磷脂酰肌醇3激酶对哮喘大鼠气道上皮细胞诱导型一氧化氮合酶表达的调控作用

目的： 探讨磷脂酰肌醇3激酶（PI3K）抑制剂wortmannin对哮喘大鼠支气管上皮细胞诱导型一氧化氮合酶（iNOS）表达的影响。方法: 24只成年哮喘大鼠随机分成对照组、哮喘组以及PI3K抑制剂wortmannin干预组。对支气管肺泡灌洗液（BALF）细胞总数及嗜酸性粒细胞进行计数,免疫组织化学检测大鼠支气管上皮细胞iNOS蛋白的表达,RT-PCR检测肺组织iNOS mRNA的表达,分光光度计检测肺组织PI3K活性、iNOS活性及NO含量。结果: 哮喘组大鼠BALF细胞总数计数及嗜酸性粒细胞分类均高于对照组;PI3K抑制剂wortmannin干预组BALF嗜酸性粒细胞计数及分类明显低于哮喘组,差异显著。哮喘组肺组织PI3K活性、iNOS活性及NO含量高于对照组,PI3K抑制剂wortmannin干预组肺组织PI3K活性、iNOS活性及NO含量低于哮喘组。哮喘组大鼠支气管上皮细胞iNOS蛋白及肺组织iNOS mRNA表达较对照组明显增强,但PI3K抑制剂wortmannin组iNOS蛋白及mRNA表达均明显弱于哮喘组。结论: PI3K可调节哮喘大鼠气道iNOS表达,影响哮喘气道炎症反应。     

IL-31RA基因敲除对哮喘小鼠气道炎症的影响

目的本研究通过构建IL-31RA基因敲除小鼠模型及哮喘模型,观察该基因敲除对哮喘小鼠气道炎症的影响。方法采用OVA建立小鼠哮喘模型,于末次激发后取肺组织HE染色及甲苯胺蓝染色观察肺部炎症细胞浸润和肥大细胞增生情况,支气管肺泡灌洗液(BALF)白细胞及嗜酸性粒细胞(EOS)计数,ELISA法检测血浆中总Ig E、IFN-γ、IL-4水平。结果成功构建IL-31RA基因敲除小鼠模型及哮喘模型,哮喘小鼠BALF中白细胞总数、嗜酸性粒细胞百分比和血浆中Ig E水平明显增多,基因敲除哮喘小鼠较野生型哮喘小鼠增多更明显。哮喘小鼠肺组织病理切片EOS、肥大细胞浸润,基因敲除小鼠较野生型小鼠EOS、肥大细胞浸润增多。哮喘小鼠血浆中Th2类细胞因子IL-4水平明显高于正常对照组,Th1类细胞因子IFN-γ水平明显低于对照组,且基因敲除哮喘小鼠IL-4水平较野生型哮喘小鼠增高。结论 IL-31受体A信号可抑制哮喘小鼠气道的炎症反应。     

IL-27对哮喘小鼠气道炎症的影响

目的研究IL-27对卵白蛋白(OVA)激发哮喘小鼠气道炎症的影响。方法 24只雌性BALB/c小鼠随机分为生理盐水组、哮喘组及IL-27组,每组8只。应用OVA建立哮喘模型,IL-27组小鼠应用1μgIL-27(溶于50μlPBS中)滴鼻给药,观察3组小鼠肺组织病理改变,计数支气管肺泡灌洗液(BALF)中嗜酸性粒细胞;ELISA法测定小鼠BALF中IL-4和IFN-γ浓度,RT-PCR测定肺组织T-bet mRNA的表达量。结果 IL-27组小鼠肺组织炎症反应明显轻于哮喘组小鼠;IL-27组小鼠BALF中嗜酸性粒细胞计数为(2.21±0.33)×107/L明显低于哮喘组的(12.82±2.17)×107/L(P0.01);IL-27组小鼠BALF中IL-4浓度为(20.4±3.2)μg/L,明显低于哮喘组的(61.3±13.1)μg/L(P0.05);IL-27组小鼠BALF中IFN-γ浓度为(50.3±6.3)μg/L,明显高于哮喘组的(11.1±3.3)μg/L(P0.05);IL-27组小鼠肺组织T-bet mRNA表达量(吸光度积分比值)为(0.268±0.048),明显高于哮喘组的(0.130±0.012)(P0.05)。结论 IL-27可能通过增强T-bet mRNA的表达增强Th1反应,减少BALF中嗜酸性粒细胞数量,进而减轻了哮喘小鼠肺组织炎症反应。     

原癌基因表达与哮喘气道炎症

目的:观察原癌基因表达与气道炎症细胞浸润的关系。方法:卵蛋白致敏豚鼠,复制哮喘模型。Dot-blot\,Northern-blot分子杂交及免疫组织化学技术观察哮喘发作前、后豚鼠气道上皮及肺组织中c-fos\,c-myc\,c-jun和c-sis的表达及其与炎症细胞浸润的关系。结果:正常豚鼠气道及肺组织中c-fos\,c-mycmRNA无或很少表达,极少炎症细胞浸润。哮喘发作后,豚鼠气道上皮及肺组织c-fos\,c-mycmRNA表达明显增加。免疫组织化学研究显示Fos、Myc、Jun及Sis在正常豚鼠气道及肺组织低水平表达,哮喘发作后即刻,4种原癌基因表达产物明显增加,气道内有少量淋巴细胞、嗜酸性粒细胞及中性粒细胞浸润;12-24h,上述细胞浸润加重,粘膜下层及粘膜上皮内以中性粒细胞和嗜酸性粒细胞浸润为主。结论:原癌基因表达与气道炎症在哮喘发病中有密切关系。     

活菌卡介苗对哮喘小鼠IL-17的调节作用

目的初步探讨活菌卡介苗（BCG）对哮喘小鼠IL-17的调节作用。方法 4周龄雌性Balb/c小鼠30只随机分为A组（对照组）、B组（哮喘组）和C组（BCG干预组）,每组各10只。B、C两组予OVA腹腔注射致敏、OVA雾化诱发哮喘,C组在致敏前14d接种BCG。HE染色观察小鼠肺部病理改变,计数支气管肺泡灌洗液（bronchoalveolar lavage fluid,BALF）中细胞总数并分类,酶联免疫吸附试验（ELISA）检测血清及BALF中白介素-17（IL-17）含量。结果肺组织病理观察显示A组气管周围基本无炎症细胞浸润,B组支气管周围大量炎症细胞浸润,杯状细胞增生,C组炎症较B组减轻。B、C组BALF中细胞总数和嗜酸性粒细胞、淋巴细胞百分率均显著高于对照组（P〈0.01）,而C组嗜酸性粒细胞比例则明显低于B组（P〈0.01）。B、C组小鼠血清、BALF中IL-17含量高于A组（P〈0.01）,而C组则明显低于B组（P〈0.01）。各组小鼠血清及BALF中IL-17水平与BALF中嗜酸性粒细胞呈正相关（P〈0.01）。结论 BCG接种可抑制IL-17的产生,减轻哮喘小鼠气道炎症反应。     

转录因子GATA-3 mRNA在哮喘模型小鼠体内的表达

目的:探讨转录因子GATA-3 mRNA在哮喘模型小鼠体内的表达。 方法:建立卵白蛋白（OVA）致小鼠哮喘模型，计数支气管肺泡灌洗液（BALF）中炎症细胞总数和分类，评价肺组织炎症细胞浸润；ELISA检测BALF和脾细胞培养上清液中IL-4和IFN-γ浓度；RT-PCR检测脾细胞和肺组织GATA-3 mRNA表达水平。 结果:哮喘组BALF中炎症细胞总数及嗜酸粒细胞百分比明显高于对照组，支气管出现明显炎症细胞浸润、黏液分泌和支气管收缩，BALF和脾细胞培养上清液中IL-4明显高于对照组，肺组织和脾细胞GATA-3 mRNA表达水平均明显高于对照组。 结论:哮喘模型小鼠肺组织和脾细胞GATA-3 mRNA表达增加，可能在促进Th2细胞因子合成和介导气道炎症细胞浸润中具有重要作用。     

IL-4RA基因转染对哮喘模型的干预性作用研究

目的IL-4RA基因转染对哮喘模型过敏性炎症的干预性研究。方法选择雌性BALB／c小鼠作为动物模型，随机分为5组（每组10只）：空白对照组、哮喘模型组、空载体（10^4CFU/ml pLNC-laz）干预组、激素治疗组、目的基因（10^4CFU/ml pLNC-IL-4RA）干预组。各组在最后一次激发后24h放血杀死小鼠，检测血中嗜酸性粒细胞（eosinophils，EOS）计数，用ELISA检测支气管肺泡灌洗液（broncho alveolar lavage fluid，BALF）中的各种细胞因子水平，并对BALF中各种炎症细胞计数，肺组织切片做HE染色。结果哮喘模型鼠BALF中有大量嗜酸性粒细胞浸润，肺组织病理切片可见大量炎症细胞浸润、杯状细胞增生、黏膜壁破坏。哮喘模型的这些改变在激素和基因干预后明显减轻，差异有统计学意义（P〈0．01），而在空载体干预后则无明显的变化（P〉0．05）。空白对照组的BALF中IL-5、IL-13低于检测水平，哮喘模型组BALF中IL-5、IL-13水平明显增高，而基因治疗组和激素治疗组IL-5、IL-13水平明显减少，差异有统计学意义（P〈0．01），空载体干预组BALF中细胞因子水平与哮喘模型组比较差异无统计学意义（P〉0．05）。结论通过逆转录病毒转染的IL-4RA的基因高表达成功地阻止在哮喘模型鼠气道由Ⅱ，4和IL-13诱发的气道嗜酸性粒细胞浸润，另外，逆转录病毒介导的IL-4RA在气道的表达明显地阻止了哮喘模型气道黏液的分泌，同时也减少了过敏性哮喘相关的TH2细胞因子水平，因此，基因治疗可能会成为治疗慢性哮喘气道炎症和哮喘症状的极有潜力的药物。     

IL-31在哮喘小鼠中的动态表达及对肺泡上皮细胞表达CCL11和CCL22的影响

目的通过观察IL-31在OVA诱导小鼠哮喘模型中的动态表达及IL-31对肺泡上皮细胞表达趋化因子CCL11和CCL22的影响,探讨IL-31在哮喘气道炎症中的作用。方法常规OVA法建立小鼠哮喘模型,于末次激发后取肺组织HE染色及AB-PAS染色,收集支气管肺泡灌洗液(BALF)进行白细胞和嗜酸性粒细胞(EOS)计数,ELISA法检测血浆中IgE、IL-4、IFN-γ、IL-31水平,荧光定量PCR检测肺组织IL-31R mRNA表达水平,同时体外培养小鼠肺泡上皮细胞,用IL-31处理24 h后检测CCL11和CCL22 mRNA的表达水平。结果成功构建哮喘小鼠模型,哮喘小鼠BALF中白细胞总数、嗜酸性粒细胞百分比和血浆中IgE水平明显增多。哮喘小鼠肺组织病理切片见中性粒细胞、EOS浸润。哮喘小鼠血浆中Th2类细胞因子IL-4水平明显高于对照组,Th1类细胞因子IFN-γ明显低于对照组。哮喘小鼠血浆IL-31水平和肺组织IL-31R mRNA表达水平明显增高,第2周至第8周虽略有降低但仍明显高于对照组。IL-31作用小鼠肺泡上皮细胞24h后,趋化因子CCL11、CCL22mRNA表达增高。结论IL-31通过刺激趋化因子表达募集炎性细胞,促进气道炎症的发生发展。     

地塞米松对哮喘大鼠嗜酸性粒细胞中p53表达的影响

目的： 研究支气管哮喘支气管肺泡灌洗液（BALF）嗜酸性粒细胞中凋亡相关基因p53的表达以及地塞米松对其的作用及其机制。方法： 将36只大鼠随机分为对照组、哮喘组和激素组，并对其BALF的嗜酸性粒细胞进行计数，以免疫印迹法(Western blotting)检测嗜酸性粒细胞中p53的表达。结果： 哮喘组BALF的 总细胞数及嗜酸性粒细胞均高于激素组及对照组（P<0.01）。哮喘组BALF的嗜酸性粒细胞中p53表达弱于激素组和对照组（P<0.01）。结论： 哮喘气道炎症与嗜酸性粒细胞生存增加亦即嗜酸细胞凋亡减少密切相关。糖皮质激素可诱导嗜酸性粒细胞凋亡，其机制可能与促嗜酸性粒细胞凋亡的p53表达有关。     

吸入低氧气体对哮喘缓解期豚鼠嗜酸性粒细胞和CD4+T淋巴细胞的影响

目的:探讨吸入低氧气体防治哮喘的机制。方法:采用10%卵蛋白致敏和5次1%卵蛋白吸入诱发复制哮喘豚鼠模型,设立正常组、哮喘组和低氧吸入组3组。用(13.0±0.5)% O₂/N₂低氧气体吸入干预哮喘缓解期豚鼠,结束时3组均作血清皮质醇、支气管肺泡灌洗液(BALF)中嗜酸性粒细胞(EOS)计数与低密度EOS(HEOS)百分率和外周血CD₄⁺T淋巴细胞数量以及气道平滑肌张力的测定。结果: ①正常组和低氧吸入组的血清皮质醇含量均非常显著高于哮喘组(P＜0.01)。②低氧吸入组BALF中EOS绝对值及HEOS百分率均数均非常显著低于哮喘组(P＜0.01)。③正常组和低氧吸入组外周血CD₄⁺T淋巴细胞数量明显低于哮喘组(P＜0.01)。④哮喘组气道平滑肌张力增高。 结论:低氧吸入治疗能使哮喘缓解期豚鼠血清皮质醇升高,从而使其BALF中EOS和活化的EOS以及外周血CD₄⁺T淋巴细胞减少,能降低气道平滑肌张力,减轻气道高反应性,有利于预防哮喘复发。     

支气管哮喘豚鼠BALF炎症细胞中PPARγ、Nrf2和γ-GCS-h表达的变化

目的:研究支气管哮喘急性发作豚鼠肺泡灌洗液(BALF)炎症细胞中PPARγ、Nrf2和γ-GCS-h表达变化并探索PPARγ对Nrf2/γ-GCS-h作用。方法:40只健康雄性豚鼠随机化原则分成对照组(A组)、哮喘组(B组)、地塞米松组(C组)和罗格列酮组(D组),每组10只豚鼠,卵蛋白致敏法复制哮喘模型。收集BALF,行细胞计数和分类,离心,上清液行活性氧(ROS)和丙二醛(MDA)浓度测定,细胞涂片原位杂交检测PPARγ、Nrf2和γ-GCS-hmRNA表达,细胞涂片免疫细胞化学检测PPARγ、Nrf2和γ-GCS-h蛋白表达。结果:B组嗜酸性粒细胞数(EOS)比例高于A组、C组和D组,差异显著(P0.01),BALF中ROS和MDA浓度在B组中最高,4组间差异显著(均P0.05);PPARγ、Nrf2和γ-GCS-hmRNA和蛋白在B组表达最低,4组表达差异显著(均P0.01)。PPARγ与Nrf2/γ-GCS-h表达均呈正相关(均P0.05);γ-GCS-h与Nrf2表达呈正相关(r=0.954,P0.05);哮喘组PPARγ、γ-GCS-h和Nrf2表达均与浸润的嗜酸性粒细胞数呈负相关(均P0.05)。结论:PPARγ和Nrf2/γ-GCS-h在卵蛋白致敏急性支气管哮喘模型BALF炎症细胞中表达均下降;PPARγ可上调Nrf2/γ-GCS-h表达,在抑制炎症反应和氧化应激中发挥重要作用,这可能为支气管哮喘防治开辟新途径。     

低压缺氧复合NaCN中毒对大鼠呼吸频率及BALF成份的影响

目的研究低压缺氧复合氰化钠(NaCN)中毒对大鼠呼吸频率及支气管肺泡灌洗液(BALF)细胞数和总蛋白(TP)含量的影响。方法SD大鼠84只,随机分为常压常氧和低压缺氧2组。常压常氧组动物于重庆地区常规实验室内进行实验。将低压缺氧组动物置低压舱61 kPa环境放置72 h后开始实验。以3.6 mg/kg氰化钠皮下注射染毒,用RM6240型多道生理信号采集处理系统记录呼吸频率。制备BALF,测定BALF中细胞数,Lowery法测TP含量。结果低压缺氧致动物呼吸频率加快,但无统计学意义。BALF中细胞数和TP含量显著升高。低压缺氧动物NaCN中毒后呼吸频率及BALF中细胞数和TP含量进一步升高,均有显著性差异。结论低压缺氧加重NaCN中毒对大鼠呼吸系统的损伤作用。     

Allergen-induced late bronchoconstriction and airway hyperresponsiveness in guinea pigs

Allergen-induced bronchoconstrictive responses were examined in a guinea pig model actively sensitized by the inhalation of aerosolized ovalbumin (OA), which showed reproducible late bronchial responses (LBR). OA-challenge was performed under cover of mepyramine through the inhaled route in spontaneous breathing without anesthesia. The respiratory resistance (Rrs) was measured by the oscillation method for 96 h after OA challenge. All of the 22 guinea pigs displayed immediate bronchial responses (IBR), followed by 2 or 3 phase LBR that peaked at 6-8 h and 24 h after OA challenge. Examination of bronchoalveolar lavage fluid (BALF) revealed a significant increase in neutrophils at 1 h (p less than 0.01) and eosinophils at 7 h and 96 h (each p less than 0.01) after OA challenge. OA-challenge induced airway hyperresponsiveness to histamine (p less than 0.01) at 96 h that was associated with a significant increase in eosinophils (p less than 0.01) in BALF compared with lavages at 7 h. Intravenous administration of 1% OA induced a significant increase of leukotriene (LT)B4, C4, D4 in tracheal lavage fluids at IBR phase in each control (p less than 0.01). The increases of Rrs in LBR were inhibited almost completely by the pretreatment of KC-404, which is reported to have antagonistic action against LTC4/D4. These results suggest that allergen-induced late broncho-constrictions accompanied by airway hyperresponsiveness in guinea pigs are associated with the extensive infiltration into the airway lumen of inflammatory cells, and are concerned with the release of LTs. We also suggest that this LBR guinea pig model is useful in studying the mechanisms of the occurrence of LAR in humans, and in evaluating the action of anti-allergic drugs in LAR.     

The interaction of tumour necrosis factor alpha and endothelin-1 in pathogenetic models of asthma

Background There is evidence that tumour necrosis factor alpha (TNFα) may be an important mediator in initiating asthmatic airway inflammation. It has been proposed that endothelin-1 (ET-1) is involved in bronchoconstriction and airway remodelling in asthma. It is not known, however, if there is any interaction between TNFα and ET in perpetuating airway inflammation in asthma. Objective The present study aimed to determine the activities of ET-1 and TNFα in ovalbumin-sensitized guinea pigs and their roles in the development of airway inflammation. Method Twelve guinea pigs were sensitized by ovalbumin injection and aerosol inhalation. ET-1 levels were measured in both bronchoalveolar lavage fluid (BALF) and plasma by ¹²⁵-labelled endothelin-1 (ET-1) radioimmunoassay. The TNFα activity released from alveolar macrophage (AM) in BALF was estimated by ELISA. Cultured bovine airway smooth muscle cells (BASMCs) were treated with TNFα (1000 units/5 ± 10⁴ cells) for different times. ET-1 levels in harvested medium from these cells were measured by radioimmunoassay. Cultured human fetal lung fibroblasts (HFLFs) were incubated with ET-1(10^–8–10^–6M), then ³HTdR incorporation to these cells and cell counting were performed. The effects of ET-1 stimulation on the granulocyte macrophage colony stimulating factor (GM CSF) gene expression in HFLFs were estimated by using RT- PCR method. Results ET-1 levels in both plasma and BALF were significantly higher in ovalbumin- sensitized guinea-pigs compared with those in controls (422.27 × 175.0pg/mL vs 277.311 × 88.0pg/mL, P < 0.05, 81.22 × 16.15 vs 49.81 × 12.64pg/mL, P < 0.05) while TNFα activity was also significantly increased in the OVA-sensitized group compared with that in the control group (6010 ± 1900pg/mL vs 2810 × 450 pg/mL, P < 0.05). The ET-1 level in harvested medium of BASMCs rose significantly in 12 h in the TNF-α treated group (from < 5pg/mL to53.72 × 14.3pg/mL, P < 0.001), and remained at a similar level for 24 h in the TNFα treated group. It was shown that ET-1 not only stimulated cell proliferation but also induced GM-CSF mRNA expression in HFLFs. Conclusion ET-1 levels in both plasma and BALF and TNFα release from macrophage are increased significantly in ovalbumin-sensitized guinea-pigs. TNFα stimulates ET-1 secretion from cultured BASMCsw; ET-1 accelerates cell proliferation and induces GM- CSF mRNA expression in the human fetal lung fibroblast.     

哮喘豚鼠内皮素、心钠素含量的变化及心钠素对内皮素含量的影响

目的:探讨内皮素-1(ET-1)在哮喘发病中的可能作用及心钠素(ANF)对ET-1水平的影响。方法:采用放免法测定各组豚鼠支气管肺泡灌洗液(BALF)和血浆ET-1、ANF、cGMP含量。结果:哮喘组豚鼠血浆及BALF中ET-1、ANF、cGMP均显著高于对照组;哮喘组豚鼠血浆中ANF与ET-1含量呈显著负相关(r=-0.638,P<0.05);BALF中ET-1与ANF含量呈高度负相关(r=-0.921,P<0.01)。哮喘组豚鼠血浆中ANF与cGMP含量呈显著正相关(r=0.848,P<0.01),BALF中ANF与cGMP含量呈显著正相关(r=0.831,P<0.01)。哮喘+重组大鼠ANF(rANF)组豚鼠停止输注rANF后30min,血浆及BALF中ET-1水平均明显低于哮喘组。cGMP水平显著高于哮喘组。结论:ET-1在哮喘的发病中可能有重要作用,ANF抑制ET-1合成及分泌。     

NGF在哮喘豚鼠支气管肺泡灌洗液细胞中的表达

为了通过对神经生长因子和支气管肺泡灌洗液细胞在哮喘发病中的作用的研究进而探讨哮喘的神经免疫调节机制 ,本研究应用免疫组织化学方法研究了哮喘豚鼠支气管肺泡灌洗液细胞中神经生长因子的表达变化。结果发现 ,哮喘豚鼠神经生长因子阳性嗜酸细胞和淋巴细胞百分率明显增加 ( P<0 .0 1,P<0 .0 5 ) ;肺泡巨噬细胞绝对数量增加 ,神经生长因子表达也明显上调 ( P<0 .0 1) ,且呈 NGF阳性反应的小型肺泡巨噬细胞数量大大多于大型肺泡巨噬细胞。提示 ,气道炎症细胞内的神经生长因子可能参与哮喘发病的病理生理过程     

慢性低压低氧对大鼠肺组织HIF-1ɑ、COX1蛋白及氧化应激反应的影响

目的探讨慢性低压低氧环境对大鼠肺组织细胞色素C氧化酶1(COX1)蛋白及氧化应激反应的影响。方法将大鼠随机分为常氧组(1 500 m)和低氧组(4 300 m),低氧组大鼠暴露低氧30 d后采集标本。用Western blot检测肺组织COX1蛋白的表达及ELISA检测肺组织和血清HIF-1ɑ、血浆ROS、肺组织SOD和CAT酶。用生理信号采集系统测定肺动脉压(PAP)。结果在低氧组的大鼠血清和肺组织内HIF-1α蛋白显著高于常氧组(P0.01);ROS含量显著低于常氧组(P0.01);COX1蛋白在低氧组的大鼠肺组织中表达显著下降(P0.01);血清总抗氧化能力升高(P0.01)。结论高海拔对机体的影响可能是直接性的损伤,而并非仅仅是氧化应激反应所致。     

Nrf2在支气管哮喘豚鼠炎症细胞中调控γ-谷氨酰半胱氨酸合成酶的表达

目的：探讨核因子相关因子-2(Nrf2)调控γ-谷氨酰半胱氨酸合成酶(γ-GCS)在支气管哮喘豚鼠肺泡灌洗液(BALF)炎症细胞中的表达。方法：38只健康雄性豚鼠随机分为对照组（A组）、哮喘组（B组）和地塞米松治疗组（C组），卵蛋白致敏法复制哮喘模型，检测3组豚鼠肺组织匀浆中丙二醛（MDA）浓度，收集BALF，行细胞计数和分类。离心，细胞涂片行免疫细胞化学和原位杂交，检测Nrf2、Bach1、γ-GCS蛋白和mRNA。结果：（1）B组嗜酸性粒细胞数（EOS）比例高于A组和C组；（2）肺组织中MDA浓度B组高于A组和C组；（3）γ-GCS原位杂交A组A值高于B组和C组；Nrf2、Bach1原位杂交A值3组差异无显著；（4）γ-GCS 免疫细胞化学B组A值低于A组；Nrf2细胞核内阳性率 B组低于A组和C组；Bach1细胞核内阳性率B组高于A组和C组；（5）γ-GCS mRNA表达（A值）与Nrf2核内阳性率呈正相关，与Bach1核内阳性率呈负相关；B组BALF 中γ-GCS mRNA表达（A值）与EOS比例呈负相关。结论：支气管哮喘豚鼠体内存在氧化/抗氧化失衡，炎症反应使γ-GCS在豚鼠支气管哮喘炎症细胞中的表达降低，地塞米松可以通过调节Nrf2/Bach1核转位而增加γ-GCS表达。     

Decrease of subcutaneous adipose tissue lipolysis after exposure to hypoxia during a simulated ascent of Mt Everest

The purpose of this study was to examine the effects of prolonged hypoxia on adipose tissue lipolysis, in relation to the weight loss usually observed at high altitude. Eight male subjects were exposed for 31 days to gradually increasing hypobaric hypoxia up to the equivalent altitude of 8848 m (Mt Everest) in a decompression chamber, after 7 days at 4350 m for altitude pre-acclimatization. A biopsy of subcutaneous adipose tissue was performed before and after hypoxic exposure, to study in vitro changes in adipose tissue sensitivity. Fat mass, adipocyte volume and spontaneous lipolysis were not impaired by the exposure to hypoxia. The in vitro lipolytic response to epinephrine, isoproterenol, growth hormone (GH) and parathormone (PTH) decreased significantly (P<0.01, P<0.05, P<0.01 and P<0.01 respectively), as did the plasma concentration of free fatty acid (P<0.01). The anti-lipolytic effect promoted by alpha2-adrenergic receptor stimulation (epinephrine with propranolol) was greater after hypoxia (P<0.05), while the anti-lipolytic activity of insulin was decreased (P<0.01). In conclusion, prolonged exposure to hypobaric hypoxia led to a potent reduction in lipid mobilization, through a decrease in the efficiency of beta-adrenergic, GH and PTH lipolytic pathways, as well as an increment in the alpha2-adrenergic-receptor-mediated anti-lipolytic effects.