The inhibitory effects of vascular endothelial growth factor antisense gene on experimental endometriosis in rats

In: Chung-Hua Fu Ch'an K'o Tsa Chih · 2007 · vol. 3(1) , pp. 13–15 · doi:10.3877/cma.j.issn.1673-5250.2007.01.105 · W3029592982
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VEGF antisense ODNs significantly reduced endometriosis transplant volume and induced regression in rats without impacting ovarian function.

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This study investigated the therapeutic potential of vascular endothelial growth factor (VEGF) antisense oligonucleotides in a surgically induced rat model of endometriosis. Researchers treated rats with VEGF antisense, sense, missense oligonucleotides, or saline via intraperitoneal injection over four weeks and subsequently measured implant volume and histological changes. The results demonstrated that VEGF antisense treatment significantly reduced the volume of ectopic endometrial implants and induced marked regression of epithelial and stromal components compared to control groups. Importantly, the treatment did not adversely affect ovarian function or serum hormone levels, indicating a specific inhibitory effect on lesion growth without systemic hormonal disruption. This paper is centrally about endometriosis — specifically experimental inhibition of ectopic endometrial growth using anti-angiogenic gene therapy in an animal model.

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Abstract

Objective To investigate whether vascular endothelial growth factor (VEGF) antisense ODNs can prevent endometrial implantation in a rat model. Methods 32 rats models of surgically induced endometriosis were averagely divided into 4 groups (A, B, C, D group). The rats were treated with2 000 μmol/100 μl VEGF antisense, sense, missense ODNs or saline 100 μl by injection into the abdomen respectively every 2 days for 4 weeks. the rats were killed at 2 weeks after the therapy was finished. The rate of transplantation inhibition was calculated by the formula (1 — V2/V1) × 100%. Vaginal cytology smears were examined everyday to determine the rats' estrus cycle, endometrium transplant, normal endometrium and ovary were resected for histological examination, and serum E2, P level were detected by radioimmunoassay method. Results Transplants volum of VEGF antisense ODNs treated rats (A group)was diminuted significantly compared with other 3 groups (P<0. 01), the rate of transplantation inhibition of VEGF antisense ODNs group (A group) was much higher than other 3 groups (P<0. 01). Transplants of VEGF antisense ODNs treated rats (A group) showed marked regression of both epithelial and stromal components, epithelium developed poorly, lamina propria was thinner with much fewer stromal cells and glands. The ovary function and the structure of the normal endometrium were not affected by VEGF antisense ODNs, nearly all rats showed normal estrus cycle, no significant difference of serum E2, P level was found among 4 groups. Conclusion VEGF antisense ODNs could inhibit the growth and induce the regression of explants in a rat endometriosis model without affecting the ovary function. Key words: endometriosis; vascular endothelial growth factor (VEGF); antisense ODNs; rat
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Objective

To investigate whether vascular endothelial growth factor (VEGF) antisense ODNs can prevent endometrial implantation in a rat model.

Methods

32 rats models of surgically induced endometriosis were averagely divided into 4 groups (A, B, C, D group). The rats were treated with2 000 μmol/100 μl VEGF antisense, sense, missense ODNs or saline 100 μl by injection into the abdomen respectively every 2 days for 4 weeks. the rats were killed at 2 weeks after the therapy was finished. The rate of transplantation inhibition was calculated by the formula (1 — V2/V1) × 100%. Vaginal cytology smears were examined everyday to determine the rats' estrus cycle, endometrium transplant, normal endometrium and ovary were resected for histological examination, and serum E2, P level were detected by radioimmunoassay method.

Results

Transplants volum of VEGF antisense ODNs treated rats (A group)was diminuted significantly compared with other 3 groups (P<0. 01), the rate of transplantation inhibition of VEGF antisense ODNs group (A group) was much higher than other 3 groups (P<0. 01). Transplants of VEGF antisense ODNs treated rats (A group) showed marked regression of both epithelial and stromal components, epithelium developed poorly, lamina propria was thinner with much fewer stromal cells and glands. The ovary function and the structure of the normal endometrium were not affected by VEGF antisense ODNs, nearly all rats showed normal estrus cycle, no significant difference of serum E2, P level was found among 4 groups.

Conclusion

VEGF antisense ODNs could inhibit the growth and induce the regression of explants in a rat endometriosis model without affecting the ovary function. | 1 Jones RC. The effect of a luteinizing hormone releasing hormone (LRH) agonist ( Wy-40, 972),levonorgestrel,danazol and ovariectomy on experimental endometriosis in the rat. Acta Endocrinol (Copenh),1984,106 (2) :282-288. | | | 2 Mclaren J, Prentice A, Charnock-Jones DS, et al . Vascular endothelial growth factors (VEGF)concentrations are elevated in peritoneal fluid of women with endometriosis. Hum Reprod, 1996,11(1):220-223. | | | 3 Nisolle M,Casanas-Roux F, Anaf V, et al. Morphometric study of the stromal vascularisation in peritoneal endometriosis. Fertil Steril, 1993,59(3):681-684. | | | 4 Donnez J, Smoes P,Gillerot S, et al. Vascular endothelial growthfactors (VEGF) in endometriosis. Hum Reprod, 1998,13(6):1686-1690. | | | 5 Hull ML, Charnock-Jones DS, Chan CL, et al. Antiangiogenic agents are effective inhibitors of endometriosis. J Clin Endocrinol Metab, 2003,88(6):2889-2899. | | | 6 Weintraub HM. Antisense RNA and DNA. Sci Am, 1990,262(1):40-46. | | | 7 Stein CA,Cheng YC. Antisense oligonucleotides as therapeuticagents is the bullet really magical? Science, 1993,261(5124):1004-1012. | | | 8 任正刚,金由辛,薛琼等.血管内皮生长因子反义寡核苷酸抑制裸鼠人肝癌模型的作用观察.中华医学杂志,1999,79(1):65-66. | | [1] | 刘思锐, 赵辰阳, 张睿, 张一休, 杨萌. 多普勒超声对孕鼠子宫动脉不同节段血流动力学参数的评估[J/OL]. 中华医学超声杂志(电子版), 2024, 21(09): 877-883. | | [2] | 林琳, 田思萌, 于永华, 徐飞飞, 黄明莉. 干细胞及其外泌体治疗宫腔黏连的研究现状[J/OL]. 中华妇幼临床医学杂志(电子版), 2024, 20(03): 271-275. | | [3] | 邵小丽, 林燕, 张玲玲, 韩亚琴. 超声引导下子宫肌瘤注射聚桂醇硬化术联合术后米非司酮治疗临床疗效分析[J/OL]. 中华妇幼临床医学杂志(电子版), 2024, 20(03): 353-360. | | [4] | 乔林. 子宫内膜异位症鉴别诊断病例分享[J/OL]. 中华妇幼临床医学杂志(电子版), 2024, 20(02): 248-. | | [5] | 杨文飞, 郝嘉文, 鲁梦远, 赵学刚, 李聪颖, 盖晨阳, 张晶, 张庆富. 高压电烧伤对大鼠心肌氧化应激的影响及N-乙酰半胱氨酸的干预作用[J/OL]. 中华损伤与修复杂志(电子版), 2024, 19(02): 106-112. | | [6] | 黄福, 王黔, 金相任, 唐云川. VEGFR2、miR-27a-5p在胃癌组织中的表达与临床病理参数及预后的关系研究[J/OL]. 中华普外科手术学杂志(电子版), 2024, 18(05): 558-561. | | [7] | 张礼刚, 邹志辉, 许顺, 蔡可可, 胡永涛, 梁朝朝. 酒精对慢性非细菌性前列腺炎中T淋巴细胞变化的影响研究[J/OL]. 中华腔镜泌尿外科杂志(电子版), 2024, 18(01): 74-81. | | [8] | 朱佳琳, 方向, 贵诗雨, 黄丹, 周小雨, 郭文恺. 大鼠切口疝腹膜前间隙补片修补术后血清中VEGF 和Ang-1 的表达情况[J/OL]. 中华疝和腹壁外科杂志(电子版), 2024, 18(06): 703-707. | | [9] | 赛甫丁·艾比布拉, 买买提·依斯热依力, 李义亮, 王永康, 王志, 克力木·阿不都热依木. 不同材质补片修补对腹壁疝大鼠腹横筋膜组织转化生长因子-β1及Collagen合成代谢的作用[J/OL]. 中华疝和腹壁外科杂志(电子版), 2024, 18(02): 161-167. | | [10] | 张敏龙, 杨翠平, 王博, 崔云杰, 金发光. MiR-200b-3p 通过抑制HIF-1α 表达减轻海水吸入诱导的肺水肿作用及机制[J/OL]. 中华肺部疾病杂志(电子版), 2024, 17(05): 696-700. | | [11] | 刘锦程, 王斌, 张雯, 张明周, 刘禹, 叶东樊, 黄赞胜, 邱凌霄, 卿斌, 王创业, 王南博, 王苹, 郭宇航, 周培花, 程秋霞, 徐智. 肺泡灌洗液RASSF1A及SHOX2甲基化联合径向超声特征对肺结节性质鉴别诊断的意义[J/OL]. 中华肺部疾病杂志(电子版), 2024, 17(04): 505-511. | | [12] | 胡启明, 鄢潇, 尤志学, 黄骁昊. 经瘢痕处单孔腹腔镜下切除多病灶腹壁子宫内膜异位症[J/OL]. 中华腔镜外科杂志(电子版), 2024, 17(05): 314-317. | | [13] | 张蕾, 彭超, 周应芳. 直肠阴道隔子宫内膜异位症腹腔镜手术技巧[J/OL]. 中华腔镜外科杂志(电子版), 2024, 17(05): 257-261. | | [14] | 芦煜, 李振宇, 吴承东, 周仲伍. 肛周子宫内膜异位症一例报告[J/OL]. 中华结直肠疾病电子杂志, 2024, 13(05): 431-434. | | [15] | 洪凡, 陈敦金, 傅洋, 梁新月, 吴毅, 王晓怡. 体外受精-胚胎移植妊娠合并前置胎盘临床研究[J/OL]. 中华产科急救电子杂志, 2024, 13(03): 176-182. | | 阅读次数 | ||||| | 全文 | | |||| | 摘要 | | |||| 版权所有 中华医学会 中华医学电子音像出版社有限责任公司 京ICP备14006079号-1 网络出版服务许可证:(署)网出证(京)字第075号 AI 小 编 AI小编

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