NS-398与前列腺素E_2对子宫内膜异位症子宫内膜细胞环氧合酶-2mRNA表达与凋亡的影响  

Effect of selective cyclooxygenase-2 inhibitor and prostaglandin E_2 on expres sion of COX-2 and apoptosis in human endometrial cells.

作　　者：李志刚[1] 郎景和[2] 冷金花[2] 刘东远[2] 刘珠凤[2] 孙大为[2] 朱兰[2] 

机构地区：[1]广东省人民医院妇产科,广州510080 [2]中国医学科学院北京协和医科大学北京协和医院妇产科

出　　处：《现代妇产科进展》2005年第1期30-33,共4页Progress in Obstetrics and Gynecology

摘　　要：目的 :探讨选择性环氧合酶 2 (COX- 2 )抑制剂NS -398与前列腺素E(PGE2 )对子宫内膜异位症患者子宫内膜细胞COX -2mRNA表达与细胞凋亡的影响。方法 :以体外培养的子宫内膜细胞为研究对象 ,分别用NS- 398与PGE2 处理。采用RT- PCR法、MTT法、酶联免疫吸附试验 (ELISA)和流式细胞术 ,检测刺激前后COX -2mRNA表达量、细胞增殖、凋亡与细胞周期分布情况以及上清液中凋亡抑制蛋白Bcl 2与PGE2 的释放量。结果 :NS- 398以剂量与时间依赖方式抑制COX -2mRNA的表达以及PGE2 与Bcl -2的分泌 ,抑制子宫内膜细胞增殖 ,诱导细胞凋亡 ,改变细胞周期分布 ,增加G0 /G1期细胞的比例。PGE2以时间与剂量依赖方式刺激子宫内膜细胞的COX- 2mRNA的表达 ,使Bcl- 2释放增加。同时 ,PGE2 可以逆转NS- 398对子宫内膜细胞的抑制作用 ,细胞增殖重新活跃 ,改变细胞周期分布 ,减少G0 /G1期细胞的比例 ,抑制细胞凋亡。结论 :COX- 2选择性抑制剂NS- 398,促进细胞凋亡 ,抑制细胞增殖 ,其机制可能与抑制COX -2的表达 ,降低PGE2 以及Bcl- 2释放 ,和改变细胞周期有关。PGE2 在体外能够刺激子宫内膜细胞COX- 2的表达升高 ,促进细胞增殖 ,抑制细胞凋亡。Objective:To determine the effects of selective cycl ooxygenase-2 (COX-2) inhibitor NS-398 and PGE 2 on the expression of COX-2, the releasing of PGE 2 and Bcl-2, and the apoptosis in primary cultured endometria l cells.Methods:The cultured endometrial cells(ESCs) were div ided into two groups, which were treated with selective COX-2 inhibitor NS-398, and PGE 2 respectively. Total RNA was extracted for RT-PCR used to determine the COX-2 mRNA expression. ELISA w as used to detect the PGE 2 and Bcl-2 releases in the culture supernatant. MTT a ss ay was used to determine the proliferation of these cells, and flow cytometry to observe the apoptosis and distribution of cell cycle between with and without t reatment.Results:NS-398 could inhibit the expression of COX - 2mRNA and then reduced the PGE 2 and Bcl-2 release in a time- and dose-depen dent mode, and then inhibited the cell proliferation and induced apoptosis through in creasing the ratio of the G 0/G 1 cells. PGE 2 could stimulate the endometria l cells to express COX-2 mRNA an d then reduced the Bcl-2 release in a time- and dose-dependent mode, and then pr omoted the cell proliferation of cell and inhibited apoptosis through changing t he ratio of the G 0/G 1 cells.Conclusions:NS-398 inhibit s the proliferation of end ometrial cells through decreasing PGE 2 and Bcl-2, and affecting the distribut ion of cell cycle and inducing apoptosis, which indicating that selective COX-2 in h ibitor may be a new way of the treatment of endometriosis. PGE 2 promotes the p roliferation of the cells by inhibiting apoptosis.

关 键 词：子宫内膜异位症 环氧合酶 前列腺素E类 细胞凋亡 

分 类 号：R711.71[医药卫生—妇产科学]