高压氧暴露对慢性应激所致卵巢功能减退模型大鼠的激素水平和TGF-β1,Smad3表达影响
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摘要
目的探讨高压氧(hyperbaric oxygen,HBO)暴露对慢性应激所致卵巢功能减退(diminished ovarian reserve,DOR)大鼠激素水平和转化生长因子β1(transforming growth factor beta 1,TGF-β1)、Smad3表达影响,探究其治疗机制。方法雌性大鼠应激造模成功后随机分为3组各10只:模型组、自然恢复组和HBO组,另取空白组10只。自然恢复组、HBO组予不同干预后,分别记录大鼠动情周期、卵巢指数、激素水平、卵巢组织TGF-β1、Smad3蛋白相对表达,观察卵巢显微结构,进行组间比较。结果 HBO组动情周期恢复时间短于自然恢复组;模型组卵巢指数、雌二醇(estradiol, E2)激素水平、TGF-β1、Smad3蛋白相对表达量均明显低于空白组、自然恢复组、HBO组(P<0.01或0.05);模型组黄体生成素(luteinizing hormone,LH)、卵泡刺激素(follicle stimulating hormone, FSH)激素水平均明显高于空白组、自然恢复组、HBO组(P<0.01或0.05)。显微结构显示:HBO组卵泡生长活跃,各级卵泡明显增多,闭锁卵泡明显减少。结论 HBO暴露能明显促进慢性应激所致DOR大鼠TGF-β1/Smad3信号通路的传导,促进卵巢各级卵泡分化与增殖,提高激素水平,进而恢复卵巢功能。
Objective To research the effect of hyperbaric oxygen(HBO) exposure on hormone level and transforming growth factor beta 1(TGF-β1),Smad3 protein expression in chronic stress-induced diminished ovarian reserve model rats,and explore its possible therapeutic mechanism. Methods Female rats were randomly divided into model group,natural recovery group and HBO group after chronic multiple psychological stressors. Another 10 rats were taken from the blank group. The natural recovery group and the HBO group were respectively given different interventions. Rats estrus cycle,ovary index,ovarian microstructure,hormone level and protein expression of TGF-β1,Smad3 in ovarian tissue were respectively recorded. Results HBO therapy obviously promoted the recovery of estrus cycle. The ovary index,estradiol(E2) and protein expression levels of TGF-β1,Smad3 in model group were significantly lower than those in blank group,natural recovery group and HBO group(P<0.01 or 0.05).The luteinizing hormone(LH), follicle stimulating hormone(FSH) expression levels in model group were significantly higher than those in blank group,natural recovery group and HBO group(P<0.01 or 0.05). The microstructure showed that the follicle of HBO group was active, the follicles at all levels were increased obviously, and atresia follicles were markedly reduced. Conclusion HBO can significantly promote TGF-β1/Smad3 signalling pathway to promote the proliferation and differentiation of granular cell, to improve hormone levels and then restore ovarian function.
Objective To research the effect of hyperbaric oxygen(HBO) exposure on hormone level and transforming growth factor beta 1(TGF-β1),Smad3 protein expression in chronic stress-induced diminished ovarian reserve model rats,and explore its possible therapeutic mechanism. Methods Female rats were randomly divided into model group,natural recovery group and HBO group after chronic multiple psychological stressors. Another 10 rats were taken from the blank group. The natural recovery group and the HBO group were respectively given different interventions. Rats estrus cycle,ovary index,ovarian microstructure,hormone level and protein expression of TGF-β1,Smad3 in ovarian tissue were respectively recorded. Results HBO therapy obviously promoted the recovery of estrus cycle. The ovary index,estradiol(E2) and protein expression levels of TGF-β1,Smad3 in model group were significantly lower than those in blank group,natural recovery group and HBO group(P<0.01 or 0.05).The luteinizing hormone(LH), follicle stimulating hormone(FSH) expression levels in model group were significantly higher than those in blank group,natural recovery group and HBO group(P<0.01 or 0.05). The microstructure showed that the follicle of HBO group was active, the follicles at all levels were increased obviously, and atresia follicles were markedly reduced. Conclusion HBO can significantly promote TGF-β1/Smad3 signalling pathway to promote the proliferation and differentiation of granular cell, to improve hormone levels and then restore ovarian function.
引文
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[15] Celik H,Bildircin D,Guven D,et al.Random anti-Müllerian hormone predicts ovarian response in women with high baseline follicle-stimulating hormone levels:anti-Müllerian hormone in poor responders in assisted reproductive treatment[J].J Assist Reprod Genet,2012,29(8):797-802
[16] 周敏,冯强,黄丽波,等.转化生长因子TGF-β/Smads信号传导通路在哺乳动物卵巢发育中的调控作用及其作用机制[J].动物营养学报,2017,29(7):2283-2288
[17] Sasseville M,Ritter LJ,Nguyen TM,et al.Growth differentiation factor 9 signaling requires ERK1 / 2 activity in mouse granulosa and cumulus cell[J].J Cell Sci,2010,123(Pt 18):3166-3176
[18] Kaplan ST,Hemsinli D,Kaplan S,et al.Amputation predictors in diabetic foot ulcers treated with hyperbaric oxygen[J].J Wound Care,2017,26(7):361-366
[19] Cui HJ,He HY,Yang AL,et al.Hyperbaric oxygen for experimental intracerebral haemorrhage:systematic review and stratified meta-analysis[J].Brain Inj,2017,31(4):456-465
[2] 申可佳,申奏秦旋,刘碧源,等.慢性制动应激建立卵巢早衰及卵巢低反应小鼠模型的研究[J].中国医药导报,2017,14(17):19-22
[3] 刘碧源,申可佳,申奏秦旋,等.护卵汤对慢性应激超排卵小鼠卵巢 TGF-β1,P-Smad3及FSHR mRNA表达的影响[J].湖南中医药大学学报,2017,37(11):1192-1195
[4] Divyashree S,Yajurvedi HN.Long-term chronic stress exposure induces PCO phenotype in rat[J].Reproduction,2016,152(6):765-774
[5] Kala M,Nivsarkar M.Role of cortisol and superoxide dismutase in psychological stress induced anovulation[J].Gen Comp Endocrinol,2015,225:117-124
[6] European Society for Human Reproduction and Embryology (ESHRE) Guideline Group on POI,Webber L,Davies M,et al.ESHRE Guideline:management of women with premature ovarian insufficiency[J].Hum Reprod,2016,31(5):926-937
[7] 张秀,鲁雅,王佩娟,等.卵巢早衰的病因研究进展[J].湖北中医药大学学报,2017,19(1):118-120
[8] 王灿,廖海燕,刘慧萍,等.自噬机制与卵巢早衰的关系[J].生殖与避孕,2016,36(8):637-641
[9] 黄雪君,孙冬梅,陈玉兴,等.护卵颗粒对重复制动应激致卵巢功能减退模型大鼠的影响[J].世界中医药,2016,11(3):502-506
[10] Gao Y,Chen F,Kong QQ,et al.Stresses on female mice impair oocyte developmental potential[J].Reprod Sci,2016,23(9):1148-1157
[11] Yuan HJ,Han X,He N,et al.Glucocorticoids impair oocyte developmental potential by triggering apoptosis of ovarian cells via activating the Fas system[J].Sci Rep,2016,6:24036
[12] Bronzi CD,Orozco AS,Rodriguez D,et al.Noradrenaline modulates the presence of gonadotropin releasing hormone in ovary.The importance of its interrelation on the ovarian steroidogenesis and apoptosis on dioestrus Ⅱ in rat[J].J steroid Biochem Mol Biol,2015,154:39-46
[13] Kuo FT,Fan K,Ambartsumyan G,et al.Relative expression of genes encoding SMAD signal transduction factors in human granulosa cells is correlated with oocyte quality[J].J Asset Reprod Genet,2011,28(10):931-938
[14] Li X,Tripurani SK,James R,et al.Minimal fertility defects in mice deficient in oocyte- expressed Smad4[J].Biol Reprod,2012,86(1):1-6
[15] Celik H,Bildircin D,Guven D,et al.Random anti-Müllerian hormone predicts ovarian response in women with high baseline follicle-stimulating hormone levels:anti-Müllerian hormone in poor responders in assisted reproductive treatment[J].J Assist Reprod Genet,2012,29(8):797-802
[16] 周敏,冯强,黄丽波,等.转化生长因子TGF-β/Smads信号传导通路在哺乳动物卵巢发育中的调控作用及其作用机制[J].动物营养学报,2017,29(7):2283-2288
[17] Sasseville M,Ritter LJ,Nguyen TM,et al.Growth differentiation factor 9 signaling requires ERK1 / 2 activity in mouse granulosa and cumulus cell[J].J Cell Sci,2010,123(Pt 18):3166-3176
[18] Kaplan ST,Hemsinli D,Kaplan S,et al.Amputation predictors in diabetic foot ulcers treated with hyperbaric oxygen[J].J Wound Care,2017,26(7):361-366
[19] Cui HJ,He HY,Yang AL,et al.Hyperbaric oxygen for experimental intracerebral haemorrhage:systematic review and stratified meta-analysis[J].Brain Inj,2017,31(4):456-465