抗巨噬细胞移动抑制因子抗体在油酸致急性肺损伤发病中的干预作用

目的:探讨抗巨噬细胞移动抑制因子单克隆抗体(anti-MIFMAb)在油酸诱导的大鼠急性肺损伤(ALI)中的干预作用,及其对巨噬细胞移动抑制因子(MIF)和细胞间粘附分子-1(ICAM-1)表达的影响。方法:雄性Wistar大鼠静脉注射油酸复制ALI为油酸组,静脉注射生理盐水为对照组,大鼠先给予抗-MIF单抗腹腔注射后再给予油酸静脉注射为抗-MIF单抗干预组。静注后4h,3组大鼠分别测定动脉血氧分压(PaO₂),肺泡通透指数等肺损伤指标;用ELISA法测定支气管肺泡灌洗液(BALF)中可溶性细胞间粘附分子-1(sICAM-1)水平;用原位杂交检测MIF和ICAM-1mRNA表达水平;用免疫组化双重套染方法检测巨噬细胞浸润程度与MIF表达的关系。结果:油酸组PaO₂低于对照组和干预组,肺通透性指数高于对照组和干预组(P<0.01),BALF中sICAM-1水平显著高于对照组和干预组(P<0.01)。油酸组肺组织MIF和ICAM-1表达明显高于对照组和干预组(P<0.01),经抗-MIF单抗干预ICAM-1表达变化不明显,但MIF表达显著下调,巨噬细胞浸润减少且肺损伤指标改善。结论:MIF和ICAM-1在介导巨噬细胞对组织的粘附、浸润和ALI的发生发展中起重要作用,抗-MIF单抗主要通过阻断MIF表达,减少巨噬细胞浸润而起肺保护作用。     

肠系膜淋巴管结扎对大鼠急性肺损伤的影响

目的：探讨结扎肠系膜淋巴管对失血-脂多糖（LPS）致大鼠急性肺损伤（ALI）的拮抗作用。方法：雄性Wistar大鼠45只，均分为结扎组、未结扎组、假手术组，以失血、LPS复制二次打击模型，结扎组行肠系膜淋巴管结扎术致肠淋巴液断流。在手术创伤后24 h，所有大鼠颈总动脉放血，进行血气分析；从左肺收集支气管肺泡灌洗液（BALF），观察WBC、NO及其合酶、SOD、MDA以及肺泡通透性指数等指标的水平；右肺制备10%组织匀浆，检测MPO、ATPase活性等指标；观察右肺后叶超微结构。结果：二次打击后，未结扎组动脉血PaCO2、BALF中细胞总数及PMN、NO2-/NO3-、NOS、MDA含量以及肺匀浆MPO活性、肺通透性指数均显著高于假手术组，动脉血pH、PaO2、BALF中SOD、肺匀浆ATPase活性显著低于假手术组（P<0.01，P<0.05）；结扎组大鼠BALF中细胞总数及PMN、MDA、NO2-/NO3-含量、肺通透性指数均显著高于假手术组，BALF中SOD活性显著低于假手术组（P<0.01，P<0.05）。但结扎组大鼠动脉血pH、PaO2、肺匀浆ATPase活性显著高于未结扎组，动脉血PaCO2、BALF中细胞总数及PMN、NO2-/NO3-、NOS、MDA含量、肺通透性指数及肺匀浆MPO显著低于未结扎组（P<0.01，P<0.05）；且肺血管内皮细胞损伤程度较未结扎组轻微。结论：肠系膜淋巴管结扎可减轻失血-LPS致大鼠的急性肺损伤。提示二次打击的肠系膜淋巴液在大鼠急性肺损伤的发病过程中发挥着重要作用。     

巨噬细胞浸润及细胞间粘附分子-1表达在油酸致大鼠急性肺损伤发病中的作用

目的:探讨巨噬细胞浸润及细胞间粘附分子-1(ICAM-1)表达在油酸诱导的大鼠急性肺损伤(ALI)中的作用。方法:雄性Wistar大鼠静脉注射油酸复制ALI为油酸组,静脉注射生理盐水为对照组。静注后4h,测定血气(左心PaO₂)、肺泡通透指数等肺损伤指标。支气管肺泡灌洗液(BALF)中巨噬细胞比和可溶性细胞间粘附分子-1(sICAM-1)水平。用原位杂交检测ICAM-1mRNA表达水平和免疫组化双重套染方法检测巨噬细胞浸润程度与ICAM-1表达的关系。结果:油酸组PaO₂低于对照组、肺泡通透性指数高于对照组(P＜0.01),BALF中巨噬细胞比例,sICAM-1水平显著高于对照组(P＜0.01)。油酸组肺组织ICAM-1表达明显高于对照组,且肺组织中巨噬细胞浸润数、ICAM-1表达水平和肺损伤指标呈显著正相关。结论:巨噬细胞浸润在油酸致急性肺损伤中起重要作用,ICAM-1参与介导了巨噬细胞对组织的粘附、浸润和ALI的发生发展。     

氯沙坦抑制急性肺损伤大鼠肺组织LOX-1表达

 目的 研究氯沙坦干预大鼠急性肺损伤模型肺组织血凝素样氧化低密度血浆脂蛋白受体-1（LOX-1）表达的变化,探讨LOX-1在急性肺损伤中的表现及氯沙坦的干预机制。方法 将大鼠随机分成：对照组、脂多糖(LPS)组（5mg/kg）及氯沙坦治疗组（8mg/kg）,每组10只。检测动脉血氧分压（PaO2）、肺湿/干质量值（W/D）、支气管肺泡灌洗液(BALF)蛋白含量、血浆和BALF中TNF-α水平及肺组织病理变化,比色法测定肺组织髓过氧化物酶（MPO）活性,用RT-PCR法检测肺组织LOX-1 mRNA水平,western blot法检测肺组织中LOX-1、ICAM-1、Cleaved caspase-3蛋白的表达。结果 脂多糖处理后大鼠肺部炎症反应显著,PaO2较对照组下降,而肺W/D值、BALF蛋白含量及TNF-α水平、血浆TNF-α水平、MPO活性升高（P<0.05）;LOX-1 mRNA和LOX-1、ICAM-1及Cleaved caspase-3蛋白表达升高（P<0.05）。氯沙坦显著缓解上述变化（P<0.05）。结论 氯沙坦可能通过抑制LOX-1介导的炎症及细胞凋亡减轻急性肺损伤。     

联合应用氨溴索与小剂量肝素对急性肺损伤ICAM-1和EP-selectin的影响

目的: 制作急性肺损伤(ALI)模型并检测细胞间黏附分子-1(ICAM-1)、E-选择素和P-选择素在实验兔血清、肺组织及支气管肺泡灌洗液(BALF)中的变化情况以探讨三者在ALI中的作用并观察联合应用氨溴索与小剂量肝素对其的影响。方法: 24只健康兔随机分成3组:对照组(NC组),油酸损伤组(OA组),氨溴索＋小剂量肝素治疗组(AH组)。采用耳缘静脉法静注油酸复制兔ALI模型,检测各组动脉氧分压(PaO₂),ELISA法检测ICAM-1和E-选择素,TUNEL法检测凋亡指数(AI),免疫组化检测P-选择素,电镜观察肺组织超微结构变化并测定湿干重比值(W/D)。结果: 与NC组比较, OA组和AH组PaO₂显著降低(P<0.01),但AH组显著高于OA组(P<0.01); ICAM-1、E-选择素的浓度(血清、肺组织及BALF中)、肺组织AI和W/D升高(P<0.05或P<0.01),但AH组低于OA组(P<0.05或P<0.01)。与同组给予治疗药物前0 h比较,NC组无差异(P>0.05),OA组各时点PaO₂显著降低(P<0.01),ICAM-1和E-选择素浓度显著升高(P<0.01),AH组各时点PaO₂降低(P<0.05)、ICAM-1和E-选择素浓度升高(P<0.05)。肺组织中P-选择素在OA组表达较为广泛:主要为炎症细胞、毛细血管的内皮细胞和血管内的血浆等,NC组呈低水平表达,AH组的表达介于两者之间。细胞凋亡以OA组最为明显,NC组未见细胞凋亡或偶有凋亡,AH组凋亡的细胞明显比OA组减少。结论: 在OA致ALI时,ICAM-1、E-选择素和P-选择素明显增高,参与了ALI的发生、发展;联合应用氨溴索与小剂量肝素可以降低ICAM-1、E-选择素和P-选择素的水平,减轻肺脏细胞的损伤、改善肺通气和换气功能、减轻肺水肿,从而发挥对ALI的防治作用。     

NF-κB在大鼠急性肺损伤模型肺组织中的表达及N-乙酰半胱氨酸的影响

目的 :检测NF κB在LPS诱导的急性肺损伤 (ALI)肺组织中的表达 ,以及N 乙酰半胱氨酸 (NAC)对ALI的抑制作用。方法 :采用免疫组化染色 (ABC法 )和Westernblot,检测NF κB在急性肺损伤大鼠气道和肺组织中的表达 ,以及NAC干预后活性NF κB表达的变化。结果 :正常对照组大鼠气道黏膜上皮和肺间质中 ,仅见少量散在的NF κB核阳性细胞 ;而LPS诱导ALI后 ,气道黏膜、肺间质、肺泡腔及血管内皮细胞中NF κB核阳性的细胞明显增多 (P <0 .0 1)。NF κB核阳性反应细胞主要为气道黏膜上皮细胞、浸润的炎症细胞、肺泡上皮细胞和血管内皮细胞。NAC治疗组NF κB核阳性细胞较LPS诱导的ALI组及对照组均明显减少 (P <0 .0 1)。Westernblot的结果显示 ,LPS诱导的ALI后不同时间点 ,NF κB的表达不同 ,于急性肺损伤 3h达高峰。各时间点NF κB的表达均较正常对照组高。结论 :LPS诱发的大鼠急性肺损伤的气道和肺组织内NF κB的表达增加 ,肺组织内的多数细胞参与了NF κB的激活。NAC可通过抑制NF κB的激活减轻急性肺损伤的炎症程度     

Treatment of Low Molecular Weight Heparin Inhibits Systemic Inflammation and Prevents Endotoxin-Induced Acute Lung Injury in Rats

To determine whether low molecular weight heparin (LMWH) is able to reduce pulmonary inflammation and improve the survival in rats with endotoxin-induced acute lung injury (ALI). Rat ALI model was reproduced by injection of lipopolysaccharide (LPS) into tail vein. Rats were divided randomly into three groups: control group, ALI group, LMWH-treated group. Blood was collected and lung tissue was harvested at the designated time points for analysis. The lung specimens were harvested for morphological studies, streptavidin-peroxidase immunohistochemistry examination. Lung tissue edema was evaluated by tissue water content. The levels of lung tissue myeloperoxidase (MPO) were determined. Meanwhile, the nuclear factor-kappa B (NF-κB) activation, tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β) levels and high mobility group box 1 (HMGB1) and intercellular adhesion molecule-1 (ICAM-1) protein levels in the lung were studied. In survival studies, a separate group of rats were treated with LMWH or sterile saline after LPS administration. Then, the mortality was recorded. Treatment with LMWH after ALI was associated with a reduction in the severity of LPS-induced lung injury. Treatment with LMWH significantly decreased the expression of TNF-α, IL-1β, HMGB1 and ICAM-1 in the lung of ALI rats. Similarly, treatment with LMWH dramatically diminished LPS-induced neutrophil sequestration and markedly reduced the enhanced lung permeability. In the present study, LMWH administration inhibited the nuclear translocation of NF-κB in the lung. Survival was significantly higher among the LMWH-treated group compared with the ALI group. These data suggest that LMWH attenuates inflammation and prevents lethality in endotoxemic rats.     

p38 MAPK-HSP27信号通路在内毒素致大鼠肺损伤中的作用

 目的：观察p38丝裂原激活蛋白激酶（p38 MAPK)-热休克蛋白27（HSP27）信号通路在急性肺损伤病理过程中的变化规律。方法：健康雄性Wistar大鼠（300~320 g）随机分成正常对照组（A组）、急性肺损伤组（B组）及急性肺损伤+SB203580组（C组）。通过腹腔注射内毒素建立急性肺损伤大鼠模型,分别于实验开始后的0、2、4、6、8 h处死各组大鼠。检测支气管肺泡灌洗液（BALF）白细胞介素6（IL-6）、肿瘤坏死因子α（TNF-α）及BALF中蛋白含量。苏木素-伊红（HE）染色检查肺组织病理变化及免疫荧光方法检测内皮细胞内F-actin和G-actin,计算肺湿干重比值（W/D）。检测肺组织中磷酸化p38 MAPK（p-p38 MAPK）及磷酸化HSP27（p-HSP27）的含量。 结果：B组在实验后2 h BALF中蛋白水平和肺W/D开始明显增加,给予内毒素后8 h肺泡上皮肿胀,肺泡壁增宽,肺泡间质和肺泡腔水肿明显,肺泡内炎症细胞、红细胞和蛋白渗出明显增多,表现出急性肺损伤的病理改变。在给予了p38 MAPK抑制剂SB203580后的C组BALF中蛋白水平及肺W/D分别比B组明显减少,肺泡内炎症细胞、红细胞和蛋白渗出、间质与肺泡水肿均较B组减轻。B组均在实验后2 h血清及BALF中TNF-α和IL-6的浓度开始增加,p-p38 MAPK及p-HSP27的肺内表达开始增加,与A组相比有显著差异。B组实验后8 h的F-actin的表达明显比A组实验后0 h及8 h的增加,给予p38 MAPK抑制剂SB203580的C组肺p-HSP27 和F-actin的表达分别比B组明显减少。结论：内毒素可以通过激活p38 MAPK-HSP27信号通路引起急性肺损伤;阻断该信号通路可以减轻肺损伤。     

中性粒细胞胞外诱捕网在新生大鼠急性肺损伤中的作用

目的:探讨中性粒细胞胞外诱捕网(NETs)在新生大鼠急性肺损伤(ALI)中的作用。方法:取出生7 d的SD大鼠30只,按照随机数字表法分成生理盐水对照组、ALI组及ALI+脱氧核糖核酸酶(Dnase)组,每组10只。ALI组用脂多糖(LPS)以20 mg/kg的剂量腹腔注射,ALI+Dnase组则在注射LPS后即腹腔注射Dnase(5 mg/kg)。给药6 h后,水合氯醛麻醉大鼠,收集支气管肺泡灌洗液(BALF),荧光酶标仪检测BALF中游离DNA(cf-DNA)的含量;右肺组织固定于4%多聚甲醛中,HE染色观察各组大鼠肺组织形态结构;左肺组织制备肺组织匀浆,酶联免疫吸附测定(ELISA)法检测肺组织匀浆中白细胞介素6(IL-6)及肿瘤坏死因子α(TNF-α)的含量;使用免疫荧光法与Western blot检测各组大鼠肺组织中瓜氨酸化组蛋白H3(CitH3)及髓过氧化物酶(MPO)的生成情况。结果:与对照组相比,ALI组与ALI+Dnase组中cf-DNA、CitH3、MPO、IL-6及TNF-α水平均升高(P<0.05),肺组织中炎性细胞浸润严重;与ALI组相比,ALI+Dnase组新生大鼠肺组织中cf-DNA、Cith3、MPO、IL-6及TNF-α水平降低(P<0.05),ALI+Dnase组炎症浸润程度降低。结论:新生大鼠ALI中,NETs水平为反映肺组织损伤的重要指标,NETs可能为治疗新生儿ALI的新靶点。     

胆红素对抗脂多糖诱导致大鼠急性肺损伤的实验研究

目的：探讨胆红素对抗急性肺损伤（ALI）的作用及其机制。方法： 用雄性Wistar大鼠（200-250 g） 30只，随机分为生理盐水对照组、脂多糖（LPS）致ALI动物模型组、胆红素干预组。观察病理形态变化并检测肺组织肺系数（LI）；支气管肺泡灌洗液（BALF）中白细胞（WBC）计数、中性粒细胞（PMN）百分比、蛋白质含量（Pr）；肺泡通透指数（LPI）及肺组织匀浆中超氧化物歧化酶（SOD）、脂质过氧化产物丙二醛（MDA）、谷胱甘肽过氧化物酶（GSH-Px）水平变化。结果： （1）ALI模型组LI，BALF中WBC计数、PMN百分比、Pr及LPI均显著高于生理盐水对照组（均P<0.01）。胆红素干预组LI，BALF中WBC计数和LPI均显著低于AIL模型组（均P<0.01），PMN百分比和Pr明显低于ALI模型组（均P<0.05），且与生理盐水对照组无显著差异（P>0.05）。（2）ALI模型组MDA含量显著多于生理盐水对照组（P<0.01），SOD活性和GSH-Px含量都明显低于生理盐水对照组(P<0.01)。胆红素干预组MDA含量明显低于ALI模型组 (P<0.01)，而SOD活性和GSH-Px含量显著多于ALI模型组（P<0.01，P<0.05)且与生理盐水对照组无显著差异（P>0.05）。结论： 胆红素通过其抗氧化作用对抗大鼠急性肺损伤。     

Effects of HMGB1 on PMN apoptosis during LPS-induced acute lung injury

Objective

To observe the effects of intravenous injection of HMGB1 inhibitor sodium butyrate on changes in apoptosis of PMN during LPS-induced acute lung injury in rats and HMGB1 in vitro on human circulating PMN apoptosis, in order to clarify the role of HMGB1 in the pathogenesis of acute lung injury.

Methods

(1) LPS-induced acute lung injury rat model was developed by LPS infusion. At different time-points after LPS challenge in the presence or absence of sodium butyrate (SB), the rat tissue sample, peripheral blood PMNs and BALF were collected. RT-PCR was applied to examining rat lung tissue HMGB1 mRNA expression level, and Western blotting analysis was adopted to determine expression of rat lung tissue HMGB1 protein. PMN apoptotic changes were determined by flow cytometric (FCM) analysis, Giemsa staining and TdT-mediated dUTP nick end labeling (TUNEL) method. (2) Separated and purified human circulating PMN were coincubated for 24 h with different doses of HMGB1 (0, 10, 100, 1000 ng/ml, respectively) at 37 °C in 5% CO₂. PMN apoptosis rate was determined by flow cytometric (FCM) analysis and by TdT-mediated dUTP nick end labeling (TUNEL) method.

Results

(1) The percentage of apoptosis of PMN in rat model of LPS-induced ALI was gradually decreased as compared with that of normal control. The PMN apoptosis-initiation time and non-survival time in rat BALF prolonged significantly as compared with that of normal control. The injured rat lung tissue HMGB1 mRNA and protein expression was upregulated 6–24 h after LPS exposure; SB intervention significantly ameliorated the upregulation. In addition, the morphologic examination indicated that the edema severity and pathological changes of lung tissues were excessively aggravated in rats after LPS administration. By comparison, SB treatment diminished the severity of lung damage. Combined with lung HMGB1 expression level, the above changes indicate that the pathological changes of lung tissue were related to the injured lung HMGB1 expression, as well as apoptotic changes in PMN. (2) After coincubation of HMGB1 with human circulating PMNs, TUNEL and flow cytometry were performed. The study revealed that PMN apoptosis ratios was (40.53 ± 4.12) % in control group (PMNs + RPMI 1640 medium), (19.05 ± 2.44) % in LPS group (PMNs + RPMI 1640 medium + 10 μg/ml LPS), (40.52 ± 2.73) % in HMGB1-1 group (PMNs + RPMI 1640 medium + 10 ng/ml HMGB1), (34.89 ± 1.15) % in HMGB1-2 group (PMNs + RPMI 1640 medium + 100 ng/ml HMGB1), and (18.77 ± 3.02) % in HMGB1-3 group (PMNs + RPMI 1640 medium + 1 000 ng/ml HMGB1). There was statistical significance. Meanwhile, PMN TUNEL positive rate was (31.42 ± 4.40) %, (31.39 ± 3.80) %, (25.62 ± 2.46) %, and (17.98 ± 3.20) % in control group, HMGB1-1 group, HMGB1-2 group and HMGB1-3 group, respectively. The inhibitory effect was HMGB1 dose-depended as compared with that of control group.

Conclusion

After LPS challenge, high expression of rats' lung HMGB1 mRNA occurs at a later phase, but keeps for a long time. Sodium butyrate (SB) treatment attenuated LPS-induced PMN apoptosis delay and inhibition, and down-regulated HMGB1 mRNA expression of injured lung. HMGB1 in vitro inhibited human circulating PMN apoptosis markedly, and the inhibitory effect was HMGB1 dose-depended. The results demonstrated that HMGB1 may play an important role as a modulator in apoptotic changes in PMN during LPS-induced ALI. It concludes that HMGB1 may contribute to the development of PMN apoptotic changes during LPS-induced acute lung injury.     

长春西汀注射液减轻脂多糖诱导的大鼠急性肺损伤

目的:观察长春西汀注射液对脂多糖(lipopolysaccharide,LPS)诱导大鼠急性肺损伤(acute lung injury,ALI)的作用,并研究初步的作用机制。方法:雄性Wistar大鼠50只,随机分为正常对照组(control)、模型组(ALI组)以及长春西汀低剂量组、中剂量组和高剂量组,每组10只。正常对照组股静脉注射0.9%氯化钠注射液(5 m L/kg);模型组股静脉注射LPS 10 mg/kg;长春西汀低、中和高剂量组股静脉注射LPS 10 mg/kg,30 min后分别腹腔注射长春西汀注射液0.2 mg/kg、0.7 mg/kg和1.2 mg/kg。伊红染色观察肺部组织病理学切片,TUNEL法检测肺组织的细胞凋亡,分光光度法检测并计算肺组织髓过氧化物酶(MPO)活性,Western blot法检测肺组织中NF-κB、ICAM-1、VCAM-1、Bax与Bcl-2的蛋白水平。结果:与模型组相比,采用长春西汀给药后,明显减轻急性肺损伤的肺组织结构损伤与炎性细胞浸润,降低肺组织凋亡的细胞数与MPO活性,下调细胞中NF-κB、ICAM-1、VCAM-1与Bax的蛋白表达水平,上调Bcl-2的蛋白表达水平。结论:长春西汀注射液对急性肺损伤大鼠的肺组织具有保护作用,可能与降低肺组织中MPO活性,以及调控NF-κB、ICAM-1、VCAM-1、Bax与Bcl-2蛋白表达水平有关。     

腺苷A2A受体激动剂CGS21680对脂多糖诱导的小鼠急性肺损伤的保护作用

 目的：探讨腺苷A2A受体激动剂对脂多糖(LPS)诱导的急性肺损伤（ALI）小鼠的作用。方法：采用LPS（10 mg/kg）气管内注射6 h后的ALI小鼠模型。实验动物随机分为生理盐水对照组、ALI组、CGS21680治疗组和CGS21680对照组。测定各组6 h后肺湿重/干重比值（W/D）。比色法测定各组肺组织中髓过氧化物酶(MPO)活性。Western blotting分析各组肺组织中细胞间黏附分子1（ICAM-1）和血管细胞黏附分子1（VCAM-1）的表达。酶联免疫吸附法（ELISA）检测各组小鼠血清中单核细胞趋化蛋白1（MCP-1）的浓度。观察各组肺组织病理改变。结果：ALI组肺W/D、MPO活性、ICAM-1及VCAM-1表达和MCP-1浓度均较对照组显著升高。CGS21680治疗组前述各项指标较ALI组有显著下降。CGS21680组较对照组各项指标无显著差异。肺组织病理显示,ALI组可见肺间质明显充血水肿,大量炎症细胞浸润,部分肺泡腔内可见红细胞。CGS21680治疗组可显著改善肺组织的病理变化。结论：腺苷A2A受体激动剂CGS21680可明显减轻LPS诱导的ALI小鼠肺组织的炎症反应及肺组织水肿,提示腺苷A2A受体激动剂在急性肺损伤中具有保护作用。     

藤黄酸减轻脂多糖诱导的小鼠急性肺损伤

目的探讨藤黄酸(GA)对脂多糖(LPS)所致小鼠急性肺损伤的保护作用及其机制。方法采用尾静脉注射LPS(4 mg/kg)建立小鼠急性肺损伤模型。实验将小鼠随机分为对照组(control组)、模型组(model组)、藤黄酸组(GA组)和藤黄酸预处理组(GA+LPS组),6 h后测定肺湿/干重比值(W/D);检测髓过氧化物酶(MPO)活性;检测肺泡灌洗液(BALF)中蛋白含量和白细胞计数;ELISA检测肺匀浆中白介素-1β(IL-1β)和肿瘤坏死因子-α(TNF-α)含量。结果模型组小鼠肺W/D、MPO活性、BALF中蛋白含量和白细胞数量均增加,肺组织IL-1β和TNF-α水平升高(均P0.01);藤黄酸预处理可减轻LPS引起的以上指标变化(均P0.05)。结论 GA可减轻LPS诱导的急性肺损伤,其机制可能与降低肺组织IL-1β和TNF-α的含量、抑制中性粒细胞在肺部的聚集和减轻肺部水肿相关。     

实验性急性肺损伤肺组织中细胞间粘附分子的表达及大黄对其影响

目的:主要探讨肺组织中细胞间粘附分子-1(ICAM-1mRNA)表达与急性肺损伤(ALI)的关系和大黄对其影响。方法:注射脂多糖(LPS)复制ALI动物模型并分为LPS组、对照组、大黄+LPS组、地塞米松+LPS组。观察病理形态和ALI生物学标志并测定肺组织中ICAM-1mRNA的表达。结果:肺血管内皮细胞ICAM-1mRNA表达在LPS组显著高于对照组(P＜0.01),而大黄+LPS和地塞米松+LPS组显著弱于LPS组(P＜0.05,P＜0.01)。肺湿/干重比,肺泡灌洗液中性粒细胞比、蛋白含量以及肺血管壁通透性、肺泡通透指数也显著小于LPS组。结论:在ALI肺组织中ICAM-1mRNA表达增强参与了ALI发病的作用,大黄可使ICAM-1mRNA的表达减弱从而使肺组织损伤减轻。     

Role of transcriptional factor Nrf2 in the acute lung injury of mice

Objective: This study aimed to investigate the expression and role of Nrf2 in the acute lung injury (ALI) of mice. Methods: A total of 60 BABL/c mice were randomly divided into 2 groups: ALI group and control group. In ALI group, ALI was introduced by injection of LPS. Immunohistochemistry was performed to detect Nrf2 expression in the lung; Western blot assay was employed to detect the expression of Nrf2 in the lung homogenate; ELISA was conducted to detect the expression of Nrf2 in the lung homogenate and BALF. Results: As compared to control group, ALI mice had a high Nrf2 expression in the lung as shown in immunohistochemistry, and the Nrf2 expression in the lung homogenate and BALF also increased markedly (P<0.05). Conclusion: The Nrf2 expression increases in the lung and BALF of ALI mice, suggesting that Nrf2 is involved in the inflammation during ALI and may serve as a new target in the therapy of ALI.     

Propofol Protects Rats and Human Alveolar Epithelial Cells Against Lipopolysaccharide-Induced Acute Lung Injury via Inhibiting HMGB1 Expression

High-mobility group box 1 (HMGB1) plays a key role in the development of acute lung injury (ALI). Propofol, a general anesthetic with anti-inflammatory properties, has been suggested to be able to modulate lipopolysaccharide (LPS)-induced ALI. In this study, we investigated the effects of propofol on the expression of HMGB1 in a rat model of LPS-induced ALI. Rats underwent intraperitoneal injection of LPS to mimic sepsis-induced ALI. Propofol bolus (1, 5, or 10 mg/kg) was infused continuously 30 min after LPS administration, followed by infusion at 5 mg/(kg?·?h) through the left femoral vein cannula. LPS increased wet to dry weight ratio and myeloperoxidase activity in lung tissues and caused the elevation of total protein and cells, neutrophils, macrophages, and neutrophils in bronchoalveolar lavage fluid (BALF). Moreover, HMGB1 and other cytokine levels were increased in BALF and lung tissues and pathological changes of lung tissues were excessively aggravated in rats after LPS administration. Propofol inhibited all the above effects. It also inhibited LPS-induced toll-like receptor (TLR)2/4 protein upexpression and NF-κB activation in lung tissues and human alveolar epithelial cells. Propofol protects rats and human alveolar epithelial cells against HMGB1 expression in a rat model of LPS-induced ALI. These effects may partially result from reductions in TLR2/4 and NF-κB activation.     

急性肺损伤大鼠多形核白细胞L选择素表达的变化及其意义

目的:探讨急性肺损伤(ALI)大鼠循环血多形核白细胞(PMN)表面L选择素(L-selectin)表达的变化及其在ALI发病中的作用。方法:静注内毒素(ET)复制大鼠ALI模型,循环血PMNL选择素表达用免疫荧光间接法及流式细胞仪进行检测。结果:L选择素荧光信号集中分布于PMN细胞膜表面,对照组PMNL选择素表达最强;ET致伤后5min大鼠PMN表面L选择素表达明显低于对照组(P＜0.05),ET致伤后15-30minL选择素表达最低(P＜0.01),伤后60min时PMN表面L选择素表达仍明显低于对照组(P＜0.01)。结论:正常状态下L选择素在PMN表面呈结构性表达,ET致伤后PMN表面的L选择素蛋白表达迅速减少,伤后15min时最低。L选择素可能在ALI的发生发展过程中起一定的作用。     

P38 MAPK抑制剂对急性肺损伤大鼠细胞间黏附分子-1表达的影响

目的观察P38 MAPK抑制剂预处理对脂多糖(LPS)致大鼠急性肺损伤(ALI)细胞间黏附分子-1(ICAM-1)的影响,探讨P38 MAPK抑制剂干预ALI的理论基础。方法腹腔内注射 气管内给LPS复制大鼠ALI模型,用免疫组化方法测定肺组织ICAM-1的表达。结果模型组和预处理组的ICAM-1表达显著高于对照组(P<0.01,P<0.05),且模型组高于预处理组(P<0.05)。结论P38MAPK抑制剂预处理可下调大鼠细胞黏附分子ICAM-1的表达,减轻肺组织的病理损害,能起到防治ALI的作用。