程中心肌细胞Bcl-2及Bax基因表达的影响。方法24只SD大鼠随机分成3组（n=8）：假手术对照组（C组）、缺血再灌注对照组（IR组）和七氟醚预处理组（s组）。IR组与S组接受左冠脉3h阻断和3h再灌注。七氟醚预处理组在缺血前吸入七氟醚,30min后洗脱15min。取心肌缺血区组织,RT-PCR测Bcl-2及Bax基因的mRNA表达,免疫印迹法（Western-blot）测蛋白表达。结果与C组相比较,IR组和S组Bcl-2的mRNA和蛋白表达均下调,而S组高于IR组;Bax的mRNA和蛋白表达IR及S组均高于C组,IR组则高于S组。结论七氟醚预处理抑制心肌细胞凋亡可能与上调Bd-2基因的表达、下调Bax基因的表达有关。     

七氟烷对大鼠缺血再灌注后肺组织氧自由基的影响

目的通过建立在体大鼠肺缺血再灌注损伤模型,观察七氟烷对缺血再灌注后肺组织氧自由基(OFRs)表达的影响,探讨缺血再灌注后肺损伤和七氟烷肺保护的可能机制。方法选择96只雄性wistar大鼠,参照改良的Eppinger方法建立在体大鼠肺缺血再灌注损伤模型。共分4组,每组24只大鼠。C组:开胸游离左肺门,未行肺门阻断;IR组:阻断肺门45min后开放再灌注;Sev-C组:吸入1MAC七氟烷30min,游离肺门不阻断;Sev-IR组:吸入七氟烷30min后阻断左肺门45min,然后开放再灌注。每组包括3个时点:缺血阻断45min、再灌注60min、再灌注120min,每时点6只大鼠,另外再灌注120min时,各组另取6只大鼠行支气管灌洗。记录各时点MAP、SpO2,测定W/D、肺通透指数(LPI),生化法检测肺组织MDA、SOD和MPO含量。结果与C组和Sev-C组比较,IR组和Sev-IR组再灌注后W/D、LPI均上升(P<0.05),Sev-IR组W/D、LPI升高的程度低于IR组(P<0.05);IR组再灌注60min、120min肺组织MDA、MPO含量增加(P<0.05),SOD含量减少(P<0.05)。Sev-IR组MDA、MPO增加、SOD减少的程度都低于IR组(P<0.05)。结论肺缺血再灌注后血管通透性增加,再灌注后肺损伤的机制与OFRs产生过多有关,七氟烷预处理能抑制OFRs的生成,对再灌注后肺组织具有一定的保护作用。     

左旋精氨酸对兔肺缺血-再灌注损伤氧化应激与降钙素基因相关肽的影响

目的 探讨兔肺缺血 再灌注损伤时左旋精氨酸对氧化应激、降钙素基因相关肽（CGRP）的影响。方法 采用在体兔的缺血 再灌注损伤动物模型。雄性日本大耳兔30只，随机分成3组，每组10只：假手术对照组（S组）、缺血再灌注组（IR组）、左旋精氨酸+缺血再灌注组（L-Arg组）。分别在开胸前、缺血末、再灌注末从左颈外静脉采血，检测各组丙二醛（MDA）、一氧化氮（NO）和超氧化物歧化酶（SOD）活力和CGRP含量。结果 L-Arg组在缺血末及再灌注末SOD活力及NO含量明显高于S组及IR组（均P＜0.01），而IR组缺血末及再灌注末与S组比较均有所下降（均P＜0.05）。在再灌注末，IR组MDA含量明显高于S组和L-Arg组(均P＜0.05)，而CGRP含量却明显低于S组和L-Arg组(均P＜0.01)。结论 左旋精氨酸可能通过诱导SOD和CGRP的生成对兔肺组织的缺血 再灌注损伤起保护作用。     

乳化异氟醚预处理对大鼠肺缺血再灌注损伤的保护作用

目的探讨乳化异氟醚预处理对大鼠肺缺血再灌注损伤的保护作用。方法雄性Wistar大鼠160只,体重250～300g,随机分为5组,每组32只,对照组(A组)、假手术组(B组)、缺血再灌注模型组(C组)、脂肪乳组(D组),乳化异氟醚预处理组(E组)。对照组不作任何处理;假手术组仅开胸游离左肺门后,不进行阻断左肺门,用生理盐水5mL/(kg.h)输注30min;缺血再灌注组(I/R组):开胸游离左肺门后,用生理盐水5mL/(kg.h)输注30min后,阻断左肺门45min,后松开血管夹形成再灌注;脂肪乳组用30%浓度的脂肪乳5mL/(kg.h)输注30min后,阻断左肺门45min,后松开血管夹形成再灌注;乳化异氟醚组用6.9%乳化异氟醚5mL/(kg.h)静脉注射30min后,阻断左肺门45min,后松开血管夹形成再灌注。观察各组大鼠肺组织病理学,测定肺组织匀浆MPO、TNF-α水平。结果肺缺血再灌注可导致严重的肺组织损伤,表现为肺组织有明显的水肿、渗出和炎性细胞浸润。与A、B组相比,C组肺组织各时间点MPO和TNF-α活性增强(P0.05)。与C组相比,乳化异氟醚预处理组(E组)肺组织的病理表现及损伤程度明显减轻,肺组织各时间点MPO和TNF-α水平降低(P0.05)。结论肺缺血再灌注可引起严重的肺损伤;乳化异氟醚预处理对大鼠肺缺血再灌注损伤的具有保护作用。     

七氟醚预处理对局灶性脑缺血/再灌注后早期大鼠空间学习与记忆能力的影响

目的观察七氟醚预处理对局灶性脑缺血/再灌注后大鼠空间学习与记忆能力的影响。方法♂SD大鼠24只,随机分成假手术(C)组、缺血/再灌注组(I/R)和七氟醚预处理组(S),每组8只。采用线栓法行大脑中动脉阻断前脑血供1 h,拔出栓线实现再灌注。七氟醚预处理组术前吸入七氟醚1 h(呼气末浓度维持在1.0 MAC)。再灌注72 h后利用Morris水迷宫测量术后大鼠空间学习与记忆的能力,用HE染色法测定大鼠海马CA1区锥体细胞数目的变化。结果七氟醚预处理组大鼠逃避潜伏期明显短于缺血/再灌注组(P<0.05),在记忆保留实验中七氟醚预处理组大鼠穿越平台次数和平台所在象限探索时间明显多于缺血/再灌注组(P<0.05),海马CA1区的锥体细胞数目七氟醚预处理组也明显多于缺血/再灌注组(P<0.05)。结论1.0 MAC七氟醚预处理1 h可能通过保护CA1区锥体细胞,对局灶性缺血/再灌注大鼠的空间学习与记忆有明显的改善作用。     

氟醚预处理对局灶性脑缺血/再灌注后早期大鼠空间学习与记忆能力的影响

目的 观察七氟醚预处理对局灶性脑缺血/再灌注后大鼠空间学习与记忆能力的影响.方法 ♂ SD大鼠24只,随机分成假手术(C)组、缺血/再灌注组(I/R)和七氟醚预处理组(S),每组8只.采用线栓法行大脑中动脉阻断前脑血供1 h, 拔出栓线实现再灌注.七氟醚预处理组术前吸入七氟醚1 h(呼气末浓度维持在1.0 MAC).再灌注72 h后利用Morris水迷宫测量术后大鼠空间学习与记忆的能力,用HE染色法测定大鼠海马CA1区锥体细胞数目的 变化.结果 七氟醚预处理组大鼠逃避潜伏期明显短于缺血/再灌注组(P<0.05),在记忆保留实验中七氟醚预处理组大鼠穿越平台次数和平台所在象限探索时间明显多于缺血/再灌注组(P<0.05),海马CA1区的锥体细胞数目七氟醚预处理组也明显多于缺血/再灌注组(P<0.05).结果 1.0 MAC七氟醚预处理1 h可能通过保护CA1区锥体细胞,对局灶性缺血/再灌注大鼠的空间学习与记忆有明显的改善作用.     

七氟醚预处理对兔缺血再灌注心肌组织保护作用的机制

目的探讨七氟醚预处理对缺血再灌注心肌组织保护作用的机制。方法应用24只新西兰白兔制备心肌缺血再灌注损伤模型,后将其随机分成对照组、缺血预处理组、七氟醚预处理组3组,每组8只。取3组动物心肌组织做组织切片,免疫组织化学方法观察3组心肌细胞内Bcl-2水平的表达,利用HPIAS-2000图像分析系统测定Bcl-2表达的平均光密度和平均阳性面积率。结果Bcl-2在缺血预处理组和七氟醚预处理组心肌细胞内的表达高于对照组,差异有统计学意义（P〈0．01）;缺血预处理组心肌细胞内Bcl-2表达水平与七氟醚预处理组比较差异无统计学意义（P〉0．05）。结论七氟醚预处理对缺血再灌注的在体兔心肌具有重要的保护作用。     

转化生长因子β_1、细胞间黏附分子1在大鼠肺缺血再灌注损伤中的作用

目的 观察大鼠肺缺血再灌注中内源性转化生长因子β1(TGF-β1)和细胞间黏附分子1(ICAM-1)在肺缺血中的作用.方法 采用60只SD大鼠建立肺缺血再灌注模型,分为假手术组(S),再灌注组(IR),每组又分为0、1、2、4、8 h五个亚组.检测TGF-β1,ICAM-1及髓过氧化物酶(MPO)含量.结果 S组TGF-β1、ICAM-1只有少量表达;IR组TGF-β1和ICAM-1于再灌注后明显高于S组,MPO含量在IR组缺血再灌注后亦明显比S组增加(P＜0.05或P＜0.01).结论 TGF-β1参与肺缺血再灌注损伤后的修复,而ICAM-1参与肺缺血再灌注损伤后的损伤.     

在ARDS中开放的肺部

Every year, millions of patients worldwide receive ventilator support during surgery. Mechanical ventilation has become an important therapy in the treatment of patients with impaired pulmonary function and particularly in patients suffering from adult respiratory distress syndrome (ARDS). ARDS is caused by multiple factors and is characterized by respiratory dysfunction including hypoxemia and decreased lung compliance. It is known that the decrease in lung distensibility is due to a disturbed surfactant system with an elevated surface tension. This increase in surface tension leads to an increase in forces acting at the air-liquid interface, resulting finally in endexpiratory collapse, atelectasis, an increase in right-to-left shunt and a decrease in PaO2.     

Lactate dehydrogenase isoenzymes in hamster lung lavage fluid after lung injury

Lactate dehydrogenase (LD) levels and isoenzyme patterns were determined in the cell-free supernatant fractions of lung lavage fluid from hamsters exposed to alpha-quartz, iron oxide, Triton X-100, 100% O₂, or 200 ppm SO₂. The isoenzyme patterns were compared to those derived from hamster lung homogenates, serum, polymorphonuclear neutrophils (PMNs), pulmonary macrophages, and red blood cells. The isoenzyme patterns from alpha-quartz- and iron oxide-exposed animals resembled each other and were similar to that of PMNs. In contrast, the pattern seen after Triton X-100 exposure was similar to those of whole lung homogenates and of red blood cells. A 96-hr exposure to 100% O₂ yielded an LD isoenzyme pattern in lung lavage fluid similar to that of serum. Exposure to SO₂ did not alter LD levels, showing that upper airways damage is not reflected by changes in LD in lung lavage fluid. We conclude that LD isoenzyme patterns of lung lavage fluid can be used to differentiate among types of pulmonary injury and may help identify the sites of injury.     

Erlotinib in non-small-cell lung cancer

Epidermal growth factor receptor (EGFR) plays an essential role in normal cell growth and differentiation, and is involved in tumour proliferation and survival. EGFR overexpression is a common feature in solid malignancies, including non-small-cell lung cancer (NSCLC), and is associated with poor clinical prognosis. Erlotinib is a small-molecule inhibitor of EGFR tyrosine kinase, showing a significant improvement in median survival, quality of life and related symptoms in an unselected population of advanced NSCLC patients in the second- or third-line setting. Erlotinib is well tolerated (with common toxicities including rash and diarrhoea) when administered at a standard oral daily dose of 150 mg. Further investigations are ongoing to contribute to our understanding of the role of erlotinib in NSCLC treatment.     

Emerging drugs in lung transplantation

The balance between immunosuppression to ensure graft tolerance while preventing emergence of infectious complications is key in lung transplantation. Although opportunistic infection may appear to be the most important of these complications, malignancies and severe drug toxicities significantly affect the short- and long-term outcomes of the patients. The present practice is combination therapy using drugs with complementary immunosuppressive action, to achieve synergistic immunosuppression with the lowest possible toxicity. Components of immunosuppression include induction and maintenance regimens. Primary graft failure remains an important cause of mortality and morbidity in the immediate post-transplant period. Acute rejection is a common complication after lung transplant, but responds well to augmented immunosuppression and immunomodulation. Chronic rejection still is the major cause of mortality in patients who survive the initial year post-transplantation. Several new drugs have shown promise in decreasing the rate of loss of graft function. This review discusses the current and emerging therapeutic regimens.     

Ciclosporin aerosol in lung transplantation

The development of ciclosporin as an aerosol for rejection immunosuppression following lung transplantation started as a research idea at the University of Pittsburgh in 1989. In the 17 subsequent years, the development of the aerosol, testing in animals and several protocols testing the drug in patients have all taken place at the University of Pittsburgh and State University of New York. No other medical advances have displaced the potential of the drug during this time in lung transplantation, which still has a dismal 5-year survival of 50%. Therefore, the recent publication of the double-blind, placebo-controlled study of aerosolised ciclosporin for long-term use to significantly improve patient survival was heralded as a breakthrough by the commentary in the New England Journal of Medicine. Nevertheless, multiple problems may prevent this drug from ever receiving FDA approval and reaching the market. These problems include the need for a multi-centre study, a lack of surrogate markers for chronic rejection in lung transplant patients and a drug formulation that will prevent the expansion of the use of aerosolised ciclosporin for other indications.     

肺干细胞的研究进展

肺干细胞(lung stem cells)是指在特定条件下能分化为功能性肺组织,在维持肺组织更新和肺损伤修复中起着重要作用的细胞。近年来对肺干细胞的研究已取得了很大的进展,该文就肺干细胞的来源、分离方法、应用以及肺癌干细胞等方面的研究进展作如下综述。     

肺挫伤及肺撕裂伤的CT诊断

目的:探讨肺挫伤及肺撕裂伤的CT影像学表现及诊断价值。方法:回顾性分析收治的48例肺挫伤及肺撕裂伤患者的临床特点及CT表现。结果:48例胸部外伤病例中,26例有肺挫伤损伤(上肺3例,下肺17例,双肺6例),22例有肺撕裂伤(14例肺水肿,8例肺内血气囊肿)。结论:CT成像技术可全面显示病变征象及范围,应用于肺挫伤及肺撕裂伤患者的诊断。     

热毒宁注射液对急性肺损伤家兔肺表面活性物质的影响

目的:研究热毒宁注射液(RDN)对急性肺损伤(ALI)家兔肺表面活性物质磷脂酰胆碱含量(PC)的影响.方法:健康家兔分3组,静脉注射内毒素(主要成分为脂多糖,LPS)建立ALI模型,应用RDN治疗后,不同时间点检测外周血及支气管肺泡灌洗液(BALF)内白介素-8,10(IL-8,IL-10),肿瘤坏死因子(TNF-α)的含量,并测定BALF内PC的含量.结果:LPS诱导的ALI家兔中,血和BALF中的致炎因子含量较正常对照组显著升高,肺通透指数升高,PC较正常对照组显著下降[(6.43±2.44)vs(4.24±0.93)mg·g-1,P<0.01].与模型组比较,RDN治疗组可显著逆转上述各指标的异常变化,PC显著升高[(4.24±0.93)vs(5.91±2.04)mg·g1-,P<0.05].结论:RDN对家兔ALI有一定的治疗作用,作用机制不仅与抑制致炎因子的活性有关,还可能与增加ALI家兔肺表面活性物质PC的含量有关.     

Heart and lung transplantation in patients with end stage lung disease.

Combined heart and lung transplantation was used to treat seven patients with end stage lung disease. All were severely disabled, and their disease carried a poor prognosis. Six patients were well four to 33 months after transplantation. One patient died after 44 days from a primary cytomegalovirus pneumonia transmitted from the donor. All the survivors had normal exercise tolerance and greatly improved lung function. It is concluded that heart and lung transplantation is a suitable treatment for selected patients with end stage chronic lung disease.