支气管哮喘患者外周血白细胞糖皮质激素受体的改变

应用放射配体结合法和放射免疫法分别检测了１７例哮喘患发作期外周血白细胞糖皮质激素受体（ＧＲ）和血浆皮质醇（Ｆ）。结果：外周血白细胞ＧＲ最大结合容量（Ｒ０）为１２９０８±２５０１位点／细胞，与健康对照组比较无显差异（Ｐ＞０．０５）。ＧＲ平衡解离常数（Ｋｄ）为１６．５４±５．３６ｎｍｏｌ／Ｌ，明显高于对照组（Ｐ＜０．０１）。血浆Ｆ为４３２±２７５ｎｍｏｌ／Ｌ，与对照组比较无显差异（Ｐ＞０．０５）     

支气管哮喘和糖皮质激素受体关系的研究进展

支气管哮喘(bronchial asthma)是一种常见的慢性非特异性炎症性疾病,糖皮质激素(glucocorticoid,GC)是目前治疗哮喘的首选抗炎药,使对糖皮质激素作用分子机制的研究越来越广泛。糖皮质激素(GC)与糖皮     

支气管哮喘患者外周血白细胞中糖皮质激素受体的研究

采用３Ｈ－Ｄｅｘ放射配体结合分析法测定２２例正常人及２０例哮喘患者在糖皮质激素（ＧＣ）治疗前后外周血白细胞中糖皮质激素受体（ＧＣＲ）水平。结果：哮喘患者外周血白细胞ＧＣＲ（３９６６±１１０９位点／细胞）明显低于健康正常人（５２５４±１２８９位点／细胞）（Ｐ＜０．０５）；哮喘患者经ＧＣ治疗一周后，其白细胞中ＧＣＲ（２０９１±４９４）明显低于治疗前（Ｐ＜０．０５）；但哮喘患者ＧＣ敏感组白细胞中ＧＣＲ与ＧＣ耐受组之间无显著差异（Ｐ＞０．０５），并对其发生机制作了初步探讨     

吸入激素对哮喘患者糖皮质激素受体的影响

应用放射配基结合分析法,检测了哮喘患者未用激素、吸人激素时的外周血单个核白细胞(MNL)糖皮质激素受体(GR)水平,结果发现哮喘患者未用激素组MNL之GR明显低于正常人(P<0.05),吸人激素组MNL之GR虽低于未用激素组,但无显著性差异(P>0.05)。结果表明哮喘患者GR降低,而在吸人激素后GR无明显变化。     

糖皮质激素对支气管哮喘患者血清干细胞因子表达的影响

目的检测干细胞因子（stem cell factor,SCF）在哮喘患者糖皮质激素治疗前后血清中的含量,评价糖皮质激素对SCF在支气管哮喘中的影响及意义。方法选择2009年3月～2010年4月入住我院呼吸科的支气管哮喘急性发作期患者33例作为研究对象,使用糖皮质激素进行治疗,采用酶联免疫吸附试验（ELISA）检测其治疗前后的血清SCF水平,同时测定25例正常对照血清SCF水平。结果糖皮质激素治疗后患者血清中SCF的含量较对照组明显增高（P〈0.05）;治疗后患者血清中SCF的含量显著低于治疗前水平（P〈0.05）;治疗缓解后患者血清中SCF的含量与对照组比较差异无统计学意义（P〉0.05）。结论糖皮质激素治疗可降低SCF的表达,SCF在哮喘发病及病情判断中可能起重要作用。     

糖皮质激素对哮喘患者血清和诱导痰中干细胞因子表达的影响

目的检测SCF蛋白在哮喘患者糖皮质激素治疗前后血清和诱导痰中的含量,评价糖皮质激素对SCF在支气管哮喘中的影响及意义。方法对32例哮喘患者用糖皮质激素进行治疗,应用ELISA方法测定糖皮质激素治疗前后血清以及诱导痰中SCF蛋白含量。结果糖皮质激素治疗前的哮喘患者与正常健康者比较,血清以及诱导痰中SCF蛋白明显升高,具有显著性差异(P<0.05)。糖皮质激素治疗后,血清以及诱导痰中SCF蛋白比治疗前的哮喘患者明显降低,与正常对照组比较无显著性差异(P>0.05)。结论结果显示SCF在血清以及诱导痰中均有表达,哮喘发作时含量明显增高。糖皮质激素治疗可降低SCF的表达,提示SCF与哮喘疾病紧密相关。     

Graves眼病外周血单核细胞糖皮质激素受体表达类型

OBJECTIVE: To study the expression of glucocorticoid receptor (GR) isoform in the peripheral blood mononuclear cell (PBMC) of patients with Graves' ophthalmopathy (GO). METHODS: Semi-quantitative RT-PCR was used to analyze RNA isolated from PBMC of the patients with GO and the normal volunteers. The level of plasma total cortisol (PTC) at 8 a.m. was measured. RESULTS: The hGR alpha/GR beta mRNA ratios of the two groups were 7.58 +/- 5.42 and 14.65 +/- 8.30, respectively. There was significant difference between the two groups (P < 0.05). The PTC levels of the two groups were 304.23 +/- 92.06 and 313.73 +/- 111.05, and no significant difference between them was noted (P > 0.05). No correlation was found between hGR alpha/GR beta mRNA and PTC levels. CONCLUSION: hGR alpha/GR beta mRNA may play a role in the pathogeny of Graves' ophthalmopathy.     

支气管哮喘与糖皮质激素受体基因多态性的关系

支气管哮喘是由多种细胞及细胞组分参与的呼吸道慢性非特异性炎症,肾上腺糖皮质激素抗炎治疗已成为哮喘现代治疗的主要方法。但有少数患者对激素治疗的敏感性低而称为"激素抵抗性哮喘"。激素抵抗的机制还不是十分清楚,基于糖皮质激素需要通过糖皮质激素受体来发挥生物学效应的机制,激素抵抗可能与GR基因多态性导致的GR结构和功能异常有关。     

Graves眼病外周血单核细胞糖皮质激素受体表达类型

目的　研究甲状腺功能正常型 Graves眼病患者外周血单核细胞糖皮质激素受体表达类型变化。方法　用半定量 RT- PCR方法检测患者及正常对照组外周血单个核细胞 h GRα/ GRβm RNA比值 ,同时检测两组晨 8:0 0血浆总皮质醇水平。结果　两组的 h GRα/ GRβ m RNA比值分别为 7.5 8± 5 .42和 14.6 5± 8.30 ,两组间比较有统计学差异 (P<0 .0 5 ) ;皮质醇分别为 30 4.2 3± 92 .0 6和 313.73± 111.0 5 ,两组间比较无统计学差异 (P<0 .0 5 )。h GRα/ GRβ m RNA与血浆总皮质醇水平之间无相关关系。结论　 h GRα/ GRβ m RNA可能在 Graves眼病发病中起着一定作用     

受体功能与临床研究

受体功能与临床研究糖皮质激素受体糖皮质激素受体（ｇｌｕｃｏｃｏｒｔｉｃｏｉｄｒｅｃｅｐｔｏｒ，ＧＲ）是甾体激素受体超家族的一个成员，这超家族除了所有的甾体激素的受体之外，还包括甲状腺激素受体，视黄酸受体以及一些配体尚未被发现的受体（通称为孤儿受体ｏｒ...     

Changes of glucocorticoid receptors in peripheral leukocytes in patients with bronchial asthma

ＣｈａｎｇｅｓｏｆｇｌｕｃｏｃｏｒｔｉｃｏｉｄｒｅｃｅｐｔｏｒｓｉｎｐｅｒｉｐｈｅｒａｌｌｅｕｋｏｃｙｔｅｓｉｎｐａｔｉｅｎｔｓｗｉｔｈｂｒｏｎｃｈｉａｌａｓｔｈｍａＺｈａｎｇＨａｉｂｏ（张海波）；ＬｕｏＷｅｎｔｏｎｇ｀（罗文侗）；ＬｉｕＺｈｉｍｉｎ...     

补肾平喘膏方对支气管哮喘大鼠肺组织糖皮质激素受体的影响

目的：观察支气管哮喘大鼠肺组织中糖皮质激素受体（glucocorticoid receptor,GR）的变化情况以及补肾平喘膏方对其的影响,以探讨补肾平喘膏方防治支气管哮喘的作用机制。方法：60只SD大鼠随机分为正常对照组、模型组、地塞米松组、膏方预防组、膏方治疗组和膏方防治（预防加治疗）组,每组10只。除正常对照组外,各组大鼠以卵白蛋白致敏并诱发哮喘模型。采用地塞米松或膏方治疗后,HE染色法检测大鼠肺组织病理学改变,免疫组织化学法检测肺组织中GR的表达情况。结果：模型组肺组织GR表达低于正常对照组（P〈0.05）,膏方预防组、治疗组、防治组肺组织GR的表达较模型组明显上调（P〈0.05）,与正常对照组比较,差异无统计学意义（P〉0.05）。其中膏方预防组GR的表达显著上升（P〈0.01）,膏方各组与地塞米松组相比亦明显上升（P〈0.01）。结论：补肾平喘膏方可能通过上调哮喘大鼠肺组织中GR的水平治疗哮喘。     

参麦对哮喘大鼠肺组织糖皮质激素受体的影响

目的 观察参麦对哮喘大鼠的治疗作用以及对肺组织中糖皮质激素受体(GR)表达的影响.方法 30只SD大鼠随机分为对照组、哮喘组、激素组、参麦低剂量组、参麦高剂量组,每组6只.除对照组外,各组大鼠以卵蛋白致敏并诱发哮喘.哮喘组注射0.9%生理盐水2 mL激素组注射地塞米松0.5 mg/kg,参麦组注射地塞米松0.5 mg/kg加参麦注射液(低剂量组1 mL,高剂量组2 mL),用药14 d.比较各组肺泡灌洗液(BALF)中嗜酸性粒细胞比例(Eos%)和细胞因子水平[白细胞介素-4(IL-4)、γ干扰素(IFN-γ)],用qRT-PCR检测肺组织中的GR mRNA,用Western blot印迹法检测肺组织中GR蛋白的表达.结果 哮喘组BALF中Eos%显著高于对照组、激素组、参麦高、低剂量组(P<0.001).参麦高剂量组BALF中Eos%显著低于激素组(P<0.05).哮喘组BALF中IFN-γ低于对照组、激素组、参麦高、低剂量组(P<0.01),IL-4高于对照组、激素组、参麦高、低剂量组(P<0.05).参麦高剂量组BALF中IFN-γ高于激素组(P<0.05),IL-4低于激素组(P<0.05).激素组肺组织GR mRNA表达低于对照组(P<0.05),参麦高剂量组肺组织中GR mRNA表达高于激素组(P<0.05).参麦高剂量组肺组织中GR蛋白表达显著高于哮喘组和激素组(P<0.05).结论 参麦能上调哮喘大鼠肺组织中的GR mRNA和GR蛋白的水平,这可能是参麦治疗哮喘的主要机制.     

Impact of psychosocial stress on airway inflammation and its mechanism in a murine model of allergic asthma

Background  It has already been recognized that psychosocial stress evokes asthma exacerbation; however, the mechanism of how stress gets inside the body is not clear. This study aimed to observe the impact of psychosocial stress on airway inflammation and its mechanism in the ovalbumin-induced asthmatic mice combined with social disruption stress.

Methods  Thirty-six male BALB/c mice were randomly divided into: control group, asthma group (ovalbumin-induced), asthma plus social disruption stress group (SDR), and SDR group. The open field video tracking system was used to assess animal behaviors. The invasive pulmonary resistance (RL) and dynamic lung compliance (cdyn) test system from Buxco was applied to detect pulmonary function. The enzyme-linked immunosorbent assay (ELISA) was utilized to determine OVA-IgE, T-helper type 2 (Th2) cytokines (IL-4, IL-5, IL-13) and corticosterone in mouse serum, the Th2 cytokines (IL-4, IL-5, IL-13, IL-6, TNF-α) in bronchoalveolar lavage fluid (BALF), and IL-6 and TNF-α levels in the supernatant of splenocytes cultured in vitro. Hematoxylin-eosin (H&E) staining was used to assess airway inflammation in lung histology. The cell count kit-8 assay (CCK-8) was applied to evaluate the inhibitory effect of corticosterone on splenocyte proliferation induced by lipopolysaccharide (LPS). Real time-PCR and Western blotting were utilized to determine glucocorticoid receptor (GR) mRNA and GR protein expression in lungs.

Results  The open field test showed that combined allergen exposure and repeated stress significantly shortened the time the mice spent in the center of the open field (P <0.01), increased ambulatory activity (P <0.01) and the count of fecal boli (P <0.01), but deceased vertical activity (P <0.01). Results from pulmonary function demonstrated that airway hyperresponsiveness (AHR) was enhanced by psychosocial stress compared with allergy exposure alone. The ELISA results showed that cytokines in serum and BALF were significantly increased (P <0.05). Moreover, the lung histology showed that infiltrated inflammatory cells were significantly increased in the asthma-SDR group compared with the asthma group (P <0.05). Interestingly, serum corticosterone was remarkably raised by psychosocial stress (P <0.05). In addition, the inhibitory effect of corticosterone on IL-6 and TNF-α in LPS-stimulated splenocyte cultures in vitro was diminished in the asthma-SDR group compared to the asthma group. The CCK-8 test revealed that the inhibition effect of corticosterone on splenocyte proliferation induced by LPS was significantly impaired in the SDR and asthma-SDR groups, while no significant effect was observed in the control and asthma groups. Furthermore, expression of GR mRNA and GR protein were significantly reduced in the lung tissues of the asthma-SDR group (P <0.05).

Conclusions  Social disruption stress can promote anxiety behavior, activate the hypothalamic-pituitary-adrenal (HPA) axis, increase AHR and inflammation, and also impair glucocorticoid sensitivity and its function in a murine model of asthma. The down-regulation of GR expression induced by social disruption stress is in part associated with glucocorticoid insensitivity, which leads to asthma exacerbation.

     

多发性骨髓瘤患者外周血白细胞糖皮质激素受体的变化

探讨多发性骨髓瘤外周血白细胞糖睦质激素受体表达水平与糖皮质激素疗效着关系。应用放射配体结合一点分析法检测了２３例ＭＭ和１０例正常对照外周血白细胞ＧＲ表达水平。ＭＭＧＲ水平，初诊未化疗组位点／细胞，部分缓解组位点／细胞，与正常对照组比较均无显著差异。难治性ＭＭ组位点／细胞，明显低于其他组。ＭＭ患者外周血白细胞ＧＴ检测有助于预测糖皮质激素疗效。     

布地奈德对大鼠哮喘肺组织Toll样受体4和5表达的调控作用

目的: 观察布地奈德对哮喘大鼠肺组织中Toll样受体4(TLR4)和TLR5表达的影响, 探讨TLRs在哮喘炎症机制中的作用。方法: 采用哮喘大鼠模型, 随机分成哮喘组、对照组和布地奈德组,免疫组织化学法检测肺组织TLR4和TLR5的表达。结果:哮喘组( 0.1960.045 OD值)肺组织TLR4的光密度值与对照组(0.1720.025 OD值)差异无统计学意义(P>0.05);布地奈德组( 0.1380.026 OD值)均显著低于对照组和哮喘组 (均P<0.05)。哮喘组(0.1850.029 OD值)肺组织TLR5的光密度值显著高于对照组(0.1380.014 OD值)(P<0.05);布地奈德组(0.1520.024 OD值)与对照组及哮喘组差异均无统计学意义(均P>0.05)。肺组织TLR4和TLR5蛋白的表达水平无显著相关性( n = 26, r =0.246,P> 0.05)。结论: OVA致敏的哮喘大鼠肺组织TLR5的表达升高,TLR4没有变化,TLR5在哮喘的炎症中可能起了促炎作用。布地奈德能下调TLR4和TLR5的表达,其抗炎作用可能通过下调TLR4和TLR5的途径。     

Studies on the function and regulation of low－affinity glucocorticoid receptor

Ｓｔｕｄｉｅｓｏｎｔｈｅｆｕｎｃｔｉｏｎａｎｄｒｅｇｕｌａｔｉｏｎｏｆｌｏｗ－ａｆｆｉｎｉｔｙｇｌｕｃｏｃｏｒｔｉｃｏｉｄｒｅｃｅｐｔｏｒ￥ＬｅＹｉｎｇｙｉｎｇ（乐颖影）；ＸｕＲｅｎｂａｏ（徐仁宝）（ＤｅｐａｒｔｍｅｎｔｏｆＰａｔｈｏｐｈｙｓｉｏｌｏ...     

白三烯及其受体与哮喘的关系

半胱氨酰白三烯(cysLTs)是哮喘发病过程中最重要的炎症介质之一,白三烯(LTs)是花生四烯酸经5-脂氧酶代谢途径形成的代谢产物,包括LTC4、LTD4和LTE4,具有众多的生物学活性,通过特异的细胞表面受体发挥作用.LTs促使炎症细胞在气道的聚集,诱发气道平滑肌收缩,增加气道高反应性,促进气道上皮细胞、平滑肌细胞增殖,揭示cys-LTs在气道重塑的发生、发展中起重要作用.     

甘草酸二铵上调急性肺损伤大鼠糖皮质激素受体的表达

目的观察甘草酸二铵(DG)对急性肺损伤(ALI)大鼠肺组织糖皮质激素受体(GR)及血清肿瘤坏死因子-α(TNF-α)、白细胞介素-10(IL-10)表达的影响。方法将36只雄性SD大鼠随机分为假手术组(S组)、ALI组、DG干预组(HLG组)、地塞米松干预组(HLD组)、ALI受体阻断组(ALIR组)和DG干预受体阻断组(HLGR组)。各组动物造成失血性休克,然后给予内毒素(LPS)2mg/kg腹腔注射;LPS注射前1h,分别给予DG 20mg/kg或地塞米松2mg/kg腹腔注射,ALIR组和HLGR组大鼠肌肉注射受体阻断剂RU486。测定大鼠肺湿干比(W/D)、血氧分压(PaO2),并检测肺组织GR mRNA及GR蛋白的表达,同时测定血清TNF-α、IL-10浓度。结果 (1)ALI组TNF-α明显高于S组、HLGR组和HLG组(P<0.01);ALI组IL-10明显高于S组(P<0.01),但低于HLG组和HLGR组(P<0.05)。(2)ALI组GR mRNA和蛋白的表达明显低于S组(P<0.01);HLG组GRmRNA和蛋白的表达则明显高于ALI组(P<0.05,P<0.01)。(3)ALI组肺组织出现充血、水肿、中性粒细胞浸润,HLG组肺部炎症较ALI组减轻。结论 DG可能通过上调GR及IL-10的表达,同时抑制TNF-α的过度表达,从而起到减轻ALI的作用。