白细胞介素8和一氧化氮在家兔内毒素性急性肺损伤中的作用

目的和方法：采用间隔２４ｈ两次注射大肠杆菌内毒素（ＥＴ）的方法，复制家兔内毒素性急性肺损伤模型，探讨肺损伤的机理。结果：ＥＴ组血浆、肺组织匀浆及支气肺泡灌洗液（ＢＡＬＦ）中白细胞介素８（ＩＬ－８）、亚硝酸／硝酸根离子（ＮＯ２－／ＮＯ３－）水平显著增高（Ｐ＜００１），血浆补体Ｃ５ａ活性明显增高（Ｐ＜００１），ＢＡＬＦ内中性粒细胞明显增多，肺系数、肺水含量及通透指数升高。ＩＬ－８、ＮＯ２－／ＮＯ３－水平以及血清和ＢＡＬＦ中酸性磷酸酶活性变化高度相关。结论：ＩＬ－８、一氧化氮（ＮＯ）参与内毒素性急性肺损伤，而ＩＬ－８是造成肺损伤的重要中间环节。     

胆囊收缩素对内毒素性休克大鼠SOD,MDA及吞噬细胞发光的影响

以ＳＤ大鼠ＥＳ（内毒素休克，内毒素０．８ｍｇ／１００ｇｂ．ｗ．ｉｖ）为模型，观察了ＣＣＫ－８抗ＥＳ过程中平均动脉血压（ＭＡＰ）血液超氧化物歧化酶（ＳＯＤ）脂质过氧化产物二醛（ＭＤＡ）及吞噬细胞化学发光（ＰＣＬ）的变化，实验结果：ＣＣＫ－８可使ＥＳ大鼠ＭＡＰ回升，血浆ＳＯＤ活性升高（Ｐ〈０．０１），ＭＤＡ含量减少（Ｐ〈０．０５），吞噬细胞本底发光增强，峰值增高，峰时缩短（Ｐ〈０．０５），结果表明ＣＣ     

白细胞介素8和一氧化氮在家兔内毒素性急性损伤中的作用

目的和方法：采用间隔２４ｈ两次注射大肠杆菌内毒素（ＥＴ）的方法，复制家兔内毒素性急性肺损伤模型，探讨肺损伤的机理，结果：ＥＴ组血浆，肺组织匀浆及支气肺泡灌洗液中白细胞介素８（ＩＬ－８），亚硝酸／硝酸根离子显著增高（Ｐ〈０．０１），血浆补体Ｃ５ａ活性明显增高（Ｐ〈０．０１），ＢＡＬＦ内中性粒细胞明显增多，肺系数，肺水含量及通透指数升高，ＩＬ－８，ＮＯ２＾－／ＮＯ３＾－水平以及血清和ＢＡＬＦ中酸性磷酸     

异丙嗪对家兔内毒素性发热及血清SOD和MDA含量的影响

目的：观察异丙嗪对家兔内毒素性发热及血清超氧化物歧化酶（ＳＯＤ）和脂质过氧化物丙二醛（ＭＤＡ）含量的影响。方法：复制家兔内毒素性发热模型，用黄嘌呤氧化酶法测定血清ＳＯＤ的活性，用改良巴比妥酸微量法测定血清ＭＤＡ的含量。结果：异丙嗪不仅完全抑制内毒素性发热，而且降低正常体温，该剂量的内毒素引起发热时，血清ＳＯＤ活性和ＭＤＡ含量未见明显改变，而静脉注射异丙嗪（２５ｍｇ／ｋｇ）却引起血清ＳＯＤ活性降低（Ｐ＜００５）和ＭＤＡ含量明显升高（Ｐ＜００５）。结论：在本实验条件下，内毒素性发热时血清自由基水平未见明显改变，而该剂量的异丙嗪有显著抑制内毒素性发热的作用并影响血清ＳＯＤ和ＭＤＡ的产生和代谢     

内毒素、地塞米松对体外培养大鼠肺泡巨噬细胞中NF_(-k)B活化的影响

目的 探讨内毒素（ＬＰＳ）和地塞米松（Ｄｅｘ）对体外培养的大鼠肺泡巨噬细胞（ＡＭ）中ＮＦ－ＫＢ活化的影响，以及ＡＭ中ＮＦ－ＫＢ活化在急性肺损伤中的可能作用。方法 通过建立大鼠ＡＭ体外培养技术，应用免疫组化染色法，观察ＬＰＳ和Ｄｅｘ寸 ＡＭ中 ＮＫ－ＫＢＰ～（６５），ＩＫＢ－α、ＴＮＦ－α和 ＩＣＡＭ－ｌ蛋白表达的动态变化。结果 ＬＰＳ能使培养的ＡＭ中 ＮＦ－ＫＢＰ～（６５），ＴＮＦ－α和ＩＣＡＭ－ｌ的表达增加，ＩＫＢ－α的表达降低；Ｄｅｘ的作用与 ＬＰＳ恰相反。结论ＬＰＳ促进ＡＭ中的ＮＦ－ＫＢ活化，可能是急性肺损伤肺内炎症损害发生的启动及促进因素；Ｄｅｘ抑制 ＮＦ－ＫＢ的活化，可能是其抗炎作用的重要机制之一。     

地塞米松对内毒素急性肺损伤磷脂酶A2活性变化的影响

实验采用绵羊慢性肺淋巴瘘－内毒素急性肺损伤模型，检测了肺组织磷脂酶Ａ２（ＰＬＡ２）活性及有关指标改变，并观察了地塞米松（Ｄｅｘ）对ＰＬＡ２活性变化的影响。结果发现，内毒素致伤后肺组织ＰＬＡ２活性及血栓素Ｂ２（ＴＸＢ２）、前列环素（６－Ｋｅｏｔｏ－ＰＧＦ１ａ）水平明显升高（Ｐ＜０．０１），致伤后２、４、６ｈＰＬＡ２活性分别为致伤前的１．９、２．８和３．３倍，肺动脉压（Ｐｐａ）和肺淋巴流量明显升高。应     

绵羊内毒素肺损伤时P物质和前列腺素含量变化

本实验利用较大剂量内毒素在带慢性肺淋巴瘘的清醒绵羊复制肺损伤模型。测定了动物血浆、肺淋巴液中P物质(SP)、血栓烷B_2(TXB_2)和6-酮前列腺素F_(1α)(6-keto-PGF_(1α))含量变化及肺组织中SP含量改变。结果显示,注入内毒素后120min,血浆和肺淋巴液SP含量明显高于注射内毒素前。在注入内毒素后360min,肺组织中SP含量则显著低于注射前。注入内毒素后30min,血浆TXB_2和6-keto-PGF_(1α)显著升高。肺淋巴液中TXB_2和6-keto-PGF_(1α)于注入内毒素后60min显著高于注射内毒素前,且TXB_2比6-keto-PGF_(1α)升高更明显。     

兔盲肠结扎穿孔早期一氧化氮抗肺动脉压增高和抗氧化作用

目的和方法：采用家兔盲肠结扎穿孔（ＣＬＰ）模型观察了ＣＬＰ前后以及一氧化氮（ＮＯ）合成抑制剂左旋硝基精氨酸（Ｌ－ＮＮＡ）对平均动脉血压（ＭＡＰ），肺动脉压（ＰＡＰ），入、出肺血ＮＯ、丙二醛（ＭＤＡ）含量和超氧化物歧化酶（ＳＯＤ）活性的改变。结果：兔ＣＬＰ后１～５ｈＭＡＰ明显下降，而在２、２５ｈ出现ＰＡＰ明显升高。ＣＬＰ前出肺血ＮＯ含量显著低于入肺血，ＣＬＰ后２５ｈ入肺血ＮＯ含量低于ＣＬＰ前，而出肺血ＮＯ含量与ＣＬＰ前相比无明显差异，且入、出肺血ＮＯ含量无明显差异。ＣＬＰ后２５ｈ入肺血ＭＤＡ含量比ＣＬＰ前有明显增加，出肺血无显著改变；而出肺血ＳＯＤ活性比ＣＬＰ前有明显增高，入肺血无显著改变。注入Ｌ－ＮＮＡ后入、出肺血ＮＯ含量明显降低，各时点ＰＡＰ都明显增高，５ｈ生存率降低，同时入、出肺血ＭＤＡ含量明显升高，ＳＯＤ活性明显下降。结论：肺内ＮＯ含量改变可能与氧自由基有关，在兔ＣＬＰ后早期阶段ＮＯ具抗肺动脉高压和抗氧化的作用     

地塞米松对内毒素肺损伤时血管活性肠肽含量的影响

地塞米松对内毒素肺损伤时血管活性肠肽含量的影响西安第四军医大学西京医院呼吸内科（７１００１５）王钧，孙滨，刘林英，王佐忠本实验对绵羊内毒素肺损伤及应用糖皮质激素治疗过程中动物血浆，肺淋巴液中血管活性肠肽（ｖａｓｏ－ａｃｔｉｖｅｉｎｔｅｓｔｉｎａｌｐｅ...     

缺氧大鼠肺组织氧化／抗氧化平衡的变化及其与TXA_2／PGI_2平衡的关系

检测缺氧大鼠肺组织丙二醛（ＭＤＡ）、超氧化物歧化酶（ＳＯＤ）和过氧化氢酶（ＣＡＴ）含量以及血浆ＴＸＡ＿２和ＰＧＩ＿２浓度，以探讨氧自由基（ＯＦＲ）及ＴＸＡ＿－ＰＧＩ＿２在缺氧性肺动脉高压中的作用。结果表明：与对照组比较缺氧大鼠肺组织ＭＤＡ明显升高、ＳＯＤ、ＣＡＴ明显降低，ＶｉｔＥ可逆转ＭＤＡ和ＳＯＤ的变化；缺氧大鼠血浆ＴＸＢ＿２高于对照组，其浓度与肺组织ＭＤＡ含量呈正相关（ｒ＝０．６５．Ｐ＜０．０５）。以上结果提示，ＯＦＲ与ＴＸＡ＿２／ＰＲＩ＿２平衡失调相互作用，可能共同参与缺氧性肺动脉高压的发生。     

活性氧在急性肺损伤中的作用

采用清醒绵羊—慢性肺淋巴瘘—内毒素急性肺损伤模型,测定了不同来源标本中几种活性氧含量的变化。结果,内毒素致伤后呼出气冷凝液中H_2O_2浓度增加1倍(P<0.01),动脉血,肺淋巴液和肺泡灌洗液中脂质过氧化物浓度显著增加(P<0.01),动脉血浆和肺淋巴液诱发化学发光显著增强(P<0.01)。表明活性氧在内毒素肺损伤中起重要作用,直接来自肺的标本中活性氧产物的检测,可敏感地反映急性肺损伤。     

急性肺血栓栓塞症兔TNF-α、IL-8、IL-10水平及地塞米松的影响

目的:探讨兔急性肺血栓栓塞症(PTE)时血浆及支气管肺泡灌洗液(BALF)中TNF-α,IL-8、IL-10的水平和地塞米松(Dex)的影响。方法:采用自体血栓回输法建立兔急性PTF模型。36只兔随机分为对照组、Dex治疗组和PTE模型组。用ELISA方法检测上述细胞因子(CK)水平,术毕肺组织行病理观察。结果:栓塞后上述CK均有升高,治疗后TNF-α、IL-8均有下降,IL-10变化不明显。组织病理学可见栓塞后肺动脉内血栓形成,肺组织萎缩、出血、炎性反应明显,Dex治疗后肺组织病理改变明显减轻。结论:PTE后促炎性CK在引起肺部炎性反应和肺组织及肺动脉病损中起了重要作用,抗炎治疗可以明显减轻CK引起的这种损伤。抗炎治疗能降低PTE急性期病死率,改善远期预后,CK可能起了很重要的作用。     

地塞米松对急性肺损伤中TREM-1表达的影响

目的　探讨地塞米松（Dexamethasone,Dex）对脂多糖（Lipopolysaccharide, LPS）诱导的急性肺损伤(acute lung injury, ALI)小鼠肺组织中髓样细胞表达的触发受体1（triggering receptor expressed on myeloid cells-1,TREM-1）表达的影响。 方法　以昆明小鼠为研究对象,腹腔注射LPS(10 mg/kg)建立ALI模型,30 min后给予不同浓度的Dex（5、10、20、40 mg/kg）处理6 h;选用Dex(10 mg/kg)处理不同的时间（6、12、24、36 h）。HE染色法观察肺组织病理损伤程度; RT-PCR检测肺组织TREM-1mRNA的表达;ELISA检测小鼠支气管肺泡灌洗液中可溶性TREM-1（sTREM-1）蛋白水平。 结果　Dex可减轻肺病理损伤;Dex呈时间依赖性地下调ALI小鼠肺组织的TREM-1 mRNA的表达,且在6 h即可降低;Dex呈剂量依赖地下调ALI小鼠肺组织中TREM-1 mRNA的表达,并在10 mg/kg时开始降低。Dex可降低ALI小鼠支气管肺泡灌洗液中sTREM-1的蛋白水平。 结论　Dex可呈剂量及时间依赖性下调ALI小鼠肺组织中的TREM-1mRNA的表达,并减少肺内髓样细胞胞膜TREM-1的脱落,提示Dex可能通过调节TREM-1的表达,从而抑制ALI早期的炎症级联反应,参与保护肺组织。     

牛磺酸对家兔油酸肺损伤的防治作用

目的：观察肺损伤家兔血浆丙二醛（ＭＤＡ）含量、红细胞超氧化物歧化酶（ＳＯＤ）活性变化以及牛磺酸的影响作用。方法：实验用油酸复制肺损伤模型。结果：（地）家兔注射油酸后１５ｍｉｎ时血浆ＭＤＡ含量显著增加,而红细胞ＳＯＤ活性显著下降。（２）牛磺酸可减轻上述变化。结论：提示牛磺酸对于急性肺损伤可能具有一定防治作用,其机制可能与抗自由基有关。     

内毒素性急性肺损伤大鼠白细胞介素—6含量改变

采用白细胞介素－６（Ｉｎｔｅｒｌｅｕｋｉｎ６，ＩＬ－６）依赖细胞株７ＴＤ１及ＭＴＴ比色法，动态观察了正常及内毒素注射后不同时间大鼠血清和支气管肺泡灌洗液（ｂｒｏｎｃｈｏａｌｏａｌｖｅｏｌａｒｌａｖａｇｅｆｌｕｉｄ，ＢＡＬＦ）中ＩＬ－６含量的变化。同时，还对各组大鼠的肺体指数和ＢＡＬＦ中蛋白质含量进行了测定，结果显示：大鼠注射内毒素后１，３，６，１２ｈ其血清和ＢＡＬＦ中ＩＬ－６含量急剧升高（Ｐ〈０．     

Quantitative assessment of microvascular permeability in endotoxin-induced lung injury in anaesthetized dogs

We quantitatively assessed the change of pulmonary microvascular permeability following E. coli endotoxin infusion (1 mg/kg) in anaesthetized dogs. We used mathematical analysis to estimate membrane parameters from lung lymph data. Lung lymph was collected from the afferent lymphatic connecting to the left tracheobronchial lymph node whose lymph could be considered to represent an average sample of lung tissue fluid. To separate the effects of changes in the driving pressures and surface area on lymph fluid and protein flux from those in membrane permeability, lymph flow (Jv) was increased greater than 6 times baseline by left atrial pressure (Pla) elevation until lymph protein concentration (CL) approached to a constant value independent of Jv. Membrane parameters for plasma total protein, i.e., osmotic reflection coefficient (sigma d), solvent-drag reflection coefficient (sigma f), permeability surface area product (PS), filtration coefficient (Kfc), were calculated from lung lymphatic data in control (Pla elevation alone (n = 10), and endotoxin group (n = 7). Among these parameters, osmotic reflection coefficient (sigma d) decreased significantly to 0.61 in endotoxin group from the value of 0.71 in control group. This result indicates a moderate increase in pulmonary microvascular permeability following E. coli endotoxin infusion. However, there was no significant difference in the other membrane parameters (sigma f, PS, Kfc) between control and endotoxin group. Based on these results, we conclude that sigma d could quantitatively represent the moderate change of the microvascular permeability in endotoxin-induced lung injury in anaesthetized dogs.     

Effect of tacrolimus on endotoxin-induced lung injury in sheep

Since tacrolimus (FK-506) is known to suppress the proliferation and generation of T cells and to inhibit the production of T cell derived cytokines, we examined the effect of FK-506 on endotoxin-induced lung injury. We administered FK-506 (0.1 mg/kg) intravenously before the infusion of endotoxin (1 microgram/kg) into conscious sheep. We measured pulmonary hemodynamics, lung fluid balance, circulating leukocyte count and arterial blood gas tensions. The increase in pulmonary arterial pressure was significantly attenuated by FK-506 during the late period (3-5 h after endotoxin). Arterial oxygen gas tension was significantly higher in the FK-506 treated sheep during this phase. However, no significant differences were observed in lung lymph balance and circulating leukocyte count between the endotoxin alone group and the FK-506 treated group. These findings suggest that FK-506 may improve gas exchange in acute lung injury although there is an increased pulmonary vascular leakage. It is probable that FK-506 may have a beneficial potential on endotoxin-induced lung injury in sheep.     

氨基胍对内毒素诱发的兔急性肺损伤的影响

目的:观察氨基胍(AG)对内毒素(ET)诱发的兔急性肺损伤(ALI)血流动力学及肺血管壁通透性的影响。方法:24只健康成年兔被均分为4组,生理盐水组、ET组、AG组和ET+AG组。ET+AG组先静脉注射ET,复制ALI模型,再以25mg/kg的剂量静脉滴注AG,共维持3h,观察不同时点平均动脉压(MAP)、平均肺动脉压(MPAP)和动脉血液气体参数的变化。实验结束后行支气管肺泡灌洗,测肺湿重/干重比率并常规留取肺标本。结果:ET组MAP下降,MPAP明显升高,动脉血氧分压下降;持续静滴AG后MAP无明显变化,但MPAP明显降低,血红蛋白氧合状况明显改善;AG可减少支气管肺泡灌洗液(BALF)中细胞数量;虽然BALF中蛋白含量无显著变化,但BALF电泳分析表明AG可明显减少小分子量蛋白的渗出;ET+AG组肺湿重/干重比率较ET组明显小;病理组织化学观察表明ET+AG组兔肺内炎症细胞渗出较少,肺水肿较ET组减轻。结论:AG可改善兔ALI血流动力学,减轻肺损伤。     

Effects of pretreatment with SDZ MRL 953, a novel immunostimulatory lipid A analog, on endotoxin-induced acute lung injury in guinea pigs.

SDZ MRL 953 (SDZ), a novel immunostimulatory lipid A analog, has been reported to have immunopharmacological activities similar to those of lipopolysaccharide (LPS) but to have little of the toxicity of LPS. We investigated the effects of pretreatment with SDZ on Escherichia coli endotoxin-induced acute lung injury in guinea pigs. Four experimental groups consisted of saline control (n = 16), SDZ (-12 h) plus LPS (2 mg/kg of SDZ per kg of body weight injected intravenously 12 h before intravenous injection of 2 mg of LPS per kg; n = 15), SDZ (-10 min) plus LPS (SDZ injected 10 min before LPS injection; n = 10), and LPS alone (n = 16). The animals were sacrificed, and lung tissue was sampled 4 h after LPS or saline infusion. Lung injury was assessed by measuring the wet weight-to-dry weight ratio and the level of 125I-labeled albumin accumulation in bronchoalveolar lavage fluid relative to that in plasma. In the SDZ (-12 h) plus LPS group, these two parameters of acute lung injury were decreased compared with those in the LPS alone group. However, they were not decreased in the SDZ (-10 min) plus LPS group. We conclude that SDZ attenuates endotoxin-induced acute lung injury when it is administered 12 h before LPS injection. The attenuating effects of SDZ are speculated to be due to down regulation of the response to endotoxin rather than to receptor blocking.