三羟异黄酮预先给药对内毒素诱导大鼠急性肺损伤的保护作用

目的研究三羟异黄酮预先给药对内毒素诱导大鼠急性肺损伤的保护作用及其机制。方法 32只雄性Wistar大鼠,随机分为4组,每组8只:对照组(C组)、三羟异黄酮组(G组)分别腹腔注射生理盐水1 ml／kg、三羟异黄酮50 mg／kg,30 min后,静脉注射生理盐水1 ml／kg;内毒素组(L组)、三羟异黄酮预预先给药组(Gpre组)分别腹腔注射生理盐水1 ml／kg、三羟异黄酮50 mg／kg,30 min后,静脉注射脂多糖6 mg／kg。注射脂多糖后4 h处死动物。测定支气管肺泡灌洗液(BALF)中蛋白浓度、髓过氧化物酶(MPO)活性及中性粒细胞(PMN)数。检测肺组织湿干重比(W／D)、丙二醛(MDA)含量、MPO 活性、肿瘤坏死因子-α(TNF-α)和血红素氧合酶-1(HO-1)mRNA、蛋白表达。观察肺组织病理学的改变。结果与C组比较,L组肺损伤严重、BALF中蛋白、MPO、PMN水平和肺组织W／D、MDA及MPO水平及TNF-α和HO-1 mRNA、蛋白表达水平升高(P<0．05或0．01),G组上述指标差异均无统计学意义(P >0．05);与L组比较,Gpre组除HO-1 mRNA、蛋白表达水平升高(P<0．05)外,其他指标均降低(P< 0．05或0．01)。结论三羟异黄酮预先给药对内毒素诱导大鼠急性肺损伤有一定的保护作用,与抑制PMN在肺组织的聚集、激活,TNF-α表达下调及HO-1表达上调有关。     

内毒素性肺损伤外周血中性粒细胞CD11b表达的意义

目的：探讨内毒素血症大鼠外周血中性粒细胞（PMN）表面CD11b表达与内毒素性肺损伤的关系。方法：大肠杆菌E-Coli O111B4 4mg／kg尾静脉注射制备大鼠内毒素血症动物模型。112只大鼠随机分为对照组（静脉注射等量生理盐水）及内毒素注射后1h组、2h组、4h组、8h组、12h组、24h组,每组16只动物。在相应时间点放血处死动物,分别取股静脉血、肺组织及进行支气管肺泡灌洗,测定肺组织湿／干重（W／D）比值、肺组织髓过氧化物酶（MPO）活性和支气管肺泡灌洗液（BALF）总蛋白定量等肺损伤指标。流式细胞仪测定外周血PMN表面CD11b表达。另取16只大鼠,内毒素注射后2h时测定外周血PMN表面CD11b表达,24h时放血处死,测定上述指标。结果：①大鼠内毒素血症可以造成明显的急性肺损伤,表现为肺组织W／D比值、MPO活性和BALF总蛋白明显增高,分别在2h、8h和2h显著高于对照组（P〈0．05或P〈0．01）,峰值分别出现在内毒素注射后12h、24h和12h;②大鼠内毒素性肺损伤时,外周血PMN表面CD11b表达水平在早期（1h）明显升高（与对照组比较,P〈O．05）,在2h达到峰值,之后逐渐降低;③外周血CD11b表达峰值明显早于肺组织W／D比、MPO和BALF总蛋白等肺损伤指标的峰值出现时间;④同一动物2h时外周血PMN表面CD11b的表达水平与其24h时肺组织W／D比、MPO和BALF总蛋白含量呈显著正相关（r分别为0．78、0．77和0．73,P〈0．05）。结论：内毒素性肺损伤中,外周血CD11b表达升高可能有助于内毒素性肺损伤的早期诊断,并可能预示以后的肺损伤程度。     

罗格列酮预先给药对内毒素诱导大鼠急性肺损伤的保护作用

目的 研究过氧化物酶体增殖物激活受体γ(PPARγ)激动剂-罗格列酮预先给药对内 毒素(LPS)诱导急性肺损伤(ALI)的影响。方法 36只雄性Wistar大鼠,随机分为6组,每组6只:对 照组(DMSO)、ROSI、GW组分别静脉注射10％二甲基亚砜(DMSO)2 ml／kg、罗格列酮0．3 mg／kg或 GW9662 0．3 mg／kg,30 min后静脉注射生理盐水2 ml／kg;LPS、ROSI LPS组分别静脉注射10％DMSO、 罗格列酮0．3 mg／kg,30 min后静脉注射LPS 6 mg／kg;GW ROSI组处理同ROSI LPS组,但在给予罗格 列酮前20min静脉注射GW9662 0．3mg／kg。注射LPS后4 h处死大鼠,光镜下观察肺组织病理学变化, 测定肺组织湿／干重比(W／D)、髓过氧化物酶(MPO)活性、丙二醛(MDA)和一氧化氮(NO)含量,检测肺 组织诱导型NO合酶(iNOS)和硝基酪氨酸(NT)的蛋白表达。结果 与DMSO比较,LPS组肺损伤严 重,W／D、MPO活性、MDA和NO含量升高(P<0．01),肺组织iNOS、NT的蛋白表达增加(P<0．05或 0．01)。与LPS组比较,ROSI LPS组肺损伤明显减轻,W／D、MPO活性、MDA和NO含量降低(P< 0．01),肺组织iNOS和NT的蛋白表达减弱。PPARγ拮抗剂GW9662能逆转罗格列酮的作用。结论 罗格列酮预先给药对内毒素诱导的ALI具有一定的保护作用,其机制与激活PPARγ有关。     

七氟醚预处理对大鼠内毒素性急性肺损伤的影响

目的 探讨七氟醚预处理对大鼠内毒素性急性肺损伤的影响.方法 健康雄性SD大鼠24只,体重220～250 g,随机分为4组(n=6):对照组(c组)、内毒素组(LPS组)、七氟醚组(Sev组)和七氟醚预处理组(SP组).C组和LPS组机械通气30 min后分别静脉注射生理盐水和脂多糖(LPS)5 mg/kg;Sev组和SP组吸入七氟醚(呼气末浓度2.4%)30 min,洗脱5 min,然后分别静脉注射生理盐水和LPS 5 mg/kg.于给予LPS或生理盐水后6 h时,心脏放血处死大鼠,取肺组织,计算湿重/干重(W/D)比;采用弥漫性肺泡损伤(DAD)评分评价肺组织损伤程度;测定肺组织髓过氧化物酶(MPO)活性、细胞因子诱导中性粒细胞化学趋化因子-1(CINC-1)含量、CINC-1和CINC-1 mRNA的表达水平.结果 与C组比较,LPS组和SP组肺组织W/D比、DAD评分、MPO活性和CINC-1含量升高,CINC-1和CINC-1 mRNA的表达上调(P<0.01),Sev组上述指标差异无统计学意义(P>0.05);与LPS组比较,SP组肺组织W/D比、DAD评分、MPO活性和CINC-1含量降低,CINC-1和CINC-1 mRNA的表达下调(P<0.01).结论 七氟醚预处理可减轻大鼠内毒素性急性肺损伤,可能与其抑制肺组织炎性反应有关.     

异氟醚对大鼠肺缺血再灌注损伤的保护作用

目的 探讨异氟醚对大鼠肺缺血再灌注损伤的保护作用。方法 120只SD雄性大鼠，随机分成4组（n=30）：假手术组（S组）、缺血再灌注组（IR组）、异氟醚-缺血再灌注组（ISO-IR组）和异氟醚组（ISO-S组）。IR组、ISO-IR组建立肺缺血再灌注模型，ISO-IR组吸入1MAC异氟醚30min时行肺缺血再灌注，ISO-S组吸入1MAC异氟醚，不进行肺缺血再灌注。分别在缺血45min、再灌注30、60、120min处死6只大鼠，测定肺组织湿干比（W／D）、髓过氧化物酶（MPO）活性、中性粒细胞（PMN）膜表面CD18和肺组织ICAM-1mRNA表达、支气管肺泡灌洗液（BALF）中自细胞计数、沉渣白细胞分类和总蛋白（TP）浓度，并进行肺组织病理学检查。结果 再灌注期间IR组肺组织W／D、MPO活性、CDl8和ICAM-1mRNA表达、BALF中PMN百分比、TP浓度及PMN膜表面CD18表达均升高。而异氟醚预先给药减弱了缺血再灌注诱导的上述指标的升高。肺组织病理学检查显示异氟醚预先给药减轻了肺缺血再灌注损伤。结论 通过抑制PMN浸润和肺组织ICAM-1mRNA及CD18表达上调，缺血前吸入异氟醚对肺缺血再灌注损伤有一定的保护作用。     

金雀异黄素预先给药对大鼠机械通气所致肺损伤的作用

目的 研究特异性蛋白酪氨酸激酶抑制剂金雀异黄素预先给药对大鼠机械通气所致肺损伤（VILI）的作用。方法 30只健康SD大鼠，随机分为3组，每组10只，A组采用8ml／kg潮气量机械通气；B组采用40ml／kg潮气量机械通气；C组采用40ml／kg潮气量机械通气，并在机械通气前30min腹腔注射金雀异黄素50mg／kg。3组呼吸频率均为80次／min，吸／呼比（I：E）为1：1，PEEP为0，吸人气体为室内空气。机械通气2h后处死大鼠，取肺组织，光镜下观察病理学，测定髓过氧化物酶（MPO）活性、磷酸化p38（p-p38）、p38水平；收集支气管肺泡灌洗液，测定总蛋白、肿瘤坏死因子-α（TNF-α）水平，并进行白细胞（WBC）计数。结果与A组比较，B组支气管肺泡灌洗液总蛋白、WBC计数、TNF-α及肺组织MPO、P—p38／p38水平升高（P〈0．05或0．01），肺组织病理学改变严重；与B组比较，C组上述指标降低（P〈0．01或0．05），肺组织病理学改变明显减轻。结论 金雀异黄素50mg／kg预先给药可减轻大鼠VILI，其机制与抑制了p38通路的激活有关。     

不同剂量6%羟乙基淀粉130/0.4预先给药对大鼠内毒素性急性肺损伤的影响

目的 研究不同剂量6%羟乙基淀粉130/0.4(6% HES 130/0.4)预先给药对大鼠内毒素性急性肺损伤的影响.方法 72只健康清洁级雄性SD大鼠随机分为6组(n=12),对照组(C组)经尾静脉注射生理盐水30 ml/kg;肺损伤组(L组)经尾静脉注射脂多糖(LPS)5 mg/kg;不同剂量6%HES130/0.4组分别经尾静脉注射6%HES 130/0.4 7.5 ml/kg(H1组)、15 ml/kg(H2组)和30 ml/kg(H3组),1 h后再经尾静脉注射LPS 5 mg/kg;H4组经尾静脉注射6%HES 130/0.4 30 ml/kg.各组给药速率均为0.2ml/min.注射LPS后4 h行动脉血气分析,气管插管.每组取6只大鼠,测定肺组织微血管通透性指数(PMPI);每组取6只大鼠,测定支气管肺泡灌洗液(BALF)蛋白浓度、肺组织湿/干重比(W/D)、髓过氧化物酶(MPO)活性,血清肿瘤坏死因子-α(TNF-α)、白细胞介素-1β(IL-1β)、白细胞介素-10(IL-10)、丙二醛(MDA)浓度和超氧化物歧化酶(SOD)活性,观察肺组织病理学.结果 与L组比较,H2组血清TNF-α、IL-1β、MDA浓度和肺组织MPO活性降低,血清IL-10浓度和SOD活性升高,H1组IL-1β浓度降低,H1组、H2组和H3组PMPI、BALF蛋白浓度和W/D均降低(P＜0.05);与H2组比较,H1组和H3组血清TNF-α、MDA浓度和肺组织MPO活性升高,血清SOD活性、IL-10浓度降低,H3组血清IL-1β浓度升高(P＜0.05).H1组、H2组和H3组较L组肺组织损伤较轻,其中H2组损伤最轻.结论 15 ml/kg6%HES 130/0.4预先给药可减轻大鼠内毒素性急性肺损伤,其机制可能与抑制炎性因子释放、减少肺内中性粒细胞聚集和氧自由基生成、改善肺微血管通透性有关.     

虫草多糖预先给药对大鼠内毒素性急性肺损伤的影响

目的 评价虫草多糖预先给药对大鼠内毒素性急性肺损伤的影响.方法 雄性成年SD大鼠40只,体重190～220 g,随机分为5组(n=8):虫草多糖预先给药组(CP1-3,组)采用灌胃法分别给予虫草多糖1、2、3 g/ks,1次/12 h,连续6次,于最后1次给药后2 h时经股静脉注射内毒素5 mg/kg;急性肺损伤组(ALI组)以生理盐水1ml/100 g代替虫草多糖,其余方法同CP组;对照组(C组)以生理盐水1 ml/100 g代替虫草多糖和内毒素,其余方法同CP组.静脉注射内毒索后6 h时处死大鼠,计算肺湿干重比(W/D)、肺渗透指数(PPI);行支气管肺泡灌洗,对支气管肺泡灌洗液(BALF)行白细胞(WBC)和多形核白细胞(PMN)计数;测定肺组织及BALF肿瘤坏死因子α(TNF-α)水平,并行肺组织病理学评分.结果 与C组比较,ALI组和CP1～3组肺W/D、PPI、WBC和PMN计数、肺组织病理学评分、肺组织和BALF TNNF-α水平均升高(P<0.05或0.01);与ALI组比较,CP1组上述指标差异无统计学意义(P>0.05),CP2,3组上述指标降低(P<0.05);与CP2组比较,CP3组PMN计数、肺组织病理学评分、肺组织和BALFTNF-α水平降低(P<0.05).结论 虫草多糖预先给药可减轻大鼠内毒素性急性肺损伤,且呈剂量依赖性,其机制可能与虫草多糖降低肺组织炎性反应有关.     

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。     

促红细胞生成素预先给药对大鼠内毒素性急性肺损伤的影响

目的 探讨促红细胞生成素(EPO)预先给药对大鼠内毒素性急性肺损伤的影响.方法 成年雄性SD大鼠32只,体重180～220 g,随机分为4组(n=8),C组腹腔注射生理盐水4 ml/kg(EPO溶剂对照),30 min后静脉注射生理盐水2 ml/kg[脂多糖(LP3)溶剂对照];EPO组腹腔注射EPO3 000 U/kg,30 min后静脉注射生理盐水2 ml/kg;LPS组腹腔注射生理盐水4 ml/kg,30 min后静脉注射LPS 6 mg/kg;EPO+LPS组腹腔注射EPO 3 000 U/kg,30 min后静脉注射LPS 6 mg/kg.于静脉注射LPS后4 h时处死大鼠,观察肺组织病理学结果 ,计算肺组织湿/干重(W/D)比;测定肺组织髓过氧化物酶(MPO)活性和丙二醛(MDA)、一氧化氮(NO)含量;采用Western blot法测定肺组织诱导型一氧化氮合酶(iNOS)和硝基酪氨酸(NT)的表达.结果 与C组相比,LPS组和EPO+LPs组肺组织W/D比、MPO活性、MDA和NO含量升高,iNOS和NT表达上调(P<0.01);与LPS组相比,EPO+LPS组肺组织W/D比、MPO活性、MDA和NO含量降低,iNOS和NT表达下调(P<0.01).结论 EPO预先给药可减轻大鼠内毒素性急性肺损伤,与其下调iNOS表达,减少NO生成有关.     

阿米洛利预先给药对大鼠内毒素性急性肺损伤的影响

目的 探讨阿米洛利预先给药对大鼠内毒素性急性肺损伤的影响.方法 清洁级雄性SD大鼠32只,体重200～250 g,随机分为4组(n=8):对照组(C组)、急性肺损伤组(ALI组)、阿米洛利组(A组)和阿米洛利预先给药组(AL组).C组股静脉输注生理盐水3 ml,ALI组股静脉输注生理盐水1 ml、内毒素6 mg/kg,A组股静脉输注阿米洛利10 mg/kg、生理盐水2 ml,AL组股静脉输注阿米洛利10 mg/kg、内毒素6 mg/kg,输注速率均为0.05 ml/rain,给药间隔均为30 min.于输注内毒素结束后6 h时处死大鼠取肺,观察肺组织病理学,并行病理学评分,称重后计算肺湿干重比,检测髓过氧化物酶(MPO)活性,测定支气管肺泡灌洗液总蛋白、TNF-α和巨噬细胞炎性蛋白-2(MIP-2)的浓度,采用Western blot法检测肺组织钠氢交换体1(NHE1)、p38丝裂原活化蛋白激酶(p38MAPK)和细胞外信号调节激酶(ERK)的表达水平.结果 与C组比较,ALI组和AL组肺组织病理学评分、肺湿干重比、MPO活性、支气管肺泡灌洗液总蛋白、TNF-α和MIP-2浓度、肺组织NHE1、p38MAPK和ERK的表达水平明显升高(P＜0.01),A组上述指标差异无统计学意义(P＞0.05);与ALI组比较,AL组肺组织病理学评分、肺湿干重比、MPO活性、支气管肺泡灌洗液总蛋白、TNF-α和MIP-2浓度、肺组织NHE1和ERK的表达水平明显降低(P＜0.01),p38MAPK表达差异无统计学意义(P＞0.05).结论 阿米洛利预先给药可减轻大鼠内毒素性急性肺损伤,其机制可能与抑制ERK信号转导通路激活有关.     

Curcumin protects against sepsis-induced acute lung injury in rats

The present study aimed to investigate the effect of curcumin on sepsis-induced acute lung injury (ALI) in rats, and explore its possible mechanisms. Male Sprague-Dawley rats were randomly divided into the following five experimental groups (n = 20 per group): animals undergoing a sham cecal ligature puncture (CLP) (sham group); animals undergoing CLP (control group); or animals undergoing CLP and treated with vehicle (vehicle group), curcumin at 50 mg/kg (low-dose curcumin [L-Cur] group), or curcumin at 200 mg/kg (high-dose curcumin [H-Cur] group).At 6, 12, 24 h after CLP, blood, bronchoalveolar lavage fluid (BALF) and lung tissue were collected. The lung wet/dry weight (W/D) ratio, protein level, and the number of inflammatory cells in the BALF were determined. Optical microscopy was performed to examine the pathologic changes in lungs. Myeloperoxidase (MPO) activity, malondialdehyde (MDA) content, as well as superoxidase dismutase (SOD) activity were measured in lung tissues. The expression of inflammatory cytokines, tumor necrosis factor-alpha (TNF-α), interluekin-8 (IL-8), and macrophage migration inhibitory factor (MIF) were determined in the BALF. Survival rates were recorded at 72 h in the five groups in another experiment. Treatment with curcumin significantly attenuated the CLP-induced pulmonary edema and inflammation, as it significantly decreased lung W/D ratio, protein concentration, and the accumulation of the inflammatory cells in the BALF, as well as pulmonary MPO activity. This was supported by the histopathologic examination, which revealed marked attenuation of CLP-induced ALI in curcumin treated rats. In addition, curcumin significantly increased SOD activity with significant decrease in MDA content in the lung. Also, curcumin caused down-regulation of the inflammatory cytokines TNF-α, IL-8, and MIF levels in the lung. Importantly, curcumin improved the survival rate of rats by 40%-50% with CLP-induced ALI. Taken together, these results demonstrate the protective effects of curcumin against the CLP-induced ALI. This effect can be attributed to curcumin ability to counteract the inflammatory cells infiltration and, hence, ROS generation and regulate cytokine effects.     

内毒素预处理对内毒素血症大鼠肺的作用及机制探讨

目的 观察内毒素预处理对内毒素血症大鼠肺的作用及其机制。方法 将雄性Wistar大鼠84只随机分为7组：生理盐水(NS)组,内毒素脂多糖(LPS)2h、4h、6h组和LPS预处理2h、4h、6h组,每组12只。LPS预处理各组大鼠经腹腔注射LPS0．25mg／kg,24h后再注射LPS0．5mg/kg,NS组和LPS各组在上述时间均给予等容量NS;第2次腹腔注射72h后,LPS各组和LPS预处理各组大鼠经静脉注入(静注)LPS 10mg／kg,NS组注射等量NS。NS组在静注NS后6h,LPS2h、4h、6h组和LPS预处理2h、4h、6h组在静注LPS后2、4、6h时各取6只大鼠取血,行血气分析;取左侧肺组织检测细胞间黏附分子-1(ICAM-1)mRNA及抑制性κB-α(IκB-α)蛋白表达;计数右肺支气管肺泡灌洗液(BALF)中白细胞数,测蛋白含量。上述7组另取6只大鼠,在上述相同时点取全肺,计算肺体指数,测定髓过氧化酶(MPO)。结果 LPS各组大鼠较NS组大鼠肺体指数、BALF中白细胞数和蛋白及肺组织MPO含量均增加,氧分压和HCO3^-下降;而LPS预处理各组大鼠上述各指标变化明显减轻。肺组织ICAM-1 mRNA在LPS2h、4h和6h组表达递增,而在LPS预处理各组表达显著减少;LPS2h组肺组织IκB-α蛋白表达较NS组减少,而LPS预处理2h组较LPS2h组表达增加。结论 内毒素预处理可防止内毒素血症时的肺损伤,可能与内毒素预处理使肺组织IκB-α蛋白生成增加和(或)消耗减少有关。     

七氟烷预处理对脂多糖致大鼠急性肺损伤的保护作用

目的 评价七氟烷预处理对脂多糖(lipopolysaccharide,LPS)所致大鼠急性肺损伤(acute lung injury,ALI)的影响.方法 72只SD大鼠随机分成6组:NS组、LPS组和七氟烷预处理(S-1 h组、S-6 h组、S-12 h组、S-24 h组).通过气管内滴注LPS建立大鼠ALI模型.大鼠在气道内给予LPS或NS后6 h处死,检测不同时间点七氟烷预处理(2.4%,30 min)对支气管肺泡灌洗液(bronchoalveolar lavage fluid,BALF)中白细胞计数、细胞因子TNF-α和IL-1β水平,肺组织髓过氧化物酶(myeloperoxidase,MPO)活性,肺血管通透性及肺组织病理学等的影响.结果 与NS组相比,LPS组肺组织损伤程度,BALF白细胞计数以及TNF-α和IL-1β水平,血管通透性和肺组织MPO活性均显著增高(P<0.01).给予LPS前1 h和24 h七氟烷预处理能降低肺组织MPO活性,BALF中IL-1β水平及白细胞计数(P<0.01),而S-6h组和S-12 h组与IPS组相比无明显差别.七氟烷预处理均能够降低肺血管通透性和BALF中TNF-α水平(P<0.01),且以S-1 h和S-24h组为显著(P<0.01).提示七氟烷预处理对LPS所致肺损伤具有早期和延时的保护作用.结论 气道内给予LPS1 h和24 h前七氟烷预处理对LPS致大鼠ALI具有保护作用.     

Glycyrrhizin treatment is associated with attenuation of lipopolysaccharide-induced acute lung injury by inhibiting cyclooxygenase-2 and inducible nitric oxide synthase expression

Glycyrrhizin (GL), a major active constituent of licorice root, has been attributed numerous pharmacologic effects, including anti-inflammatory, anti-viral, anti-tumor, and hepatoprotective activities. In this study, we investigated the anti-inflammatory effect of GL on lipopolysaccharide (LPS)-induced acute lung injury (ALI) in mice. ALI was induced in Balb/c mice by intratracheal instillation of LPS (1 mg/kg). Before 1 h of LPS administration, the mice received intraperitoneal injection of GL at varied doses (10, 25, and 50 mg/kg). The severity of pulmonary injury was evaluated 12 h after LPS administration. GL pretreatment led to significant attenuation of LPS induced evident lung histopathologic changes, alveolar hemorrhage, and neutrophil infiltration with evidence of reduced myeloperoxidase (MPO) activity. The lung wet/dry weight ratios, as an index of lung edema, were markedly reduced by GL pretreatment. The concentrations of pro-inflammatory cytokines interleukin (IL)-1β and tumor necrosis factor (TNF)-α were elevated in bronchoalveolar lavage fluid (BALF) after LPS administration, which were significantly inhibited by GL pretreatment. GL pretreatment also reduced the concentrations of nitric oxide (NO) in lung tissues. Furthermore, the expression of cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) was suppressed by GL pretreatment. In conclusion, GL potently protected against LPS-induced ALI, and the protective effects of GL may attribute partly to the suppression of COX-2 and iNOS expression.     

c-Jun氨基末端激酶在大鼠内毒素性急性肺损伤中的作用

目的 评价c-Jun氨基末端激酶(JNK)在大鼠内毒素性急性肺损伤中的作用.方法 雄性成年SD大鼠80只,体重250～300 g,采用随机数字表法,将其随机分为4组(n=20):对照组(C组)、急性肺损伤组(ALI组)、SP600125组(S组)和二甲基亚砜组(D组).ALI组、S组和D组尾静脉注射LPS 5 mg/kg,C组尾静脉注射等容量生理盐水;S组和D组给予LPS后,分别尾静脉注射JNK抑制剂SP600125 30 mg/kg或二甲基亚砜0.2 ml.于给予LPS后4 h时,各组处死10只大鼠,回收支气管肺泡灌洗液(BALF)并取肺组织,采用ELISA法检测BALF中TNF-α和IL-1β的浓度,计算肺组织湿重/干重比(W/D比),观察肺组织病理学结果,并进行肺损伤评分.各组其余10只大鼠观察至给予LPS后48 h,记录大鼠生存情况.结果 与C组比较,其余各组BALF中TNF-α和IL-1β的浓度、肺组织W/D比和肺损伤评分升高,生存率降低(P<0.05或0.01);与ALI组比较,S组BALF中TNF-α和IL-1度、肺组织W/D比和肺损伤评分降低,生存率升高(P<0.01),D组差异无统计学意义(P>0.05).结论 JNK的活化参与了大鼠内毒素性急性肺损伤的发生发展.

Abstract：

Objective To evaluate the role of c-Jun N-terminal kinase (JNK) in lipopolysaccharide (LPS)-induced acute lung injury ( ALI) in rats.Methods Eighty male SD rats weighing 250-300 g were randomly divided into 4 groups ( n = 20 each) : control group (group C) ; ALI group; LPS + SP600125 (JNK inhibitor)group (group S) and LPS+ DMSO (the solvent) group (group DMSO) . ALI was induced by intravenous LPS 5mg/kg. In S and DMSO groups, SP600125 30 mg/kg and DMSO 0.2 ml were injected intravenously after LPS administration respectively. Ten animals were sacrificed by exsanguinafions at 4 h after LPS administration in each group. The broncho-alveolar lavage fluid (BALF) was colleted. The TNF-α and IL-1β concentrations in BALF were measured. The lungs were removed for microscopic examination and determination of W/D lung weight ratio. The other 10 animals in each group were observed for 48 h survival rate. Results Intravenous LPS significantly increased TNF-α and IL-1β concentrations in BALF and W/D lung weight ratio, decreased 48 h survival rate and induced histologic damage. Intravenous SP600125 30 mg/kg significantly attenuated the above-mentioned LPS-induced changes. Conclusion Activation of JNK is involved in the development of endotoxin-induced ALI in rats.     

The protective effects of early treatment with propofol on endotoxin-induced acute lung injury in rats

To investigate the effects of treatment with propofol administration at different time point in acute lung injury of endotoxin-induced shock rats. METHODS: 76 male wistar rats were randomly assigned to five groups: A) control group; B) endotoxemic group, receiving intravenous lipopolysaccharide (LPS) 8 mg.kg-1; C) pretreatment group, treated identically to endotoxemic group with the additional administration of propofol (5 mg.kg-1 bolus, followed by infusion at 10 mg.kg-1.h-1) of 1 hr prior to the injection of LPS; D) simultaneously treatment group, treated identically to endotoxemic group with the additional administration of propofol simultaneously with the injection of LPS; E) post-treatment group, which was treated identically to endotoxemic group except for administration of propofol 1 hr after the injection of LPS. PaO2, pH, MAP and survival rate were recorded and plasma NO, TNF-alpha were measured during 5-hr after the injection of LPS. After the rats were killed, lung tissue was sampled to measured expression of inducible nitric oxide synthase (iNOS), nitrotyrosine (NT), myeloperoxidase (MPO) activity, malondialdehyde (MDA), wet-to-dry lung weight ratio (W/D), and pulmonary permeability index (PPI). RESULTS: Compared with the endotoxemic group, both the pretreatment and simultaneously treatment groups, significantly improved PaO2, pH, MAP and 5th hour survival rate of rats, and attenuated endotoxin-induced increased iNOSmRNA, NT expression, MPO activity and MDA level in lung tissue, and decreased pulmonary microvascular permeability, TNF-alpha, NO in plasma. But these beneficial efficacies were blunted in the post-treatment group. CONCLUSIONS: These findings showed that propofol administration may provide protective effects on acute lung injury in endotoxin-induced shock.