多发性硬化患者糖皮质激素受体和甲基强的松龙疗效的关系

Relationship between the Level of Glucocorticoid Receptor in Peripherial Blood Mononuclear Cells and the Effect of Methylprednisolone on Patients with Multiple Sclerosis

目的比较复发-缓解型多发性硬化(RRMS)、继发-进展型多发性硬化(SPMS)患者激素冲击治疗前、中、后外周血单核细胞(PBMC)中糖皮质激素受体(GR)蛋白含量和健康对照组的差异及其与甲基强的松龙(MP)疗效的关系。方法采用放射配体结合法测定45例健康成人、30例RRMS和6例SPMS患者PBMC中GR蛋白含量;使用扩展残疾状态量表(EDSS)评价MP疗效。结果(1)治疗前RRMS和SPMS患者的GR蛋白含量分别为(3765.83±1053.24)位点/细胞和(1599.67±448.79)位点/细胞,均低于健康对照组[(4249.09±616.10)位点/细胞](P<0.05);治疗中,RRMS和SPMS患者的GR蛋白含量分别为(3127.57±970.06)位点/细胞和(1219.67±346.27)位点/细胞,两者较治疗前均有下调(P<0.05);治疗后RRMS患者的GR蛋白含量上升至(4487.20±1473.18)位点/细胞,与健康对照组差异无统计学意义(P>0.05),而SPMS患者的GR蛋白含量上升至(3115.50±868.83)位点/细胞,但仍低于健康对照组(P<0.05)。(2)RRMS患者治疗后EDSS降至(2.70±1.80)分,与治疗前的(3.97±1.76)分相比差异有统计学意义(P<0.05);SPMS患者治疗后EDSS为(6.25±2.73)分与治疗前的(6.92±1.93)分之间差异无统计学意义(P>0.05)。(3)RRMS患者治疗前、后GR蛋白含量与同时期EDSS评分之间呈明显线性负相关(P<0.05)。结论GR蛋白含量的降低可能与MS的发生和发展有关,MP冲击治疗中症状一过性加重与GR蛋白含量下降相关,RRMS患者GR蛋白含量与MP的疗效相关。

Objective To investigate the difference of glucocorticoid receptors （GR） in peripheral blood mononuclear cells （PBMC） of patients with multiple sclerosis（MS） and health adults and the relationship between GR and the effect of intravenous injected methylprednisolone. Methods GR in PBMC were determined by radioligand binding assay in 30 patients with relapsing-remitting MS（RRMS）, 6 second-progressive MS（SPMS） and 45 controls. Results （1）When disease relapsed,GR in PBMC of MS were significantly lower [RRMS. （3765. 83± 1053. 24） site/cell; SPMS： （1599.67± 448. 79） site/cell] than those of controls [ （4249.09 ± 616.10） site/cell] ; during therapy, GR of RRMS[（3127.57±970. 06） site/cell] and SPMS[（1219.67±346.27） site/cell]were both decreased significantly; after therapy, GR of RRMS[（4487.20±1473. 18） site/cell] had no difference with controls, while SPMS[ （3115. 50± 868.83） site/cell] still significant lower than those of controls. （2） Compared to （3.97±1.76） score before therapy, extended disability status scale （EDSS） of RRMS decreased significantly to （2.70±1.80） score after therapy; while EDSS of SPMS had no difference between before therapy and after therapy. （3） There is linear correlation between GR （site/cell） and EDSS of RRMS both before therapy （r=-0. 441, P=0. 015） and after therapy（r=-0. 478, P=0. 008） . There is no linear correlation between GR （site/cell） and EDSS of SPMS. There is no linear correlation between GR（site/cell） and EDSS difference in different courses of therapy. Conclusions GR decrease has relationship with relapse of MS. There is correlation between significant decrease of GR during therapy and symptoms aggravation. The higher of GR expression in PBMC of RRMS patients,the lower EDSS of RRMS.