目的 研究促性腺激素释放激素( GnRH)类似物抑制卵巢癌裸鼠皮下移植瘤生长,同时保护化疗裸鼠卵巢功能的双重作用.方法 构建卵巢癌ES-2细胞裸鼠皮下移植瘤模型,随机分为6组(每组6只):(1)生理盐水(NS)组:皮下注射NS 0.1ml/d,1周后腹腔注射NS 0.2ml/周；(2)顺铂(DDP)组:皮下注射NS 0.1ml/d,1周后每周腹腔注射5 mg/kg DDP；(3)戈舍瑞林(goserelin)组:皮下注射goserelin 100 μg/d,1周后腹腔注射NS0.2 ml/周；(4) goserelin+ DDP组:皮下注射goserelin 100 μg/d,1周后每周腹腔注射5 mg/kg DDP；(5)西曲瑞克(cetrorelix)组:皮下注射cetrorelix 100 μg/d,1周后腹腔注射NS0.2 ml/周；(6) cetrorelix+ DDP组:皮下注射cetrorelix 100 μg/d,1周后每周腹腔注射5 mg/kg DDP.用药21 d,观察29 d.比较各组裸鼠体质量、移植瘤体积、移植瘤组织中细胞增殖相关核抗原Ki-67的阳性率、动情周期、卵巢各级卵泡比例、血清抗苗勒管激素(AMH)、卵泡刺激素(FSH)、雌二醇、孕酮水平的差异.结果 各组裸鼠体质量无明显差异(P＞0.05),用药第29天NS组为(19.8 ±2.2)g,DDP组(20.5±1.4)g,gosereline组(19.6±0.9)g,goserelin+DDP组(19.7±1.6)g,cetrorelix组(20.7±2.2)g,cetrorelix+ DDP组(19.0±1.7)g,分别比较,差异均无统计学意义(P＞0.05).用药第12天裸鼠移植瘤体积:NS组为(241±179) mm3,DDP组(78±20) mm3,gosereline组(78±55) mm3,goserelin+ DDP组(64±48) mm3,cetrorelix组(78±64) mm3,cetrorelix+ DDP组(70±19) mm3,用药组均明显小于NS组,差异有统计学意义(P＜0.05)；第15、19、22、26、29天各用药组移植瘤体积也均明显小于NS组(P＜0.05).NS组Ki-67阳性率为(33± 10)％,DDP组为3.5％,goserelin组8.8％,goserelin+ DDP组1.5％,cetrorelix组(23±11)％,cetrorelix+ DDP组(8±6)％,DDP组、goserelin组和goserelin +DDP组均明显低于NS组,差异有统计学意义(P＜0.05).goserelin组原始卵泡+窦前卵泡率为(71.5±8.1)％,goserelin+DDP组为(62.4± 4.1)％,cetrorelix组(71.2±7.4)％,cetrorelix+DDP组(63.8±2.9)％,均明显高于DDP组的(47.0±4.8)％,差异均有统计学意义(P＜0.05).goserelin组血清AMH水平为(98±27) ng/ml,明显高于NS组的(66±17) ng/ml,差异有统计学意义(P＜0.05)；各组裸鼠血清FSH、雌二醇和孕酮水平分别比较,差异均无统计学意义(P＞0.05).结论 GnRH类似物能抑制卵巢癌裸鼠皮下移植瘤的生长,同时上调AMH分泌、减少动情次数、延长动情周期时间、增加原始卵泡+窦前卵泡率,从而保护卵巢功能.
目的 研究促性腺激素釋放激素( GnRH)類似物抑製卵巢癌裸鼠皮下移植瘤生長,同時保護化療裸鼠卵巢功能的雙重作用.方法 構建卵巢癌ES-2細胞裸鼠皮下移植瘤模型,隨機分為6組(每組6隻):(1)生理鹽水(NS)組:皮下註射NS 0.1ml/d,1週後腹腔註射NS 0.2ml/週；(2)順鉑(DDP)組:皮下註射NS 0.1ml/d,1週後每週腹腔註射5 mg/kg DDP；(3)戈捨瑞林(goserelin)組:皮下註射goserelin 100 μg/d,1週後腹腔註射NS0.2 ml/週；(4) goserelin+ DDP組:皮下註射goserelin 100 μg/d,1週後每週腹腔註射5 mg/kg DDP；(5)西麯瑞剋(cetrorelix)組:皮下註射cetrorelix 100 μg/d,1週後腹腔註射NS0.2 ml/週；(6) cetrorelix+ DDP組:皮下註射cetrorelix 100 μg/d,1週後每週腹腔註射5 mg/kg DDP.用藥21 d,觀察29 d.比較各組裸鼠體質量、移植瘤體積、移植瘤組織中細胞增殖相關覈抗原Ki-67的暘性率、動情週期、卵巢各級卵泡比例、血清抗苗勒管激素(AMH)、卵泡刺激素(FSH)、雌二醇、孕酮水平的差異.結果 各組裸鼠體質量無明顯差異(P＞0.05),用藥第29天NS組為(19.8 ±2.2)g,DDP組(20.5±1.4)g,gosereline組(19.6±0.9)g,goserelin+DDP組(19.7±1.6)g,cetrorelix組(20.7±2.2)g,cetrorelix+ DDP組(19.0±1.7)g,分彆比較,差異均無統計學意義(P＞0.05).用藥第12天裸鼠移植瘤體積:NS組為(241±179) mm3,DDP組(78±20) mm3,gosereline組(78±55) mm3,goserelin+ DDP組(64±48) mm3,cetrorelix組(78±64) mm3,cetrorelix+ DDP組(70±19) mm3,用藥組均明顯小于NS組,差異有統計學意義(P＜0.05)；第15、19、22、26、29天各用藥組移植瘤體積也均明顯小于NS組(P＜0.05).NS組Ki-67暘性率為(33± 10)％,DDP組為3.5％,goserelin組8.8％,goserelin+ DDP組1.5％,cetrorelix組(23±11)％,cetrorelix+ DDP組(8±6)％,DDP組、goserelin組和goserelin +DDP組均明顯低于NS組,差異有統計學意義(P＜0.05).goserelin組原始卵泡+竇前卵泡率為(71.5±8.1)％,goserelin+DDP組為(62.4± 4.1)％,cetrorelix組(71.2±7.4)％,cetrorelix+DDP組(63.8±2.9)％,均明顯高于DDP組的(47.0±4.8)％,差異均有統計學意義(P＜0.05).goserelin組血清AMH水平為(98±27) ng/ml,明顯高于NS組的(66±17) ng/ml,差異有統計學意義(P＜0.05)；各組裸鼠血清FSH、雌二醇和孕酮水平分彆比較,差異均無統計學意義(P＞0.05).結論 GnRH類似物能抑製卵巢癌裸鼠皮下移植瘤的生長,同時上調AMH分泌、減少動情次數、延長動情週期時間、增加原始卵泡+竇前卵泡率,從而保護卵巢功能.
목적 연구촉성선격소석방격소( GnRH)유사물억제란소암라서피하이식류생장,동시보호화료라서란소공능적쌍중작용.방법 구건란소암ES-2세포라서피하이식류모형,수궤분위6조(매조6지):(1)생리염수(NS)조:피하주사NS 0.1ml/d,1주후복강주사NS 0.2ml/주；(2)순박(DDP)조:피하주사NS 0.1ml/d,1주후매주복강주사5 mg/kg DDP；(3)과사서림(goserelin)조:피하주사goserelin 100 μg/d,1주후복강주사NS0.2 ml/주；(4) goserelin+ DDP조:피하주사goserelin 100 μg/d,1주후매주복강주사5 mg/kg DDP；(5)서곡서극(cetrorelix)조:피하주사cetrorelix 100 μg/d,1주후복강주사NS0.2 ml/주；(6) cetrorelix+ DDP조:피하주사cetrorelix 100 μg/d,1주후매주복강주사5 mg/kg DDP.용약21 d,관찰29 d.비교각조라서체질량、이식류체적、이식류조직중세포증식상관핵항원Ki-67적양성솔、동정주기、란소각급란포비례、혈청항묘륵관격소(AMH)、란포자격소(FSH)、자이순、잉동수평적차이.결과 각조라서체질량무명현차이(P＞0.05),용약제29천NS조위(19.8 ±2.2)g,DDP조(20.5±1.4)g,gosereline조(19.6±0.9)g,goserelin+DDP조(19.7±1.6)g,cetrorelix조(20.7±2.2)g,cetrorelix+ DDP조(19.0±1.7)g,분별비교,차이균무통계학의의(P＞0.05).용약제12천라서이식류체적:NS조위(241±179) mm3,DDP조(78±20) mm3,gosereline조(78±55) mm3,goserelin+ DDP조(64±48) mm3,cetrorelix조(78±64) mm3,cetrorelix+ DDP조(70±19) mm3,용약조균명현소우NS조,차이유통계학의의(P＜0.05)；제15、19、22、26、29천각용약조이식류체적야균명현소우NS조(P＜0.05).NS조Ki-67양성솔위(33± 10)％,DDP조위3.5％,goserelin조8.8％,goserelin+ DDP조1.5％,cetrorelix조(23±11)％,cetrorelix+ DDP조(8±6)％,DDP조、goserelin조화goserelin +DDP조균명현저우NS조,차이유통계학의의(P＜0.05).goserelin조원시란포+두전란포솔위(71.5±8.1)％,goserelin+DDP조위(62.4± 4.1)％,cetrorelix조(71.2±7.4)％,cetrorelix+DDP조(63.8±2.9)％,균명현고우DDP조적(47.0±4.8)％,차이균유통계학의의(P＜0.05).goserelin조혈청AMH수평위(98±27) ng/ml,명현고우NS조적(66±17) ng/ml,차이유통계학의의(P＜0.05)；각조라서혈청FSH、자이순화잉동수평분별비교,차이균무통계학의의(P＞0.05).결론 GnRH유사물능억제란소암라서피하이식류적생장,동시상조AMH분비、감소동정차수、연장동정주기시간、증가원시란포+두전란포솔,종이보호란소공능.
Objective To investigate the influence of gonadotropin-releasing hormone (GnRH) analogues on ovarian cancer and ovarian function in vivo.Methods ES-2 cells were cultured and xenotransplanted into 36 nude mice,which were divided into 6 groups:normal saline (NS) group:NS 0.1 nd/day subcutaneous injection,and then NS 0.2 ml/week peritoneal injection; cisplatin (DDP) group:NS 0.1 ml/day subcutaneous injection,and then DDP 5 mg/kg ( diluted to 0.2 ml ) per week peritoneal injection; goserelin group:100 μg goserelin ( diluted to 0.1 ml) per day subcutaneous injection,and then NS 0.2 ml/week peritoneal injection; goserelin + DDP group:100 μg goserelin ( diluted to 0.1 ml) per day subcutaneous injection,and DDP 5 mg/kg (diluted to 0.2 ml) per week peritoneal injection; cetrorelix group:100 μg cetrorelix (diluted to 0.1 ml) per day subcutaneous injection and NS 0.2 ml/week peritoneal injection; cetrorelix + DDP group:100 μg cetrorelix (diluted to 0.1 ml) per day subcutaneous injection and DDP 5 mg/kg ( diluted to 0.2 ml) per week peritoneal injection.All the peritoneal injection started from subcutaneous injection one week later.To compare the weight of nude mice,the volumes of transplanted tumors,the expression of Ki-67 antigen in transplanted tumors,the estrus,the ratio of atretic follicles,the ratio of primary and preantral follicles,the levels of serum anti-Mullerian hormone ( AMH ),folliclestimulating hormone ( FSH),estradio ( E2 ) and progesterone (P) in each group.Results There were no significant difference in the weight of nude mice among 6 groups ( P ＞ 0.05 ),which on day 29 in NS group was ( 19.8 ±2.2) g,DDP group (20.5 ± 1.4) g,gosereline group ( 19.6 ±0.9) g,goserelin + DDP group ( 19.7 ± 1.6) g,cetrorelix group (20.7 ±2.2) g,and cetrorelix + DDP group ( 19.0 ± 1.7) g.The tumor volumes of different groups on the 12th day:NS group (241 ± 179) mm3,DDP group (78 ±20) mm3,gosereline group (78 t±55) mm3,goserelin + DDP group (64 ±48) mm3,cetrorelix group (78 ±64) mm3,or cetrorelix + DDP group (70 ± 19) mm3,in which there were significant difference between NS group and the other groups ( P ＜ 0.05 ) ; and the same result was obtained on day 15,19,22,26 and 29 ( P ＜ 0.05 ).The expression of Ki-67 in NS group was ( 33 ± 10 ) ％,in which it was higher than those in DDP group 3.5％,goserelin group 8.8％,goserelin + DDP group 1.5％,cetrorelix group (23 ± 11 ) ％,or cetrorelix + DDP group ( 8 ± 6 ) ％ ( P ＜ 0.05 ).The ratio of primary and preantral follicles in goserehn group was (71.5 ± 8.1 ) ％,in goserelin + DDP group was (62.4 ± 4.1 ) ％,in cetrorelix group was (71.2 ± 7.4) ％,and in cetrorelix + DDP group was (63.8 ±3.1 )％,in which they were much higher than that in DDP group ( 47.0 ± 4.8 ) ％ ( P ＜ 0.05 ).The level of AMH in goserelin group was ( 98 ± 27 ) ng/ml,which was much higher than that in NS group (66.2 ± 17.4) ng/ml (P ＜0.05),while there were no difference in the levelsof FSH,E2 or P among different groups ( P ＞ 0.05).Conclusion GnRH analogues could inhibit the growth of transplanted tumors in nude mice,meanwhile increase the secretion of AMH,decrease the frequencies and prolong the lasting time of estrus,decrease the ratio of atretic follicles,raise the ratio of primary and preantral follicles,which may be protect the ovarian function of nude mice.
