【作者】 黄莹；

【导师】 卢家红； 赵重波； 朱雯华；

【作者基本信息】 复旦大学 ， 神经病学， 2010， 硕士

【摘要】 目的：探讨重症肌无力(MG)患者外周血淋巴细胞中糖皮质激素受体(GR)α和βmRNA表达与MG患者对糖皮质激素(GC)疗效的相关性。材料与方法：第一部分采用实时定量逆转录.聚合酶链反应(real-time quantitative RT-PCR)方法对43例MG患者和14例正常对照者外周血白细胞中的GRa和βmRNA表达水平进行检测,所有MG病人均接受了目标剂量(1mg/kg)范围内的GC治疗,其中全身型MG28例,18例对治疗敏感、10例抵抗；眼肌型15例,10例对治疗敏感,5例抵抗。第二部分采用实时定量RT-PCR的方法对5例GC抵抗的眼肌型MG患者在大剂量激素冲击治疗前后的外周血GRα、βmRNA的表达水平进行检测。结果：在GC治疗敏感的全身型和眼肌型MG患者中,其GRαmRNA表达水平明显高于GC抵抗者；与正常健康对照的GRβmRNA表达水平相比,GC治疗敏感和抵抗的全身型和眼肌型MG患者均无明显差别。在大剂量激素冲击治疗后的眼肌型MG患者中,临床症状明显改善,其外周血白细胞中的GRαmRNA表达水平较激素冲击治疗前明显升高,而GRβmRNA的表达水平却有降低。结论：对于目标剂量范围内的GC治疗,全身型和眼肌型MG患者的抵抗可能与GRαmRNA的表达水平下降有关,而与GRβmRNA的表达水平则无明显相关性。大剂量激素冲击治疗可以显著改善GC目标治疗剂量抵抗的眼肌型MG症状,可能与通过上调GRαmRNA表达水平并下调GRβmRNA表达水平从而提高患者对GC的敏感性有关。更多还原

【Abstract】 Objective:To explore the relationship between glucocorticoid efficacy and expression of glucocorticoid receptor(GR) aandβmRNA in peripheral blood white cell of patients with general and ocular myasthenia gravis(MG). Methods:First part: Real-time quantitative reverse transcription-polymerase chain reaction(real-time quantitative RT-PCR) was used to quantite the expression of GRaandβmRNA in peripheral blood white cells of 43 MG patients, all of which had been given GC treatment (target dosasge less than 1mg/kg.d).18 cases of general MG patients were sensitive to GC, and 10 cases of general MG patients were resistant to GC.10 cases of ocular MG patients were sensitive to GC and 5 cases of ocular MG patients were resistant to GC. Second part:We also used real-time quantitative RT-PCR to quantite the expression of GRαandβmRNA in peripheral blood white cells of 5 cases with ocular MG patients resistant to GC before and after accepting large dosage infusion of GC. Result:The expression of GRαmRNA in general and ocular MG patients sensitive to GC were higher than those in normal controls, also significantly higher than those in MG patients resistant to GC. There was no significant difference in the expression of GRβmRNA among general and ocular MG patients and the normal control. However, a significant higher expression of GRαand a lower expression of GRPmRNA was noticed in ocular MG patients after large dosage of GC treatment. Conclusion:The higher expression of GRαmRNA in general and ocular MG patients may be related to thier sensitivity to GC therapy. However, the relation between GRβmRNA expression and GC resistency is not clarified in our MG patients. In addition, high dosage of GC infusion can improve the syptoms and signs of GCresistant ocular MG patients. The possible mechanism is due to increasing sensitivity to GC induced by up-regulated GRαmRNA expression and down-regulated GRβmRNA expression.更多还原