过氧化物酶体增殖物激活受体γ激动剂对生长激素分泌型垂体腺瘤的影响

Effects of peroxisome proliferator activated receptor γ agonist on growth hormone secreting pituitary adenoma

目的：研究过氧化物酶体增殖物激活受体γ（PPARγ）激动剂对生长激素分泌型垂体腺瘤细胞生长及激素分泌的影响。方法：（1）细胞实验：罗格列酮作用于GH3细胞株，分析瘤细胞增殖和凋亡．电镜观察形态。（2）动物实验：罗格列酮作用于小鼠模型，监测肿瘤大小及生长激素水平。结果：罗格列酮将瘤细胞阻滞在GO—G1期并出现细胞凋亡（P〈0．05）；电镜证实瘤细胞发生凋亡。动物实验显示治疗组和对照组的肿瘤体积分别为（768．97±103．04）mm3和（1248．15±254．51）mm3（P〈0．05），生长激素水平分别为（154．57±32．61）ng／mL和（598．37±40．03）nlg／mL（P〈0．05）。结论：PPARγ激动剂罗格列酮能抑制GH3细胞增殖．诱导其凋亡，降低激素分泌水平。罗格列酮有可能成为治疗生长激素分泌型垂体腺瘤的具有广泛前景的药物。

Objective To evaluate the influences of peroxisome proliferator activated receptor γ （PPARγ） activator on cell proliferation and growth hormone （GH） secretion of pituitary adenoma in vitro and in rats. Methods （ 1 ） Cell experiment ： rosiglitazone was administered on GH3 cell lines. The proliferation and apoptosis of GH3 cells was validated by MTT staining and transmission electron microscope. （2） Animal experiment： 120 mg/ （kg.d） of rosiglitazone was given to BALB/c nude mice model for 6 weeks. Tumor size was recorded every 3 days while GH level was detected every 2 weeks. Results GH3 ceils treated with rosiglitazone could induce G0/G1 cell- cycle arrest （P 〈 0.01） and apoptosis which was validated by transmission electron microscope. Tumor size of rosiglitazone group and control group were （768.97 ± 103.04） mm3 vs. （1 248.15 ± 254.51） mm3 （P 〈 0.05）; and serum GH level were （154.57 ± 32.61） ng/mL vs. （598.37±40.03） ng/mL （P 〈 0.05）. Conclusions PPARγ agonist rosiglitazone could inhibit the proliferation of GH3 cells, induce the apoptosis, and decrease serum GH level. Rosiglitazone may become a drug having a wide range of promising for treating GH-secreting pituitary adenoma.