多囊卵巢综合征大鼠子宫内膜细胞凋亡及VEGF-A的表达
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摘要
目的:观察多囊卵巢综合征(PCOS)大鼠子宫内膜细胞的凋亡情况以及VEGF-A的表达变化,探讨细胞凋亡及VEGF-A在PCOS子宫内膜发生功能失常的过程中的作用.方法:大鼠皮下注射硫酸普拉睾酮钠来构建PCOS模型,TUNEL法检测大鼠子宫内膜细胞凋亡情况、免疫组织化学法和蛋白质免疫印迹法检测VEGF-A在大鼠子宫内膜中的表达情况.结果:TUNEL结果显示PCOS组大鼠子宫内膜细胞凋亡率较对照组明显降低(P <0. 05);免疫组织化学结果显示VEGF-A在PCOS组大鼠子宫内膜腺上皮细胞中的表达较对照组明显减弱(P <0. 05);蛋白质免疫印迹分析显示PCOS组大鼠子宫中VEGF-A蛋白的表达较正常对照组明显降低(P <0. 05).结论:PCOS子宫内膜功能失常可能与子宫内膜细胞凋亡减少有关,VEGF-A表达下调可能是PCOS子宫内膜增生过度的一种代偿性作用.
Objective: To observe the apoptosis of endometrial cells and the expression of VEGF-A in rats with polycystic ovary syndrome( PCOS),and to explore the role of apoptosis and VEGF-A in the process endometrial dysfunction in PCOS. Methods: PCOS model was established by subcutaneous injection of sodium prandrosterone sulfate sodium in rats. TUNEL assay was used to detect the apoptosis of rat endometrial cells. Immunohistochemistry and Western blotting were used to detect the expression of VEGF-A in rat endometrium. Results: TUNEL results showed that the apoptosis rate of endometrial cells in PCOS group was significantly lower than that in control group( P < 0. 05). Immunohistochemistry results showed that the expression of VEGF-A in the endometrial glandular epithelial cells of PCOS group was significantly weaker than that of the control group( P < 0. 05). Western blot analysis showed that the expression of VEGF-A protein in uterus of PCOS group was significantly lower than that of normal control group( P < 0. 05). Conclusion: Endometrial dysfunction in PCOS may be related to the decrease of endometrial cell apoptosis. Down-regulation of VEGF-A expression may be a compensatory effect of endometrial hyperplasia in PCOS.
Objective: To observe the apoptosis of endometrial cells and the expression of VEGF-A in rats with polycystic ovary syndrome( PCOS),and to explore the role of apoptosis and VEGF-A in the process endometrial dysfunction in PCOS. Methods: PCOS model was established by subcutaneous injection of sodium prandrosterone sulfate sodium in rats. TUNEL assay was used to detect the apoptosis of rat endometrial cells. Immunohistochemistry and Western blotting were used to detect the expression of VEGF-A in rat endometrium. Results: TUNEL results showed that the apoptosis rate of endometrial cells in PCOS group was significantly lower than that in control group( P < 0. 05). Immunohistochemistry results showed that the expression of VEGF-A in the endometrial glandular epithelial cells of PCOS group was significantly weaker than that of the control group( P < 0. 05). Western blot analysis showed that the expression of VEGF-A protein in uterus of PCOS group was significantly lower than that of normal control group( P < 0. 05). Conclusion: Endometrial dysfunction in PCOS may be related to the decrease of endometrial cell apoptosis. Down-regulation of VEGF-A expression may be a compensatory effect of endometrial hyperplasia in PCOS.
引文
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[17] GORDON L K,KIYOHARA M,FU M,et al. EMP2regulates angiogenesis in endometrial cancer cells through induction of VEGF[J]. Oncogene,2013,32(46):5369-5376.
[2] HAOULA Z,SALMAN M. Evaluating the association between endometrial cancer and polycystic ovary syndrome[J]. Hum Reprod,2012,27(5):1327-1331.
[3] HOPWOOD D. Atrophy and apoptosis in the cyclical human endometrium[J]. J Pathol,1976,119(3):159-166.
[4]刘小惠,吴小华.血管内皮生长因子在女性生殖生理和病理中的研究进展[J].现代妇产科进展,2017,26(3):231-234.LIU X H, WU X H. Research progress of vascular endothelial growth factor in female reproductive physiology and pathology[J]. Progress in Modern Obstetrics and Gynecology,2017,26(3):231-234.
[5] KUYUCU Y,CELIK LS,KENDIRLINANO,et al.Investigation of the uterine structural changes in the experimental model with polycystic ovary syndrome and effects of vitamin D treatment:An ultrastructural and immunohistochemical study[J]. Reprod Biol,2018,18(1):53-59.
[6]姜晓琳,张立德,滕飞,等.二甲双胍联合膈下逐瘀汤对多囊卵巢综合征胰岛素抵抗大鼠TLR4/NF-κB信号通路的影响[J].中国病理生理杂志,2018(1):158-162.JIANG X L,ZHANG L D,TENG F,et al. Effects of metformin combined with Qixiazhuyu decoction on TLR4/NF-κB signaling pathway in insulin resistance rats with polycystic ovary syndrome[J]. Chinese Journal of Pathophysiology,2018(1):158-162.
[7]李小芳,李秀莹,林辉瑞,等.多囊卵巢综合征相关子宫内膜增生病变的研究进展[J].中华妇幼临床医学杂志(电子版),2018,14(4):104-110.LI X F,LI X Y,LIN H R,et al. Progress in the study of endometrial hyperplasia associated with polycystic ovary syndrome[J]. Chinese Journal of Women and Children Clinical Medicine(Electronic edition),2018,14(4):104-110.
[8] INDHAVIVADHANA S,RATTANACHAIYANONT M,WONGWANANURUK T,et al. Endometrial neoplasia in reproductive-aged Thai women with polycystic ovary syndrome[J] Int J Gynaecol Obstet,2018,142(2):170-175.
[9] ZHAO P L,ZHANG Q F,YAN L Y,et al. Functional investigation on aromatase in endometrial hyperplasia in polycystic ovary syndrome cases[J]. Asian Pac J Cancer Prev,2014,15(20):8975-8979.
[10] MITSUHASHI A,UEHARA T,HANAWA S. Prospective evaluation of abnormal glucose metabolism and insulin resistance in patients with atypical endometrial hyperplasia and endometrial cancer[J]. Support Care Cancer,2017,25(5):1495-1501.
[11] ANAGNOSTIS P,TARLATZIS BC,KAUFFMAN RP,et al. Polycystic ovaria syndrome(PCOS):long-term metabolic consequences[J]. Metabolism, 2017,doi:S0026-0495(17)30274-30273.
[12] LEE D E,PARK S Y,et al. Clinical and biochemical profiles according to homeostasis model assessmentinsulin resistance(HOMA-IR)in Korean women with polycytistic ovary syndrome[J]. J Menopausal Med,2014,20(3):104-110.
[13] TANIGUCHI F,KAPONIS A,IZAWA M,et al. Apoptosis and endometriosis[J]. Frontiers In Bioscience,2011,3:648-662.
[14] YIN D,WANG N,ZHANG S L,et al. Specific siRNA inhibits XIAP expression in human endometrial carcinoma cell apoptosis[J]. Cell Biochem Biophys,2015,71(1):161-165.
[15] JIN A,CHEN H,WANG C,et al. Elevated expression of CD147 in patients with endometriosis and its role in regulating apoptosis and migration of human endometrial cells[J]. Fertil Steril,2014,101(6):1681-1687.
[16] QIN Y,SEAGER M,OSMAN A,et al. Ovarian VEGF(165)b expression regulates follicular development,corpus luteum function and fertility.[J]. Reproduction,2012,143(4):501-511.
[17] GORDON L K,KIYOHARA M,FU M,et al. EMP2regulates angiogenesis in endometrial cancer cells through induction of VEGF[J]. Oncogene,2013,32(46):5369-5376.