Histopathological observation of rabbits lung tissue after bronchoalveolar lavage

目的 观察支气管肺泡灌洗后兔肺组织病理变化.方法 将实验用新西兰兔31只予以气管插管并分为生理盐水10 ml(A组,n=11)、亚胺培南(50 mg/10 ml) (B组,n=8)和氟康唑(800 μg/10 ml) (C组,n=12)3组.灌洗2h后处死动物,采用常规石蜡组织切片和HE染色法对兔肺组织进行病理观察.结果 肺细支气管腔和部分肺泡腔内可见淡红色液体,并由此导致局限性肺气肿和/或肺不张.肺细支气管管腔内和管壁积有散在的中性粒细胞;支气管黏膜上皮坏死、剥脱.3组上述病变组间无明显差异.结论 与生理盐水灌洗比较,亚胺培南或氟康唑局部肺泡灌洗并未增加局部病理损伤.     

支气管肺泡灌洗对兔肺泡内TNF-α的影响

目的 观察生理盐水、亚胺培南、氟康唑支气管肺泡灌洗后对兔肺泡内炎症因子的影响.方法 新西兰白兔34只气管插管后分为四组:A组(3只)作为空白对照;B组(11只)用生理盐水支气管肺泡灌洗;C组(8只)用亚胺培南灌洗;D组(12只)用氟康唑灌洗.2 h后处死动物,ELISA法比较肺泡灌洗液及肺组织匀浆中肿瘤坏死因子α(TNF-α)含量.结果 四组肺泡灌洗液的TNF-α水平各组间差异无统计学意义(P>0.05).C组肺组织匀浆TNF-α水平低于A、B、D组(P<0.05).结论 生理盐水、亚胺培南、氟康唑支气管肺泡灌洗并未增加局部TNF-α的释放.     

急性肺损伤大鼠体内明胶酶的活性变化及大豆胰蛋白酶抑制剂的干预效应

目的探讨急性肺损伤大鼠体内基质金属蛋白酶2,9(MMP-2,MMP-9)活性的变化以及大豆胰蛋白酶抑制剂(soybean trypsin protease inhibitor,SBTI)的干预效应。方法90只SD大鼠随机分为假手术组(Sham组,n=30)、内毒素组(LPS组,n=30)、大豆胰蛋白酶抑制剂组(SBTI组,n=30)。向LPS和STBI组大鼠气管内一次性注入0.3ml含LPS(6mg.kg-1)的生理盐水复制ALI模型,假手术组大鼠则在气管内一次性注入等量生理盐水。SBTI组于造模前1天腹腔注射给予100mg.kg-1.d-1SBTI(溶于0.5ml生理盐水),假手术组和LPS组大鼠腹腔注射等量的生理盐水,3组动物同步于气管内LPS灌注后d1、d3、d7分别随机处死10只。收集肺泡灌洗液,冰浴匀浆肺组织制备匀浆液,-80℃冻存。Bradford法测定血浆蛋白含量和肺泡灌洗液中蛋白含量,计算肺通透指数;酶谱法测肺组织匀浆液和支气管肺泡灌洗液上清中MMP-2、MMP-9酶活力及免疫组织化学方法检测肺组织MMP-2、MMP-9蛋白表达情况;并进行肺组织形态学观察。结果酶谱法显示:与LPS组相比,SBTI组大鼠肺组织、支气管肺泡灌洗液中MMP-2、MMP-9活性明显下降,在d7活性变化明显,但MMP-9变化较MMP-2更明显。免疫组化显示MMP-2、MMP-9在LPS组肺组织细胞高表达。SBTI组大鼠肺组织MMP-2、MMP-9表达明显减弱。肺组织病理提示SBTI治疗组肺损伤病变局限且程度较轻,肺泡内渗出明显小于LPS组,PMN和红细胞渗出较少。结论MMP-2、MMP-9在LPS诱导大鼠急性肺损伤中发挥重要的作用,SBTI通过抑制MMPs的分泌及激活,降低基底膜的降解,减轻肺水肿及炎症反应,发挥肺保护的作用。     

脂多糖诱导大鼠急性肺损伤中钠氢交换体的表达

目的:建立脂多糖诱导大鼠急性肺损伤实验模型,观察实验模型中大鼠肺组织上钠氢交换体1mRNA和蛋白的表达水平变化情况。方法:40只(250~350g)雄性清洁级SD大鼠随机均分成空白对照组(C组)、脂多糖2h组(L-2h组)、脂多糖4h组(L-4h组)和脂多糖6h组(L-6h组)。监测各组大鼠基本生命体征;光学显微镜下观察大鼠肺组织病理改变;计算急性肺损伤评分和肺组织湿/干重比值;检测支气管肺泡灌洗液中总蛋白、肿瘤坏死因子-α和巨噬细胞炎性蛋白的浓度;测定肺组织髓过氧化物酶活性;免疫组化、RT-PCR和Western Blot检测肺组织钠氢交换体1mRNA和蛋白的表达水平。结果:空白对照组大鼠肺组织肺泡结构正常,肺泡腔无渗出物;脂多糖各组大鼠肺组织病理改变明显,肺泡间隔增厚,肺泡腔内可见较多的炎性细胞,肺泡腔内有血性渗出液。和空白对照组比较,脂多糖各组大鼠支气管肺泡灌洗液中总蛋白、肿瘤坏死因子-α和巨噬细胞炎性蛋白的浓度均依次明显增高(FTP=31.67、FTNF-α=275.33、FMIP-2=239.26,均P<0.05);肺组织急性损伤评分、湿/干重比、髓过氧化物酶活性、钠氢交换体1的免疫组化表达水平、钠...     

乌司他丁上调水通道蛋白1保护新生猪体外循环肺缺血/再灌注损伤

目的探讨乌司他丁对新生猪体外循环肺缺血/再灌注后的保护作用以及水通道蛋白1(aquaporin 1,AQP1)在此病理过程中的表达。方法 12只健康新生猪依据主动脉开放前是否通过肺动脉注射乌司他丁,随机分为两组:对照组(control,n=6)和实验组(test,n=6),实验组在主动脉开放前通过肺动脉注射乌司他丁10 000 U.kg-1(0.154 mol.L-1生理盐水稀释至30 ml)。在开胸后即刻(T1)、主动脉开放90 min实验结束前(T2)留取肺泡灌洗液、肺组织标本和肺静脉血标本。光镜观察并盲法评分比较肺组织病理学变化;检测肺泡灌洗液中性粒细胞(PMN)计数;酶联免疫吸附法检测肺静脉血清白介素6(IL-6)和肿瘤坏死因子α(TNF-α)含量;肺组织湿干重比(wet/dry weight,W/D);免疫组化和Western blot检测肺组织AQP1表达。结果两组相比,实验组肺组织病理变化明显减轻;肺泡灌洗液中性粒细胞(PMN)计数、IL-6、TNF-α和肺组织湿干重比明显降低以及AQP1表达明显提高(P<0.05)。结论乌司他丁对新生猪体外循环肺缺血/再灌注损伤具有一定的保护作用,可能的作用机制与其促进AQP1蛋白表达有关。     

长期雾化吸入4种非雾化剂型药物对健康SD大鼠肺组织的影响

目的:研究长期雾化吸入4种非雾化剂型药物对健康SD大鼠肺组织的损伤情况,评价其雾化吸入的安全性。方法:将40只健康SD大鼠(♂)按随机数字表法分为8组,分别为空白对照组、生理盐水组(溶剂对照)、布地奈德组(雾化剂型药物对照,0.1g/L)、二氧化硅组(肺损伤药物对照,40 g/L)和4种非雾化剂型药物组[定喘汤组(15 g/mL,以生药量计)、头孢曲松组(200 g/L)、清开灵组(原液)和痰热清组(原液)],每组5只。除空白对照组大鼠不作处理外,其余各组大鼠均雾化吸入给药,给药体积均为10mL,每天给药2次,连续给药56 d。给药结束后,对其外周血中白细胞进行分类、计数以及对支气管肺泡灌洗液中白细胞进行计数;苏木精-伊红染色观察其肺组织病理变化并进行尘细胞计数;免疫组化法检测其肺组织中白细胞分化抗原163(CD163)表达水平。结果:各组大鼠外周血中白细胞分类主要有淋巴细胞和中性粒细胞,其中又以淋巴细胞为主。与空白对照组比较,生理盐水组大鼠外周血中白细胞、淋巴细胞、中性粒细胞计数和肺泡灌洗液中白细胞计数以及肺组织中尘细胞计数差异均无统计学意义(P>0.05);支气管及肺组织结构完整,CD163表达为阴性。与生理盐水组比较,布地奈德组大鼠上述指标差异均无统计学意义(P>0.05),支气管及肺组织结构完整,CD163表达为阴性;而其余5组大鼠外周血中白细胞、淋巴细胞、中性粒细胞计数和支气管肺泡灌洗液中白细胞计数以及肺组织中尘细胞计数均显著升高(P<0.05);肺组织发生不同程度的肺泡壁增厚、肺泡间质水肿等病理变化,CD163表达均为阳性或强阳性。结论:4种非雾化剂型药物长期雾化吸入后可引起健康SD大鼠肺组织不同程度的病理改变,炎症细胞计数升高,肺泡中出现尘细胞。     

参麦注射液对肺缺血-再灌注损伤时Fas/FasL表达的影响

目的:探讨参麦注射液对肺缺血-再灌注损伤(PIRI)时Fas/FasL配体(Fas/FasL)表达的影响。方法:采用在体兔单肺原位缺血-再灌注模型。实验兔30只,随机分为假手术对照组(sham,n=10)、肺缺血-再灌注组(I-R,n=10)和肺缺血-再灌注加参麦注射液组(SM,n=10)。分别于再灌注3h取左肺组织,观察Fas/FasLmRNA定位表达、凋亡指数(AI)、肺组织湿干重比(W/D)、肺损伤组织学定量评价指标(IQA)及光镜、电镜下的组织形态学改变。结果:SM组Fas/FasLmRNA在肺小动脉内(外)膜、肺小静脉内膜、肺泡上皮及肺支气管上皮呈弱阳性表达,明显低于I-R组(P<0.05);AI、W/D和IQA值显著低于I-R组(P<0.01和P<0.05);肺组织形态学异常改变程度减轻。结论:参麦注射液可下调肺组织Fas/FasLmRNA的表达而减轻细胞凋亡,对PIRI发挥积极的防治作用。     

支气管肺泡灌洗氨溴索治疗急性肺脓肿的效果观察

目的：探讨支气管肺泡灌洗氨溴索治疗急性肺脓肿的临床疗效。方法：选取我院收治的急性肺脓肿患者97例,采用随机数字表法分为观察组（n=49）和对照组（n=48）。对照组采用抗生素和气管肺泡灌洗生理盐水治疗,观察组采用支气管肺泡灌洗氨溴索治疗。分析比较两组临床疗效,灌洗次数、用药时间和不良反应发生率。结果：观察组临床疗效优于对照组,差异有统计学意义（P<0.05）;观察组灌洗次数和用药时间小于对照组,差异有统计学意义（P<0.05）;两组均未观察到明显不良反应。结论：使用支气管肺泡灌洗氨溴索治疗急性肺脓肿疗效显著,安全性高,值得推广。     

阿奇霉素对哮喘致敏大鼠气道炎症及Th1/Th2失衡的调节作用

目的:探讨阿奇霉素对哮喘(OVA)致敏大鼠气道炎症及Th1/Th2失衡的调节作用。方法:SD大鼠40只,随机分为生理盐水组、哮喘模型组、地塞米松组以及阿奇霉素组,每组10只。利用卵白蛋白(Ovalbumin,OVA)/Al(OH)3致敏与OVA雾化吸入激发建立大鼠过敏性气道炎症模型,收集肺泡灌洗液(BALF)进行白细胞分类计数。采用ELISA法测定肺泡灌洗液中IL-2、IL-4、TNF-α与ET-1的表达情况。光镜观察肺组织病理结构变化。结果:OVA模型大鼠肺泡灌洗液中的中性粒细胞、淋巴细胞以及嗜酸性粒细胞含量明显增加;HE染色观察肺组织病理结构出现明显的支气管上皮脱落、杯状细胞增生,支气管周围嗜酸性粒细胞明显浸润现象;BALF中IL-2、IL-4、TNF-α与ET-1的表达均明显高于生理盐水对照组(P<0.05)。阿奇霉素则显著降低肺泡灌洗液中中性粒细胞、淋巴细胞以及嗜酸性粒细胞含量;明显改善支气管上皮脱落、杯状细胞增生,支气管周围嗜酸性粒细胞浸润现象;BALF中IL-2、IL-4、TNF-α与ET-1的表达也明显低于OVA模型大鼠(P<0.05)。结论:阿奇霉素通过调节Th1/Th2失衡对过敏性哮喘的气道炎症具有明显的治疗作用。     

白蛋白对幼兔胎粪吸入综合征的保护作用及机制研究

目的:探讨白蛋白对胎粪吸入综合征的保护作用及机制。方法:将28只幼兔分为模型组(n=12)、白蛋白组(n=12)和正常对照组(n=4),建立幼兔胎粪吸入模型;在胎粪吸入后8、16、24小时计数支气管肺泡灌洗液(BALF)白细胞(WBC)、中性粒细胞(PMN),并采用放射免疫法测定肺组织匀浆液及BALF中IL-8含量,在显微镜下观察肺损伤的程度。结果:同对照组相比,模型组BALF中PMN和WBC数升高,肺组织匀浆液和BALF中IL-8含量明显升高,差异有极显著性(P<0.01),且肺组织病理改变明显。同对照组相比,白蛋白组上述指标呈现类似改变,而同模型组相应时间点相比,白蛋白组上述指标降低,差异有极显著性(P<0.01),肺损伤程度明显减轻。结论:幼兔胎粪吸入后,肺部产生明显的炎症反应,IL-8在胎粪吸入综合征的发生发展中占有重要的作用;白蛋白可通过减少IL-8的分泌,保护胎粪吸入所致的肺损伤。     

Inhibition of poly(ADP-ribose) polymerase attenuates lung tissue damage after hind limb ischemia-reperfusion in rats.

The objective of this study was to investigate the effects of 3-aminobenzamide (3-AB) on tissue damage in lung after hind limb ischemia-reperfusion (I/R), by assessing blood biochemical assay and histopathological analysis. Thirty-five adult Wistar rats were divided into five groups. After application of anaesthesia both hind limbs were occluded with tourniquets. Following ischemia period for 60 min, the tourniquets were removed allowing reperfusion for 120 min. The IR group received 0.5 ml of saline while the IR+AB group received 3-AB (10 mgkg(-1) intraperitoneally). The IR+DMSO group was given 0.5 ml 10% DMSO 30 min before the removal of the tourniquets. The control group received 0.5 ml saline and the AB group received 0.5 ml 3-AB (10 mgkg(-1)) intraperitoneally. At the end of the reperfusion period, mid-line sternotomy was performed. Blood samples were taken with cardiac puncture. Bronchoalveolar lavage (BAL) of the left lung was performed with saline. Right lung was preserved for histopathological evaluation and biochemical examination. Lung tissue malondialdehyde (MDA) and 3-nitrotyrosine levels, myeloperoxidase and Na+/K+ ATP-ase activities, wet to dry weight ratios, and plasma and BAL fluid MDA levels were determined. Histopathological evaluation was performed, too. Hind limb IR caused significant increase in the lung tissue 3-NT to total tyrosine ratio (p = 0.014), wet to dry weight ratio (p = 0.000), MPO activity (p = 0.000), and MDA levels (p = 0.000). The animals treated with 3-AB showed a statistically significant decrease in these values (p < 0.05). Na+/K+ ATP-ase activity which was found to be decreased significantly with IR, returned to near normal levels with 3-AB treatment. Additionally, lung tissue injury in IR group characterized with moderate interstitial congestion and neutrophil infiltration, showed remarkable amelioration following 3-AB treatment. Our results strongly support the view that poly(ADP-ribose) polymerase (PARP) plays an important role in the inflammatory process in hind limb I/R-induced lung injury and as a PARP inhibitor, 3-AB seems to have a potential to treat this inflammatory injury.     

Dexamethasone treatment attenuates early seawater instillation-induced acute lung injury in rabbits.

There is very little evidence on the value of giving corticoids in cases of seawater drowning induced acute lung injury/acute respiratory distress syndrome (ALI/ARDS). Therefore, this study aimed to investigate whether dexamethasone treatment can attenuate seawater instillation-induced acute lung injury in rabbits. Seawater (4 ml/kg body weight) was instilled into the lower trachea of ventilated, anesthetized rabbits. Then these rabbits were assigned randomly 20 min later to receive intravenous injection of 1mg/kg body weight of dexamethasone (dissolving in 2 ml of normal saline) or 2 ml of normal saline. All animals demonstrated immediate drops in arterial oxygen tension (PaO2) and the total thoracic compliance, which were significantly improved after 2 h of dexamethasone treatment. Histopathological study also indicated that dexamethasone treatment markedly attenuated lung histopathological changes, alveolar hemorrhage and inflammatory cells infiltration with evidence of decreasing of myeloperoxidase (MPO) activity and tumor necrosis factor-alpha (TNF-alpha) concentration in lung tissue. In addition, dexamethasone treatment reduced extravascular lung water and lung epithelial-endothelial barrier permeability, up-regulated the expression of surfactant protein-A (SP-A) and alpha-epithelial Na+ channel, and increased Na+/K+-adenosine triphosphatase (Na+/K+-ATPase) activity and Na+/K+-ATPase-alpha1 protein abundance. Thus, these data indicate that dexamethasone treatment might be of benefit in patients with seawater aspiration-induced ALI.     

Asbestos exposure dose-bronchoalveolar milieu response in asbestos workers and the sheep model: evidences of a threshold for chrysotile-induced fibrosis

Epidemiological studies of asbestos workers have proposed a linear dose-response relationship between asbestos cumulative exposure indices and the incidence of asbestos-related lung diseases. However, for chrysotile, several studies have not observed such a linear relationship in low exposure workers. To further study the relationship of chrysotile exposure dose - lung tissue response, we designed in the sheep model one experiment of one exposure at variable intensity and one experiment with variable rates of individual exposures. In the first study, 6 groups of 6 sheep were exposed to either 0, 1, 10, 25, 50 or 100 mg chrysotile in 100 ml saline and lung lavage analyses carried out at day 0, 12, 24, 40 and 60 after. Histopathology was done at day 60. In the second experiment, 4 groups of 12 sheep were exposed to 100 ml saline every week or every two weeks, 100 mg chrysotile in 100 ml saline every week or every two weeks. In the second experiment, lung damage was assessed by changes in vital capacity (VC), lung compliance (Cst) and profusion of chest radiographic opacities (PO). On BAL in the control sheep, there were small and transient early increases in total cells/ml, macrophages/ml, neutrophils/ml, lactate dehydrogenase (LDH)/ml, alkaline phosphatase (AK)/ml, beta-glucuronidase (beta G)/ml and procollagen lll/ml. In the 1, 10, 25, and 50 mg asbestos sheep groups, there were no significant differences. However, in the 100 mg asbestos sheep, there were significant sustained increases in total cells/ml (3-6 times controls), macrophages/ml (2-6 times controls), neutrophils/ml (60-600 times controls), LDH/ml (5-10 times controls), AK/ml (1.5-2 times controls), beta G/ml (3-5 times controls), procollagen lll/ml (2 times controls) and IgG (1.5-3 times controls). These data were correlated with histopathological findings. In the sheep exposed weekly to chrysotile, significant changes in VC, Cst and PO occurred at mean cumulative exposure dose of 1.2 g whereas in the sheep exposed every 2 weeks, similar changes in VC, Cst and PO occurred at the cumulative exposure dose of 3.6 g (P less than 0.05). In conclusion, our data suggest that there is a threshold for chrysotile-induced fibrosis. This level cannot be considered adequately in term of cumulative exposure dose but must take into account intensity and rate of individual exposures.     

Effect of betulinic acid on neutrophil recruitment and inflammatory mediator expression in lipopolysaccharide-induced lung inflammation in rats

This study aimed to evaluate the effect of betulinic acid (BA) on acute lung damage induced by bacterial endotoxin (lipopolysaccharide, LPS) in male Sprague-Dawley rats and explore its possible mechanisms. Oral administration of 25 (mg/kg) BA started 7 days before LPS or saline nasal installation. Twenty-four hours after LPS or saline installation, samples of lung tissues were collected for determination of level of lipid peroxidation (MDA), reduced glutathione (GSH), superoxide dismutase (SOD), and expression of tumor necrosis-α (TNF-α), transforming growth factor-β1 (TGF-β1) and inducible nitric oxide synthase (iNOS). Histopathology was done to examine pathological changes in lungs. Wet/dry (W/D) ratio and capillary protein leakage were also determined. Bronchoalveolar lavage (BAL) fluid was carried out for quantification of airway cellular inflammation and nitrate/nitrite (NOx) level. In comparison to BAL fluid samples from control animals, LPS-stimulated animals exhibited a higher count of the inflammatory cells and increased NOx levels. Lungs from LPS-treated animals showed increased lipid peroxidation, altered activities of antioxidant enzymes (GSH and SOD) and increased expression of TNF-α, TGF-β1 and iNOS in comparison to lungs from control animals. LPS installation-induced pulmonary edema, manifested by significant increase in lung W/D ratio and Evans blue extravasation in lung tissue. This was supported by the histopathological examination which revealed markedly inflamed lung in LPS-treated animals. Treatment with BA was found to significantly attenuate all these alterations. The present results suggest that BA is endowed with antiinflammatory and antioxidant properties that protect the lung against the deleterious actions of LPS.     

Asbestos Exposure Dose - Bronchoalveolar Milieu Response in Asbestos Workers and the Sheep Model: Evidences of a Threshold for Chrysotile-Induced Fibrosis

ABSTRACT

Epidemiological studies of asbestos workers have proposed a linear dose-response relationship between asbestos cumulative exposure indices and the incidence of asbestos-related lung diseases. However, for chrysotile, several studies have not observed such a linear relationship in low exposure workers. To further study the relationship of chrysotile exposure dose - lung tissue response, we designed in the sheep model one experiment of one exposure at variable intensity and one experiment with variable rates of individual exposures. In the first study, 6 groups of 6 sheep were exposed to either 0, 1, 10, 25, 50 or 100 mg chrysotile in 100 ml saline and lung lavage analyses carried out at day 0, 12, 24, 40 and 60 after. Histopathology was done at day 60. In the second experiment, 4 groups of 12 sheep were exposed to 100 ml saline every week or every two weeks, 100 mg chrysotile in 100 ml saline every week or every two weeks. In the second experiment, lung damage was assessed by changes in vital capacity (VC), lung compliance (C_st) and profusion of chest radiographic opacities (PO). On BAL in the control sheep, there were small and transient early increases in total cells/ml, macrophages/ml, neutrophils/ml, lactate dehydrogenase (LDH)/ml, alkaline phosphatase (AK)/ml, β-glucuronidase (βG)/ml and procollagen III/ml. In the 1, 10, 25, and 50 mg asbestos sheep groups, there were no significant differences. However, in the 100 mg asbestos sheep, there were significant sustained increases in total cells/ml (3-6 times controls), macrophages/ml (2-6 times controls), neutrophils/ml (60 - 600 times controls), LDH/ml (5 - 10 times controls), AK/ml (1.5 - 2 times controls), BC/ml (3-5 times controls), procollagen III/ml (2 times controls) and IgC (1.5 - 3 times controls). These data were correlated with histopathological findings. In the sheep exposed weekly to chrysotile, significant changes in VC, C_st and PO occurred at mean cumulative exposure dose of 1.2 9 whereas in the sheep exposed every 2 weeks, similar changes in VC, C_St and PO occurred at the cumulative exposure dose of 3.6 g (P < 0.05). In conclusion, our data suggest that there is a threshold for chrysotile-induced fibrosis. This level cannot be considered adequately in term of cumulative exposure dose but must take into account intensity and rate of individual exposures.     

不同时期全肺灌洗对实验性肺纤维化兔的血气和病理干预效果

目的观察不同时期全肺灌洗对实验性肺纤维化兔的血气和病理干预效果,以明确全肺灌洗治疗的效果及灌洗时机的选择。方法将兔随机分成3组,其中对照组气管内灌注2ml生理盐水,模型组和实验组一次性灌注平阳霉素进行模型复制,而后各组在不同时期全肺灌洗,在第6周末对比各组血气和病理差异。结果（1）动脉血氧分压：模型组、14d组、21d组显著（P〈0．01）低于对照组;（2）肺纤维化：模型组与对照组比较有显著差别（P〈O．01）。结论早期灌洗对实验性肺纤维化兔可以显著提高动脉血PO2,且可一定程度减轻肺纤维化,延缓病情的进展。     

大鼠肺孢子虫肺炎肺脏病理学变化的动态研究

目的研究大鼠肺孢子虫肺炎（PCP）不同病程的动态病理学变化。方法将雌性清洁级SD大鼠50只随机分成实验组和对照组，每组25只。实验组采用皮下注射地塞米松1mg／只／次、每周2次免疫抑制的方法诱导建立PCP的动物模型，对照组则注射相同剂量的灭菌生理盐水。在所有大鼠的饮水中加入1g／L盐酸四环素预防继发性细菌感染。免疫抑制3、5、7、9、11周后．每组各取5只大鼠进行解剖，分别制作肺组织印片，姬氏染色，检香肺孢子虫包囊，同时制作肺组织病理切片，HE染色，观察肺组织的病理学变化。结果用地塞米松诱导大鼠3周，其肺组织印片术查见肺孢子虫包囊，肺组织也未见明显的病理学改变；第5周，肺组织印片州均查见肺孢予虫包囊，肺组织出现病理学改变。并且病理学孜变随诱导时间的增加而加重；第7周主要表现为肺泡壁毛细血管轻度充血，间质内慢性炎性细胞浸润；至第9周至11周，则可见间质细胞增生、间质水肿、肺泡内出现粉红色泡沫样渗出物，部分肺组织呈现大片状实变区。对照组大鼠无异常表现，病原学检查阴性，肺脏组织无明显的病理学改变。结论应用皮下注射地塞米松免疫抑制诱导方法可成功建立肺孢子虫肺炎的大鼠实验模型，大鼠肺孢子虫肺炎的病理学改变以炎症、渗出、细胞浸润、间质细胞增生等为主．同时病理学改变随病程进展而加重。     

芍药苷对大鼠低氧性肺动脉高压的防治作用及其抗氧化机制研究

目的 研究芍药苷对低氧诱导的肺动脉高压大鼠模型的作用并初步探讨其作用机制。方法 60只SD大鼠随机分为6组,每组10只,分别为：对照组（等体积生理盐水,ig）、模型组（等体积生理盐水,ig）、阳性对照组（西地那非25 mg/kg,ig）、芍药苷低、中、高剂量组（20、40、80 mg/kg,ig）。对照组大鼠置于正常环境中饲养,其余各组均于给药0.5 h后置于全自动低压低氧舱内（大气压50 kPa,氧浓度10%）,每天8 h,持续21 d。在实验终点时检测各组大鼠平均肺动脉压（mPAP）、平均颈动脉压（mCAP）、右心室肥厚指数（RVHI）及观察肺动脉病理变化;检测血浆内皮素（ET-1）、血清一氧化氮（NO）水平;检测肺组织匀浆超氧化物歧化酶（SOD）、过氧化氢酶（CAT）、谷胱甘肽过氧化物酶（GSH-Px）活性、丙二醛（MDA）含量。结果 与对照组比较,模型组大鼠mPAP、RVHI、血浆ET-1水平、肺组织中MDA含量显著升高（P＜0.01）,血清中NO水平、肺组织中SOD、CAT、GSH-Px活性显著降低（P＜0.01）,HE染色显示大鼠肺小动脉管壁明显增厚,管腔狭窄。与模型组比较,芍药苷中、高剂量组大鼠mPAP、RVHI、血浆ET-1水平、肺组织中MDA含量显著降低（P＜0.05或P＜0.01）,血清中NO水平、肺组织中SOD、CAT、GSH-Px活性显著升高（P＜0.05或P＜0.01）;HE染色显示不同剂量芍药苷干预后,大鼠肺小动脉管壁增厚和管腔狭窄均不同程度减轻。结论 芍药苷可降低低氧诱导的大鼠肺动脉高压与右心室肥厚程度,减轻肺小动脉血管重塑,其机制可能与降低大鼠血浆ET-1水平、升高血清NO水平,改善血管内皮舒缩因子失衡,提高大鼠肺组织匀浆中SOD、CAT、GSH-Px活性、降低MDA含量,减轻大鼠肺组织氧化应激损伤有关。     

三七总皂甙对兔肺挫伤治疗作用的实验研究

目的 采用重物自由落体复制兔肺挫伤模型,通过检测炎症因子白介素-1β(interleukin-1β,IL-lβ),氧化应激指标脂质过氧化产物丙二醛 (malondialdehyde,MDA)及髓过氧化物酶(myeloperoxidase,MPO)水平,并结合肺组织湿干比重及病理变化,探讨三七总皂甙(panax noto...