生脉散组分配伍对热损伤大鼠糖皮质激素受体的影响

目的：研究生脉散组分配伍对热损伤大鼠糖皮质激素受体（glucocorticoid receptor,GR）的影响。 方法：雄性SD大鼠32只随机分为正常对照组、模型组、人参总皂苷组和生脉散组分配伍组（简称组分配伍组）,每组8只,连续灌胃1周进行预处理。除正常对照组外,其余各组大鼠于末次给药30min后复制大昂热损伤模型。随后立即断头处死动物,收集血清和肝、肺、肾脏组织。酶联免疫吸附测定法（enzyme-linked immkinosorbent assay,ELISA）检测血清皮质酮（corticosterone,CS）的浓度,放射免疫检测法（radioimmunoassay,RIA）检测血清促肾上腺皮质激素（adrenocorticotropic hormone,ACTH）的浓度;放射性配体受体结合法（radioligand receptor binding assay,RRA）检测肝、肺、肾细胞液GR结合容量。 结果：模型组肝、肺、肾胞液GR明显低于正常对照组（P〈0.01）。组分配伍组肝和肺胞液GR结合容量明显高于模型组（P〈0．01）,肾胞液GR结合容量与模型组比较,差异无统计学意义。组分配伍组肝胞液GR明显高于人参总皂苷组（P〈0．01）,肺和肾胞液GR结合容量与人参总皂苷组比较有上升的趋势．但差异无统计学意义。正常大鼠CS及ACTH水平与模型组、组分配伍组和人参总皂苷组比较,差异有统计学意义（P〈0．01）,模型组CS及ACTH水平与各给药组比较,差异无统计学意义。 结论：生脉散组分配伍可增强人参总皂苷上调热损伤大鼠GR水平的作用。     

参附汤对失血性休克大鼠糖皮质激素及其受体的影响

深入探讨参附汤的药理作用机理。以急性失血性休克大鼠为实验对象，同步观察参附汤对血浆皮质酮及肝胞液，胸腺细胞糖皮质激素受体的影响。参附汤组大鼠肝胞液及胸腺细胞ＧＲ的结合位点都明显高于单纯失血组，参附汤组血浆皮质酮略高于失血组。参附汤可纠正失血性休克模型的ＧＲ的减少，以发挥其救治休克，回阳固脱的作用。     

GRβ对肾小球系膜细胞糖皮质激素效应的影响

目的:构建糖皮质激素受体β(GRβ)不同表达水平的肾小球系膜细胞株,研究GRβ对肾小球系膜细胞糖皮质激素效应的影响.方法:利用逆转录病毒载体pLXSN将重组GRβ正义和反义基因转入肾小球系膜细胞,经细胞培养、逆转录聚合酶链反应、基因测序和蛋白质印迹分析鉴定所构建的细胞株,应用MTT法和流式细胞术检测细胞内不同表达水平的GRβ对地塞米松的细胞增殖抑制效应和细胞周期变化的影响.结果:构建的肾小球系膜细胞分别有正确的GRβ正义和反义基因整合,转染了GRβ正义基因的肾小球系膜细胞内GRβ蛋白质表达水平明显高于转染了GRβ反义基因者(109.74±10.63 vs.19.08±1.01,P＜0.05);地塞米松对GRβ高表达的肾小球系膜细胞的增殖抑制效率显著低于GRβ低表达的肾小球系膜细胞(18.47%±2.12% vs.60.33%±5.29%,P＜0.05).在地塞米松的抑制下,转染了正义GRβ基因的细胞中,其S期细胞降低程度和G1期细胞升高的程度均明显低于未转染的细胞.结论:肾小球系膜细胞内高表达的GRβ具有拮抗糖皮质激素效应的作用,细胞内GRβ表达水平是决定细胞对激素敏感或抵抗的重要因素.     

基于糖皮质激素受体信号通路中药抗抑郁作用及机制的研究进展

抑郁症发病机制复杂,其典型病理特征是糖皮质激素（GC）水平的异常升高和下丘脑-垂体-肾上腺（HPA）轴功能亢进,主要由GC受体（GR）介导。研究表明,由抑郁症患者GR功能降低和数量减少引起的HPA轴功能亢进是抑郁症的诱因之一。而抗抑郁药可以改善GR的异常变化,提示GR是抗抑郁的一个新靶点。近年来,中药在治疗抑郁症方面取得了很大进展,文章就中药基于GR途径治疗抑郁症的作用及机制进行综述,以期为临床治疗抑郁症提供参考。     

严重烧伤早期小鼠腹腔巨噬细胞糖皮质激素受体变化及安定-氯胺酮对其影响

目的观察严重创伤早期小鼠腹腔巨噬细胞糖皮质激素受体(GR)蛋白表达的变化,并探讨安定-氯胺酮对其变化的影响,为安定-氯胺酮在创伤应激中的作用提供可靠实验依据.方法 95只成年健康昆明小鼠,随机分为正常对照组、烧伤组、安定-氯胺酮处理组、烧伤后安定-氯胺酮处理组,应用Western blot技术检测各组小鼠处理后早期24h内不同时期腹腔巨噬细胞GR的蛋白表达水平.结果小鼠严重烧伤后30min,腹腔巨噬细胞中GR的表达就已经开始降低,在6h达到最低,显著低于正常对照组,12h时逐渐回升,但在24h时仍低于正常.而安定-氯胺酮组GR的表达水平无显著差异,在严重烧伤后应用安定-氯胺酮能明显地抑制GR蛋白表达水平的降低,烧伤后安定-氯胺酮处理组各时相点与正常对照组相比无显著差异.结论严重烧伤可引起小鼠腹腔巨噬细胞GR表达水平的下降,而单纯应用安定-氯胺酮对小鼠腹腔巨噬细胞GR的表达水平无明显影响,在严重烧伤后应用安定-氯胺酮能显著抑制GR水平的下调,故安定-氯胺酮可能部分改善小鼠严重烧伤诱发的应激状态.     

烧伤后小鼠血清皮质酮及肝组织糖皮质激素受体水平的变化

目的：探讨烧伤小鼠24h内肝组织糖皮质激素受体时相变化特点,方法：将60只BALB／c小鼠随机分为正常对照组和实验组，实验组造成背部Ⅲ度15％－20％烧伤，分别于伤后2，4，6，12，24h测定血清皮质酮浓度，采用Western blotting ,RT-CPR在蛋白和mRNA水平测定肝组织糖皮质激素受体。结果：烧伤小鼠血清皮质酮浓度4h达到高峰，24h仍未恢复正常；肝组织糖皮质激素受体在蛋白质水平明显降低4－6h降至最低，而mRNA水平仅仅在伤后2h有短暂降低，结论：烧伤应激引起小鼠血清皮质酮水平明显升高，其受体在蛋白及mRNA水平均可降低，但蛋白降低不主要发生在mRNA水平。     

糖皮质激素受体基因在受体缺失型哺乳动物细胞中的表达

本文在证实小鼠成纤维细胞系Ｅ８２．Ａ３无糖皮质激素受体（ＧＲ）的基础上，采用磷酸钙共沉淀法，用含大鼠肝ＧＲｃＤＮＡ的质粒ｐＲＧＲ－Ｎｅｏ转染给Ｅ８２．Ａ３细胞，并用Ｇ４１８筛选稳定表达细胞，Ｓｃａｔｃｈａｒｄ分析表明，转化细胞特异性结合［３Ｈ］曲安缩酮的结合参数及甾体特异性与经典ＧＲ相同，说明所筛选得的细胞确实表达了ＧＲ。     

Increased hsp70 of glucocorticoid receptor complex induced by scald and heat stress and its possible effect on the affinity of glucocorticoid receptor

Background Glucocorticoid （GC） insensitivity/GC resistance is an important etiological and prognostic factor in multiple diseases and pathophysiological processes such as scald, shock and asthma. The function of GC was mediated by glucocorticoid receptor （GR）. Scald not only decreased the expression of GR but also reduced the affinity of GR, which played an important role in GC resistance in scalded rats. Whereas the molecular mechanism responsible for the decrease of GR affinity resulted from scald remains unclear. Recent studies showed that the changes of heat shock proteins （hsp） especially hsp90 and hsp70 of GR heterocomplex were associated with GR low affinity in vitro. Methods The affinity of GR in hepatic cytosols and in the cytosols of SMMC-7721 cells were determined by radioligand binding assay and scatchard plot. GR heterocomplex in cytosols were captured by coimmunoprecipation and the levels of hsp90 and hsp70 of GR complex were detected by quantitative Western blotting. Results Similar with that of hepatic cytosol of scalded rats, a remarkable decrease of GR affinity was also found in the cytosol of heat stressed SMMC-7721 cells. The level of hsp70 of GR complex in hepatic cytosol of scalded rats （30% total body surface area immersion scald） and in cytosol of heat stressed human hepatocarcinoma cell line SMMC-7721 were both increased by 1.5 fold, whereas no change of hsp90 in GR heterocomplex was found. According to the correlation analysis, there may be a positive relationship between increased hsp70 of GR complex and decreased GR affinity in the cytosols. Conclusions The primary results indicated that the level of hsp70 of GR heterocomplex was increased in the hepatic cytosol of scalded rats and the cytosol of heat stressed SMMC-7721 cells. The increase of hsp70 of GR complex might be associated with the decrease of GR affinity.     

人参茎叶皂苷对失血性休克大鼠糖皮质激素受体的影响

目的 观察人参茎叶皂昔(ginsenosides，GSS)对失血性休克大鼠糖皮质激素受体(GR)的影响，并分析其作用机制，为研制及时抢救失血性休克患者的天然药物制剂提供实验依据。方法 雄性SD大鼠随机分为失血性休克组和对照组，失血性休克组分别每日ig200，100，50mg／kg GSS水溶液，对照组和模型组ig蒸馏水2mL，共10d。以[^3H]地塞米松为配体，用一点分析法测脑和肝胞液GR结合活性(Rs)、半定量RT—PCR方法测肝胞液GR mRNA水平、放免法测血浆促肾上腺皮质激素(ACTH)和皮质酮(GC)浓度。结果 GSS组大鼠脑和肝胞液的GR结合活性高于单纯失血性休克组，其中以中剂量组最明显(P＜0．01)；GSS组大鼠肝胞液GR mRNA表达水平高于单纯失血性休克组；GSS组大鼠血浆ACTH和GC浓度和单纯失血性休克组没有明显差别。结论 GSS可减轻失血性休克大鼠GR结合活性的下降幅度，作用机制可能与其促进了GR mRNA表达有关，并可能存在一个最佳剂量。     

糖皮质激素受体在多发伤后早期作用的研究

目的从组织细胞受体水平探讨糖皮质激素受体(GR)在多发伤中的作用。方法50例小鼠随机分成多发伤组(40例)和对照组(10例),建立多发伤小鼠动物模型。采用逆转录-聚合酶链反应(RT-PCR)法检测GRmRNA表达水平,同时检测血清丙氨酸转胺酶(ALT)、肌酐(Cr)水平,肺组织髓过氧化物酶(MPO)和小肠组织二胺氧化酶(DAO)活性。结果多发伤伤后6、24、72h的血、肝、肾、肺、小肠组织GRα表达明显降低,而GRβ明显高于对照组(P<0.05)。且多发伤组ALT、Cr和MPO升高,而DAO活性降低(P<0.05)。结论GR可能在多发伤早期器官组织的损伤与抗损伤机制方面起着重要作用。     

慢性阻塞性肺疾病激素不敏感与糖皮质激素受体核内转移的相关性

 目的  研究慢性阻塞性肺疾病 (chronic obstructive pulmonary disease,COPD)对糖皮质激素不敏感是否与糖皮质激素受体 (glucocorticoids receptor,GRα)的核内转移有关。方法  将来自12例健康人、15例轻中度哮喘患者和15例COPD患者的人外周血单个核细胞 (peripheral blood molecule cells,PBMC)进行体外培养。ELISA方法检测其IL-8蛋白质水平,并计算地塞米松 (Dex)半抑制浓度。PBMC在Dex中培养0.5~6 h,通过Western blot检测GRα蛋白质水平,GRα的核内转移则通过免疫荧光和共聚焦显微镜来观测和分析评估。结果  COPD患者PBMC较轻中度哮喘患者和健康志愿者对Dex相对不敏感。Dex半抑制率 (IC50Dex)与糖皮质激素受体GRα核内转移呈负相关 (r=-0.54,P=0.000 8)。Dex可诱导增加各组PBMC中的总GRα,但GRα胞内分布各组间存在差异。Dex可明显增加健康人及哮喘患者核内的GRα,但并未增加COPD患者核内GRα。健康人及哮喘患者的PBMC中,Dex预处理能显著抑制TNF-α诱导的IL-8分泌,而在COPD患者的PBMC中这种抑制作用不明显。结论  COPD对糖皮质激素的不敏感与GRα核内转移有关。GRα核内转移受抑制可能是造成糖皮质激素在COPD患者中发挥抑制炎性作用欠佳的原因之一。     

糖皮质激素受体的变化在救治急性呼吸窘迫综合征中的意义

根据急性呼吸窘迫综合征患者的糖皮质激素受体特异结合位点的变化，探讨在救治ＡＲＤＳ患者时糖皮质激素的合理使用方案。研究对象为综合性ＩＣＵ中２８例ＡＲＤＳ患者，采用放射配体结合法测定ＡＲＤＳ患者外周血白细胞ＧＲ特异结合位点。２８例ＡＲＤＳ患者均行机构能气。随机的１１例ＡＲＤＳ患者进行ＧＣ治疗干预。当ＧＲ结合位点减少〈５０％时，地塞米松按０．５ｍｇ‘ｋｇ＾－１．ｄ＾－１使用；当ＧＲ结合位点减少≥５０％时     

Effect of Dexamethasone on Expression of Glucocorticoid Receptor in Human Monocyte Cell Line THP-1

Glucocorticoid(GC)is one of the steroid hor-mones possessing anti-inflammatory and i mmuneinhibitory functions and has satisfactory effective-ness in controlling some chronic inflammation andi mmune diseases.But few patients are not sensi-tive to the therapy of massive-dose GC,named asGC resistance[1].GC exerts its biological effectsbybinding to a glucocorticoid receptor(GR).Twohuman isoforms of GR have been identified,termed GRαand GRβ.GRαis ubiquitously ex-pressed in al most all hu…     

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

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

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。     

Influence of drug treatment on glucocorticoid receptor levels in patients with coronary heart disease

Background Glucocorticoid signaling exerts major roles in inflammation, metabolism and depression, which are three crucial factors accompanying or underlying coronary heart disease. Although accumulating evidence indicates the influence of glucocorticoids on the pathology and treatment of coronary heart disease, there is still a dearth of pharmaceutical mechanisms for this relationship. This study aimed to investigate the influence of drug treatment on glucocorticoid receptor levels in coronary heart disease.Methods Eighty hospitalized patients (average age (59.0 7.5) years, 46 male and 34 female) with coronary heart disease were categorized into four groups with 20 members in each according to one of the four drugs they were treated with. The four drugs were: nitrated derivative isosorbide dinitrate, the beta-adrenergic receptor blocker metoprolol, the calcium antagonist nifedipine, and the HMG-CoA reductase inhibitor lovastatin. Glucocorticoid receptor protein levels of peripheral blood lymphocytes were tested using immunoblotting analysis before and after one month of treatment. Results Immunoblotting analysis showed increased glucocorticoid receptor levels after treatment with metoprolol and nifedipine. There were no statistically significant changes of glucocorticoid receptor levels after treatment with isosorbide dinitrate or lovastatin, although there were trends of up-regulation of glucocorticoid receptor expression after both treatments.Conclusions Both the beta-blocker and the calcium blocker can increase glucocorticoid receptor levels after chronic administration. This effect suggests a mechanism for their anti-inflammatory and other therapeutic roles for coronary heart disease and comorbid disorders.     

Influence of drug treatment on glucocorticoid receptor levels in patients with coronary heart disease

Background Glucocorticoid signaling exerts major roles in inflammation, metabolism and depression, which are three crucial factors accompanying or underlying coronary heart disease. Although accumulating evidence indicates the influence of glucocorticoids on the pathology and treatment of coronary heart disease, there is still a dearth of pharmaceutical mechanisms for this relationship. This study aimed to investigate the influence of drug treatment on glucocorticoid receptor levels in coronary heart disease.Methods Eighty hospitalized patients (average age (59.0 7.5) years, 46 male and 34 female) with coronary heart disease were categorized into four groups with 20 members in each according to one of the four drugs they were treated with. The four drugs were: nitrated derivative isosorbide dinitrate, the beta-adrenergic receptor blocker metoprolol, the calcium antagonist nifedipine, and the HMG-CoA reductase inhibitor lovastatin. Glucocorticoid receptor protein levels of peripheral blood lymphocytes were tested using immunoblotting analysis before and after one month of treatment. Results Immunoblotting analysis showed increased glucocorticoid receptor levels after treatment with metoprolol and nifedipine. There were no statistically significant changes of glucocorticoid receptor levels after treatment with isosorbide dinitrate or lovastatin, although there were trends of up-regulation of glucocorticoid receptor expression after both treatments.Conclusions Both the beta-blocker and the calcium blocker can increase glucocorticoid receptor levels after chronic administration. This effect suggests a mechanism for their anti-inflammatory and other therapeutic roles for coronary heart disease and comorbid disorders.     

Clinical Study on Effect of Chinese Herbal Medicine Combined with Hemodialysis in Treating Uremia

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