目的 研究溴隐亭对大鼠催乳素（prolactinoma，PRL）瘤表达bcl-2、Bax的影响。方法 （1）用皮下植入17β-雌二醇的方法制备大鼠催乳素瘤模型，同时设立10只大鼠为对照组；（2）将成功诱发出催乳素瘤的大鼠随机分2组，分别给予自来水（安慰剂组）、溴隐亭（溴隐亭组）灌胃，对照组也给予安慰剂灌胃，用药4周后处死动物，垂体称重，测定PRL、Bax、bcl-2的表达水平。结果 （1）17β-雌二醇组大鼠血清PRL水平［（4236.9±416.9） vs （121.2±12.8） ng/ml］和垂体重量［（62.0±5.1） vs （13.8±1.2） mg］均明显高于对照组（P＜0.01），证实17β-雌二醇组成功诱发出大鼠泌乳素瘤。（2）溴隐亭组血清PRL水平和垂体重量低于安慰剂组（P＜0.01），bcl-2表达水平较安慰剂组明显下降［（1.8±0.5） vs (4.0±0.6)，P＜0.01］，Bax表达水平明显增高［（4.5±0.6） vs ( 1.0±0.3),P＜0.01］。结论 抑制bcl-2的表达，刺激Bax的表达，从而促进催乳素瘤细胞的凋亡可能是溴隐亭抗催乳素瘤的重要机制之一。
Abstract
Objective To study the effect of bromocriptine on expression of Bax and bcl-2 in rat prolactinoma. Methods Firstly, to develop prolactinoma rats model. Adult Wistar rats were divided into two groups at random. The rats in control group were subscutaneously implanted with a blank implant . Rats in 17β-estradiol group were implanted with 17β-estradiol -containing implants. Secondly, Rats in 17β-estradiol group were divided into two groups at random, i.e. placebo group and bromocriptine group. Water was given to rats in placebo group. Bromocriptine was orally adminstered to rats in bromocriptine group. After 4 weeks of treatment, all the animals were sacrificed. Each pituitary gland was weighed. Serum prolactin(PRL) levels were measured by RIA. Expression level of Bax and bcl-2 in pituitary tissue were measured by Western blotting. Results (1)The weights of pituitary gland and PRL levels in 17β-estradiol group were significantly higher than those in control group (P <0.01,repectively). (2)The expression level of bcl-2 in bromocriptine group was significantly lower than that in placebo group (P<0.01). (3)The expression level of Bax in bromocriptine group was significantly higher than that in placebo group (P<0.01). Conclusion Bromocriptine has potential preventive effect against estrogen-induced prolactinoma in rats. The decrease of bcl-2 expression level and increase of Bax expression level may be involved in the mechanism of anti-prolactinoma effect of bromocriptine.
关键词
催乳素瘤 /
大鼠 /
凋亡 /
Bax /
bcl-2
Key words
prolactinoma /
rats /
apoptosis /
Bax /
bcl-2
{{custom_sec.title}}
{{custom_sec.title}}
{{custom_sec.content}}
参考文献
［1］ Yonezawa K, Tamaki N, Kokunai T. Effects of bromocriptine and terguride on cell proliferation and apoptosis in the estrogen-stimulated anterior pituitary gland of the rat［J］. Neurol Med Chir (Tokyo), 1997,37(12):901-906.
［2］ 梁立武，徐 春.垂体肿瘤转化基因(PTTG)在人垂体腺瘤中的表达［J］. 武警医学,2005，16(10):595-597.
［3］ 刘亚力，邱文娟，杨雪梅，等.多巴胺激动药对大鼠垂体组织表达Pit-1作用的研究［J］，武警医学，2008，19（1）：11-13.
［4］ Gruszka A, Pawlikowski M, Kunert-Radek J. Anti-tumoral action of octreotide and bromocriptine on the experimental rat prolactinoma: anti-proliferative and pro-apoptotic effects［J］. Neuro Endocrinol Lett, 2001,22(5):343-348.
［5］ Wasko R, Wolun-Cholewa M, Bolko P,et al. Effect of bromocriptine on cell apoptosis and proliferation in GH3 cell culture［J］.Neuro Endocrinol Lett,2004,25(3):223-228.
［6］ Rowther F B, Richardson A, Clayton R N, et al. Bromocriptine and dopamine mediate independent and synergistic apoptotic pathways in pituitary cells［J］. Neuroendocrinology,2010,91(3):256-267.
［7］ Gruszka A, Kunert-Radek J, Pawlikowski M. The effect of octreotide and bromocriptine on expression of a pro-apoptotic Bax protein in rat prolactinoma［J］. Folia Histochem Cytobiol,2004,42(1):35-39.
［8］ Rowther F B, Richardson A, Clayton R N，et al. Bromocriptine and dopamine mediate independent and synergistic apoptotic pathways in pituitary cells［J］. Neuroendocrinology,2010,91(3):256-267.
PDF(560 KB)
