糖皮质激素受体基因多态性与骨密度关系的研究

目的 以体内糖皮质激素水平正常的人群为研究对象,研究糖皮质激素受体(GR)基因多态性与骨密度间的关系。方法 用特异的等位基因PCR方法检测人群的GR基因型,用DEXA检测腰椎、股骨各处骨密度。结果 在男性病例,各基因型间BMD的T值无明显统计学差异;在女性病例,各基因型间BMD的T值比例:TT型比CC型T值明显升高(P<0.05)。结论 GR基因外显子8的678位点突变(C→T),可使女性腰椎骨密度增加,具有骨密度保护作用。     

糖皮质激素联合特布他林治疗慢阻肺急性加重期的疗效研究

目的：分析糖皮质激素联合特布他林治疗慢阻肺急性加重期的疗效,并对患者进行疗效观察,探究其临床价值。方法方便选择长治医学院附属和平医院2014年3月―2015年7月收治的84例慢阻肺急性加重期患者,随机分成对照组和观察组,各42例,对照组采用特布他林治疗,观察组在对照组治疗的基础上,加入糖皮质激素。观察两组患者肺功能前后的变化。结果观察组患者肺功能(总有效率97.61%﹚明显高于对照组(总有效率88.09%﹚,差异具有统计学意义(P<0.05)。结论糖皮质激素联合特布他林治疗慢阻肺急性加重期的疗效明显。     

头部X线照射后大鼠血清中皮质酮含量和脾细胞中糖皮质激素受体变化及其相互关系的研究

给Wistar大鼠以10Gy X射线头部照射后不同时间测定血清皮质酮含量和脾细胞中糖皮质激素受体,结果表明:头照后24h受体数已降到对照组的25％,以后逐渐回升,至第9天恢复到接近正常水平。头照后受体的最大结合容量有降低趋势,但差异不显著,而Kd值显著增大,亲和力降低。皮质酮含量的变化呈双峰曲线,第1天即显著增高,至第9天仍显著增高,皮质酮含量和受体的变化规律不一致。体外实验还证实了1～10倍血清浓度的皮质酮在短时间内不会引起所测定的GCR改变。证明皮质酮的变化虽然可能是引起受体变化的一个原因,但不是主要原因。     

大豆苷元对糖皮质激素性骨质疏松大鼠骨量及骨微结构的影响

目的:观察大豆苷元对糖皮质激素性骨质疏松大鼠模型的骨密度(BMD)、骨矿含量(BMC)和骨微结构的影响,为临床预防及治疗糖皮质激素性骨质疏松提供实验依据。方法:将30只SD大鼠随机分为Control组(Con组,10只)、激素造模组(GCT组,10只)和激素造模同时大豆苷元干预组(DAI组,10只)。GCT组和DAI组分别给予泼尼松龙7.5mg/kg.d灌胃,Con组给予等量生理盐水。此外,DAI组每日给予DAI 5mg/kg灌胃。12周后,使用Micro-CT大鼠第4腰椎(L4)及大鼠左侧胫骨松质骨进行扫描。分析参数包括:骨矿含量(BMC);骨密度(BMD);骨小梁厚度(Tb.Th);骨小梁数量(Tb.N);骨小梁间隔(Tb.Sp);骨体积分数(BV/TV)。结果:(1)GCT组腰椎(L4)的BMD和BMC较Con组均显著降低,差异具有统计学意义(P<0.01),提示造模成功。DAI组腰椎(L4)BMD显著高于GCT组,差异具有统计学意义(P<0.05)。(2)GCT组左侧胫骨Tb.Th、Tb.N和BV/TV与Con组相比均显著降低,Tb.Sp显著增高,差异具有统计学意义(P<0.01)。DAI组Tb.Th、Tb.N、BV/TV较GCT组增高,其中Tb.Th、BV/TV显著增高,差异具有统计学意义(P<0.05),Tb.Sp显著降低,差异具有统计学意义(P<0.01)。结论:糖皮质激素可降低SD大鼠腰椎BMD和BMC,减少骨小梁数量,降低骨小梁厚度,组织骨密度和骨体积分数,增加骨小梁间隔。大豆苷元可以增加糖皮质激素诱导骨质疏松(GIOP)大鼠腰椎的BMD和BMC,可抑制糖皮质激素诱导的骨小梁数量减少,骨体积分数降低及骨小梁间隔增加,改善其骨微结构。大豆苷元对糖皮质激素所致的骨质疏松有治疗及预防作用。     

骨髓增生活跃的特殊类型全血细胞减少患者应用糖皮质激素疗效分析

目的 观察对骨髓增生活跃、网织红细胞计数＞1%、排除白血病等可引起全血细胞减少的疾病,及无足够证据诊断免疫相关性全血细胞减少和溶血性贫血的临床难于诊治的全血细胞减少患者给予应用糖皮质激素的早期疗效.方法 回顾分析12例符合上述条件患者应用糖皮质激素治疗的效果.结果 患者外周血白细胞、中性粒细胞绝对值、血红蛋白浓度有明显...     

软骨内成骨过程中影响胰岛素样生长因子-1表达的因素

软骨内成骨是人体生长、发育的重要生长方式,软骨内成骨异常会严重影响到青少年的健康成长以及中老年人的生活质量.生长激素/胰岛素样生长因子-1是软骨内成骨的中心轴,但多种因素可使其发生变化,从而导致软骨内成骨异常.本文总结了软骨内成骨过程中影响胰岛素样生长因子-1的因素,旨在为研究预防和治疗软骨内成骨异常提供指导.     

慢性淋巴细胞性甲状腺炎的局部免疫调节治疗

目的 评价局部免疫调节治疗对慢性淋巴细胞性甲状腺炎(CLT)患者的治疗效果和安全性.方法 选择81例CLT患者,采用甲状腺内局部注射糖皮质激素的方法,观察治疗前后患者自觉症状、甲状腺大小(B超测量)、甲状腺功能(TSH、FT3、FT4)和甲状腺过氧化酶抗体(TPoAb)等指标的变化.以患者的甲状腺功能正常或较前好转作为判定指标.结果 (1)总有效率为66%;(2)患者甲状腺左右叶分别从治疗前的(7.55±0.57)cm3和(6.57±0.49)cm3下降至治疗后的(6.84±0.45)cm3和(5.80±0.46)cm3(P＜0.05);(3)TPoAb从(338.2±43.2)mIU/L下降至(266.9±42.2)mIU/L(P＜0.01);(4)TSH、FT3、FT4治疗前分别为(19.56±2.90)μIU/L、(4.43±0.23)pmol/L、(14.40±1.32)pmol/L,治疗后分别为(7.44±1.62)μIU/L、(4.52±0.19)pmol/L、(14.82±0.75)pmol/L,TSH明显下降,有显著性差异;FT3、FT4有上升的趋势,但是无统计学意义;(5)治疗前后患者自觉症状明显好转.结论 局部免疫调节治疗CLT疗效确切、操作简便、安全价廉.     

Differentially modulated dendritic cells induce regulatory T cells with different characteristics

Dexamethason (DEX) treated DC display several features that establish them as candidates for specific allogeneic tolerance induction. We report the results of in vitro studies of polarization of the alloimmune T cell response with two types of differentially modulated human DC. Both DEX treated DC triggered by LPS for 6 h (DEX6-DC) and DEX treated DC triggered by LPS for 48 h (DEX48-DC) acquired low levels of costimulatory, adhesion, and MHC class II molecules compared with mature DC (mDC). In contrast to mDC, both DEX6-DC and DEX48-DC did not produce any IL-12. DEX6-DC were able to produce significant amounts of IL-10 whereas DEX48-DC did not actively produce IL-10. Conversely, the induction of IL-10 producing cells was significantly increased when PBL were stimulated with DEX48-DC compared with DEX6-DC. Both stimulation of PBL with DEX6-DC and DEX48-DC led to the induction of cell populations able to suppress the proliferative alloimmune response of primed T cells in a cell-cell contact independent and antigen-nonspecific manner. Tregs obtained after stimulation with DEX48-DC were also able to inhibit the IFN-gamma production of the effector cells and this effect could be blocked by anti-IL-10. Tregs induced by DEX6-DC produced similar amounts of IL-10, yet were not able to inhibit IFN-gamma production of the effector T cells, indicating a different mechanism. In summary, we show that differential modulation of DC results in the induction of different populations of regulatory T cells.     

Effect of hyperthermia and anoxia on glucocorticoid and mineralocorticoid receptor expression in neonatal rat hippocampus

Brief periods of neonatal asphyxia are frequently observed. Within the CNS, the hippocampus is known to be particularly vulnerable to the damaging effects of hypoxia/ischaemia. The hippocampus contains the highest concentration of both mineralocorticoid (MR) and glucocorticoid (GR) receptors and the balance between MR/GR activation influences cell birth and death. MR occupation appears to promote prosurvival actions, while GR overactivation favours neurodegeneration. It has been widely recognized that core body temperature is a critical determinant of the severity of hypoxic–ischemic brain injury; indeed, hyperthermia exacerbates the degree of damage. Therefore, the aim of the present investigation was to study the effect of elevated body temperature in newborn rats under control conditions or during neonatal exposure to a critical anoxia, on changes of MR and GR mRNA expression in the rat hippocampus. 2-day-old rats were exposed to anoxia in 100% nitrogen atmosphere. Rectal temperature was kept at 33 °C (typical for the rat neonates), or elevated to a level typical for febrile (39 °C) adults. Control rats were exposed to atmospheric air under the respective thermal conditions. The changes in MR and GR mRNA expression in hippocampus were examined 24 h after exposure. Our data show that hyperthermia with or without added anoxia, causes induction of MR mRNA expression in neonatal rat hippocampus without any effect on GR mRNA expression. We suggest this elevation of MR plays an important role in modulating the survival of neurons in the injured hippocampus.     

Selective modulation of glucocorticoid receptor function toward development of novel antiinflammation: lessons from a phenylpyrazolosteroid cortivazol

Abstract

A Frequent association of side effects has been a long-standing dilemma in clinical glucocorticoid therapy. Recent progress in molecular biology of glucocorticoid hormone action, however, has prompted researchers to tackle the dissociation of side effects and therapeutic effects based on the assumption that selective modulation of its receptor function could be achieved by as yet unknown compounds. Already a number of selective modulators of the glucocorticoid receptor (SGRMs) have been reported, and certain compounds have dissociating characteristics in vivo. We have addressed ligand-dependent modular recruitment of AF-1 function using a phenylpyrazologlucocorticoid cortivazol, suggesting the possibility of developing tissue-specific SGRMs. It should also be emphasized that SGRMs do not always have a steroid structure.