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目的检测多发性硬化(MS)患者外周血单个核细胞(PBMC)中糖皮质激素受体(GR)蛋白与 mRNA 亚型:GRα mRNA、GRβ mRNA 的表达,探讨 GR 蛋白和 GRα mRNA、GRβ mRNA 的表达与甲泼尼龙静脉冲击治疗(IVMP)疗效间的关系。方法采用放射配体结合法测定20例缓解复发型MS(RRMS)、6例继发进展型 MS(SPMS)及26名健康对照 GR 蛋白数量;采用半定量逆转录聚合酶链反应法测定 GRα mRNA、GRβ mRNA 的表达,使用扩展残疾状态量表(EDSS)评价 IVMP 疗效。结果(1)IVMP 前 RRMS 和 SPMS 患者 GR 蛋白数量分别为(3.8±0.2)×10~3位点/细胞和(1.6±0.2)×10~3位点/细胞,均显著低于健康对照组[(4.2±0.8)×10~3位点/细胞,P<0.05]。RRMS 患者 IVMP前 GR 蛋白数量与 EDSS 呈线性负相关(r=-0.441,P=0.015)。(2)以磷酸甘油醛脱氢酶的表达作为内参照,RRMS 患者 GRα mRNA 的表达水平(0.792±0.177)与健康对照组(0.805±0.158)差异无统计学意义,而 SPMS 患者的表达水平(0.315±0.129)明显低于健康对照(P<0.05)。(3)RRMS 和SPMS 患者 PBMC 中均有 GRβ mRNA 的表达,健康对照组未检出 GRβ mRNA 表达。(4)RRMS、SPMS患者 GRβ mRNA 的表达分别占各自 GRα mRNA 的43.98%±2.40%和140.01%±78.75%。结论RRMS 患者 GRβ mRNA 的低水平表达不影响 IVMP 疗效。SPMS 患者 GRα mRNA 表达水平显著降低和(或)GRβ mRNA 表达水平显著升高导致 GC 抵抗。
Objective To detect the expression of GRα mRNA and GRβ mRNA in peripheral blood mononuclear cells (PBMC) of patients with multiple sclerosis (MS) and to investigate the relationship between GR protein, GRα mRNA and GRβ mRNA Expressions and the Effect of Methylprednisolone Intravenous Impact Therapy (IVMP). Methods Radioligand binding assay was used to determine the number of GR proteins in 20 patients with relapsed-onset MS (RRMS), 6 patients with progressive-phase MS (SPMS) and 26 healthy controls. The GRα mRNA was measured by semi-quantitative reverse transcription polymerase chain reaction , GRβ mRNA expression, the use of Extended Disability Status Scale (EDSS) evaluation of IVMP efficacy. Results (1) The numbers of GR protein in RRMS and SPMS patients before IVMP were (3.8 ± 0.2) × 10 ~ 3 sites and (1.6 ± 0.2) × 10 ~ 3 sites / cells respectively, which were significantly lower than those in healthy controls [(4.2 ± 0.8) × 10 ~ 3 sites / cell, P <0.05]. There was a linear negative correlation between the amount of pre-IV GR protein and EDSS in patients with RRMS (r = -0.441, P = 0.015). (2) The expression of GRα mRNA in RRMS patients (0.792 ± 0.177) was not significantly different from that in healthy controls (0.805 ± 0.158), with the expression of glyceraldehyde-6-phosphate dehydrogenase as internal reference. 0.315 ± 0.129) was significantly lower than the healthy controls (P <0.05). (3) The expressions of GRβ mRNA both in PBMC of patients with RRMS and SPMS were not detected in healthy control group. (4) The expression of GRβ mRNA in RRMS and SPMS patients accounted for 43.98% ± 2.40% and 140.01% ± 78.75% of the respective GRα mRNA. Conclusion The low level expression of GRβ mRNA in RRMS patients does not affect the efficacy of IVMP. Significantly decreased GRα mRNA expression and / or GRβ mRNA expression in SPMS patients led to GC resistance.