人脐带间充质干细胞移植治疗Graves病小鼠的疗效

Efficacy of umbilical-cord mesenchymal stem cells transplantation in treatment of mice with Graves disease

目的探讨人脐带间充质干细胞(UC-MSC)对Graves病(GD)模型小鼠的治疗作用。方法将48只18周龄雌性GD小鼠随机分为G0、G1、G2、G3组各12只,G1组和G3组给予丙硫氧嘧啶(PTU)50 mg×60 d灌胃,同时G2组和G3组于经尾静脉移植人MSC 1次,G0组不治疗。定期称取小鼠体质量,常规测定血象与谷丙转氨酶(GPT),化学发光法测定血清游离甲状腺素(FT4),酶联吸附法(ELISA)法测定血清甲状腺刺激抗体(TSAb),HE染色观察甲状腺病理改变。结果 26周龄时体质量G2组(28.6±2.8)g、G3组(29.4±3.1)g,高于G0组的(25.3±2.8)g、G1组的(25.6±3.4)g,P均<0.05。26周龄时,白细胞G2组(6.7±1.4)×109/L、G3组(7.3±1.2)×109/L,高于G0组的(4.2±0.6)×109/L、G1组的(4.3±1.1)×109/L,P均<0.05;GPT G2组(34.8±12.5)U/L、G3组(36.7±14.7)U/L,低于G0组的(57.2±13.5)U/L、G1组的(59.0±11.6)U/L,P均<0.05。26周龄时,血清FT4及TSAb水平G2组分别为(6.2±1.2)pmol/L、(4.7±0.8)U/mL,G3组分别为(5.9±1.3)pmol/L、(3.4±0.7)U/mL,低于G0组的(10.0±1.8)pmol/L、(8.4±1.0)U/mL,P均<0.05。甲状腺滤泡上皮增生与新生滤泡G2组和G3组较G0组明显减少。结论 UC-MSC对Graves病模型鼠有显著疗效,安全且无排斥反应。

Objective To investigate the efficacy of umbilical-cord mesenchymal stem cells （UC-MSC） transplantation in the treatment of mice with Graves disease （GD）. Methods Forty-eight 18-week-old GD female mice were divided into 4 groups ： group 1 （ G1 ） was treated with propyhhiouracil （ PTU ） （ 50 mg× 60 d）, group 2 （G2） was transplanted with 1 × 106 UC-MSC once through caudal vein, group 3 （G3） was treated with PTU（50 mg x60 d） and UC-MSC, and group 0 （GO） was treated with 0.5 mL normal saline as controls. Blood analysis, glutamic pyruvic transaminase （GPT） and body weight were assessed every two weeks. Chemiluminescence was used to detect the levels of serum free thyroxine （T4）. Enzyme linked immunosorbent assay （ELISA） was used to measure the levels of serum thyroid stimulating antibody （TSAb）. The pathological changes of the thyroids were observed by HE staining. Results At week 26, the body weight of mice inG2 [（28.6 ± 2.8） g] andG3 [（29.4 ± 3.1） g ] was separately higher than that of GO [ （25.3 ± 2.8） g ] andG1 [ （25.6 ± 3.4） g ] （P〈0.05）. At week 26, the leukoeytesin G2 [（6.7 ± 1.4） ×109/L ] and G3 [ （7.3 ±1.2） × 109/L] were both increased compared with those in GO [ （4.2 ±0.6） × 109/L] and G1 [ （4.3 ±1.1）× 109/L] （P 〈0.05）, but the GPT in G2 （34.8 ± 12.5） U/L and G3 （36.7 ± 14.7） U/L were decreased compared with those in GO （57.2 ± 13.5） U/L and G1 （59.0 ± 11. 6） U/L （ P 〈 0.05 ）. At week 26, the serum FT4 and TSAb levels in G2 [ （6.2 ± 1.2） pmol/L, （4.7 ± 0.8 ） U/mL ] and G3 [ （5.9 ± 1.3 ） pmol/L, （ 3.4 ± 0.7 ） U/mL ] were both lower than those in GO [ （ 10.0 ± 1.8） pmol/L, （8.4 ± 1.0） U/mL] （P 〈0.05）. The thyroid follicular epithelial hyperplasia and new follicular were significantly decreased in G2 and G3 compared with those of GO. Conclusion UC-MSC is very effective in treating GD mice, and it is safe and free of rejection reactions.