CAJ | 학술논문

观察整体条件下褪黑素(melatonin,MLT)抑制由17-β-雌二醇(E2)诱发的垂体催乳素(prolactin,PRL)瘤的生长，并初步探讨其作用机制。方法以雄性Sprague-Dawley大鼠皮下埋植E2药泵，诱发PRL瘤。实验组大鼠分5组，在诱瘤之前每日定时分别皮下注射0.05、0.25、0.50、1.00和2.00mg MLT，共90d；对照组大鼠皮下注射等体积4％乙醇-生理盐水。结果 (1)给予0.05、0.25、0.50、1.00和2.00mgMLT处理组PRL瘤重量分别较对照组降低25.91％(P＞0.05)、48.78％(P＜0.01)、36.78％(P＜0.05)、31.04％(P＞0.05)和35.22％(P＞0.05)；(2)Northern Blot分析表明，注射0.05、0.25、0.50mg MLT组PRL瘤细胞PRL mRNA表达水平分别比对照组降低33.67％(P＜0.05)、25.51％(P＜0.05)和41.84％(P＜0.01)；原代培养的PRL瘤细胞原位杂交实验也获得类似结果；(3)激光扫描共聚焦显微镜检测结果显示，0.05、0.25和0.50mg MLT组PRL瘤细胞DNA的相对含量分别较对照组降低40.73％(P＜0.001)、51.15％(P＜0.001)和60.23％(P＜0.001)；(4)紫外分光光度法测定显示，0.05、0.25、0.50、1.00和2.00mg MLT组血浆过氧化脂质水平分别比对照组降低26.45％(P＜0.05)、23.97％(P＜0.05)、47.11％(P＜0.001)、66.12％(P＜0.001)和64.46％(P＜0.001)。其量-效关系的相关系数为-0.8257(P＜0.05)。结论一定剂量的MLT对E2诱发的PRL瘤生长具有显著的抑制作用。MLT的这种抑瘤作用可能是通过其抑制PRL基因高表达和DNA合成实现的。
관찰정체조건하퇴흑소(melatonin,MLT)억제유17-β-자이순(E2)유발적수체최유소(prolactin,PRL)류적생장，병초보탐토기작용궤제。방법이웅성Sprague-Dawley대서피하매식E2약빙，유발PRL류。실험조대서분5조，재유류지전매일정시분별피하주사0.05、0.25、0.50、1.00화2.00mg MLT，공90d；대조조대서피하주사등체적4％을순-생리염수。결과 (1)급여0.05、0.25、0.50、1.00화2.00mgMLT처리조PRL류중량분별교대조조강저25.91％(P＞0.05)、48.78％(P＜0.01)、36.78％(P＜0.05)、31.04％(P＞0.05)화35.22％(P＞0.05)；(2)Northern Blot분석표명，주사0.05、0.25、0.50mg MLT조PRL류세포PRL mRNA표체수평분별비대조조강저33.67％(P＜0.05)、25.51％(P＜0.05)화41.84％(P＜0.01)；원대배양적PRL류세포원위잡교실험야획득유사결과；(3)격광소묘공취초현미경검측결과현시，0.05、0.25화0.50mg MLT조PRL류세포DNA적상대함량분별교대조조강저40.73％(P＜0.001)、51.15％(P＜0.001)화60.23％(P＜0.001)；(4)자외분광광도법측정현시，0.05、0.25、0.50、1.00화2.00mg MLT조혈장과양화지질수평분별비대조조강저26.45％(P＜0.05)、23.97％(P＜0.05)、47.11％(P＜0.001)、66.12％(P＜0.001)화64.46％(P＜0.001)。기량-효관계적상관계수위-0.8257(P＜0.05)。결론일정제량적MLT대E2유발적PRL류생장구유현저적억제작용。MLT적저충억류작용가능시통과기억제PRL기인고표체화DNA합성실현적。
Objective To examine the inhibitory effect of melatonin (MLT) on the development of pituitary prolactin-producing tumors (prolactinoma) induced by 17-β-estradiol (E2), in vivo, and explore MLT′s oncostatic mechanisms. Methods The prolactinomas were established by implanting E2-1aden silastic capsules subcutaneously in Sprague-Dawley male rats. MLT doses 0.05, 0.25, 0.50, 1.00, and 2.00 mg/rat were administrated separately to 5 groups subcutaneously starting seven days prior to tumor induction for 97 days. The matched controls were given equal volumes of 4% alcohol in saline. Results (1) The prolactinoma weights in 0.05, 0.25, 0.50, 1.00 and 2.00 mg MLT dose groups were 25.91% (P＞0.05), 48.78% (P ＜0. 01), 36.78% (P ＜0.05), 31.04% (P＞ 0.05) and35.22% (P＞ 0.05)respectively which were lower than that of control group;(2) The PRL mRNA levels of prolactinoma in 0.05,0.25,and 0.50mg MLT dose groups were 33.67% (P＜0.05), 25.51% (P＜0.05) and 41.84%(P＜0.01)respectively which were lower than that of control group as estimated by Northern Blot, and the in situ hybridization studies; (3) The DNA contents of prolactinoma in 0. 05, 0. 25 and 0. 50 mg MLT dose groups were 40. 73% (P＜0.001), 51.15% (P＜0.001) and 60. 23% (P ＜0. 001) respectively which were lower than that of control group by laser scanning confocal microscopy; (4) Plasma peroxidative lipid contents in 0.05,0.25,0.50,1.00 and 2.00 mg MLT dose groups were 26.45% (P ＜0.05), 23.97% (P ＜0.05), 47. 11%(P ＜0.001), 66. 12%(P ＜0.001)and64.46% (P ＜0.001)respectively which were lower than that of control group. The correlation coefficient between MLT doses and plasma peroxidative lipid contents was - 0.8257 (P＜0.05). Conclusions MLT in suitable doses is able to inhibit the development of E2-induced prolactinoma by inhibiting the expression of PRL gene and the DNA synthesis. The link between MLT antioxidative action and its inhibitory effect on development of prolactinoma should be further investigated.