补肾中药对多囊卵巢综合征卵泡抑素的影响和机理探讨
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摘要
目的:探讨卵泡抑素在多囊卵巢综合征中的发病机制,观察补肾药物对卵泡抑素的调节作用,进一步丰富肾主生殖理论的研究。
方法:临床研究对符合纳入标准的40例行IVF-ET的肾虚型PCOS患者进行临床观察,分为中西药组和西药组,分别对两组患者的中医肾虚证候评分变化、取卵日卵泡液FS含量、取卵数、优质卵率等指标进行评定,并观察与FS的关系。实验研究选择硫酸普拉睾酮钠造模法对大鼠进行PCOS造模,30只大鼠随机分为正常组、模型组、中西药组。观察三组的阴道涂片、子宫、卵巢指数、子宫、卵巢组织形态学、血清FS及组织FSmRNA含量变化,探讨补肾中药治疗PCOS的作用机理。
结果:肾虚型PCOS患者IVF-ET降调节后主要表现为肾虚证,以肾阴虚为主,中西药物联合应用方案与单用西药方案比较,在不影响临床诱导排卵疗效的前提下,可明显改善降调节后患者肾虚症状,通过对卵泡液中FS的调控,提高卵细胞质量。PCOS模型组大鼠阴道涂片提示无排卵,见卵巢呈囊状,有早期发育的较多的小卵泡及闭锁卵泡,大鼠卵巢内FSmRNA表达增多,循环FS增多,二至天癸颗粒可以调节FSmRNA的表达,减少血清FS含量,促进成熟卵泡的产生,提高卵细胞质量。
结论:本课题研究发现,肾阴亏虚是PCOS患者IVF-ET超促排卵降调节后的主导病机。二至天癸颗粒在保证临床促排卵疗效的前提下,改善肾虚症状,提高卵细胞质量,其可能的机理包括:改善控制性超排卵周期生殖内分泌激素环境;调控卵泡液FS含量;改善PCOS大鼠卵巢组织形态学,并通过降低PCOS大鼠FSmRNA的表达,减少血清FS含量,促进卵泡的发育,提高卵细胞质量。补肾中药能够在基因水平发挥整体调节之优势,改善卵泡机能的旁分泌和自分泌的微环境,与外源性性激素协同作用,重建生殖内分泌环境的平衡,从一个侧面反映传统的中医调经种子理论在辅助生殖技术中的指导价值。
Objective:To explore the pathogenesis of FS in PCOS and regulation of FS by kidney-reinforcing drugs, futher enrich the theory of kidney dominating reproduction..
Methods: Fourty infertile patients with PCOS undergoing IVF-ET were divided into two groups, 20 cases in the study group treated with Erzhi Tiangui Granules and western medicine, and the other 20 cases in the control group were treated with gonadotropin- releasing hormone agonist (GnRH-a) and gonadotropin (Gn) alone. The long term protocol was adopted. The expression of FS in follicular fluid on the day of retrieving oocytes were detected by ELISA, and symptom scores, number of retrieved oocytes were evaluated and evalute the relation between FS and these indexes. Thirty mice were allocated into three groups randomly in experimental research,①normal group: performed hypodermic injection with sterile water for injection usp of same volume as model group and study group on the same time schedule;②model group:performed hypodermic injection with Sodium prasterone sulfate, 9mg/100g weight③study group:the same volume of Sodium prasterone sulfate were given; 10 days later, Erzhi Tiangui Granules were given to study group by gastric perfusion . The other two groups were given same volume salt solution. other 10 days later, all mice were killed. Their vaginal smears, uterus index and overy index, histomorphology of uterus and overy ,serum FS,tissue FSmRNA were observed。
Results: Kidney yin deficiency were presentated in PCOS patients of IVF-ET, Symptoms of Shenxu in study group had been significantly improved because of kidney-reinforcing drugs. The drugs regulated serum FS,improve,oocyte quality,promoting oocyte maturation. Vaginal smears of the model mice suggested anovulation, their ovary were cystic and small follicle sand atretic follicles were showed. FSmRNA of overy were increased, serum FS also increased. Erzhi Tiangui Granules can regulated FSmRNA, decreased serum FS,promote the mammalian follicular development .
Conclusion: The leading mechanism of PCOS patients is insufficient of kidney Yin after down regulation in controlled ovarian hyperstimulation while kidney-reinforcing drugs correct the imbalance state and promote oocyte quality . The possible mechanism of combined therapy is that:①Promoting oocyte maturation by regulating the level FSmRNA expression in overy;②Balancing the paracrine and autocrine of follicular function. Kidney-reinforcing drugs play its role on genic level therapy,reflectded the value of TCM Theory.
方法:临床研究对符合纳入标准的40例行IVF-ET的肾虚型PCOS患者进行临床观察,分为中西药组和西药组,分别对两组患者的中医肾虚证候评分变化、取卵日卵泡液FS含量、取卵数、优质卵率等指标进行评定,并观察与FS的关系。实验研究选择硫酸普拉睾酮钠造模法对大鼠进行PCOS造模,30只大鼠随机分为正常组、模型组、中西药组。观察三组的阴道涂片、子宫、卵巢指数、子宫、卵巢组织形态学、血清FS及组织FSmRNA含量变化,探讨补肾中药治疗PCOS的作用机理。
结果:肾虚型PCOS患者IVF-ET降调节后主要表现为肾虚证,以肾阴虚为主,中西药物联合应用方案与单用西药方案比较,在不影响临床诱导排卵疗效的前提下,可明显改善降调节后患者肾虚症状,通过对卵泡液中FS的调控,提高卵细胞质量。PCOS模型组大鼠阴道涂片提示无排卵,见卵巢呈囊状,有早期发育的较多的小卵泡及闭锁卵泡,大鼠卵巢内FSmRNA表达增多,循环FS增多,二至天癸颗粒可以调节FSmRNA的表达,减少血清FS含量,促进成熟卵泡的产生,提高卵细胞质量。
结论:本课题研究发现,肾阴亏虚是PCOS患者IVF-ET超促排卵降调节后的主导病机。二至天癸颗粒在保证临床促排卵疗效的前提下,改善肾虚症状,提高卵细胞质量,其可能的机理包括:改善控制性超排卵周期生殖内分泌激素环境;调控卵泡液FS含量;改善PCOS大鼠卵巢组织形态学,并通过降低PCOS大鼠FSmRNA的表达,减少血清FS含量,促进卵泡的发育,提高卵细胞质量。补肾中药能够在基因水平发挥整体调节之优势,改善卵泡机能的旁分泌和自分泌的微环境,与外源性性激素协同作用,重建生殖内分泌环境的平衡,从一个侧面反映传统的中医调经种子理论在辅助生殖技术中的指导价值。
Objective:To explore the pathogenesis of FS in PCOS and regulation of FS by kidney-reinforcing drugs, futher enrich the theory of kidney dominating reproduction..
Methods: Fourty infertile patients with PCOS undergoing IVF-ET were divided into two groups, 20 cases in the study group treated with Erzhi Tiangui Granules and western medicine, and the other 20 cases in the control group were treated with gonadotropin- releasing hormone agonist (GnRH-a) and gonadotropin (Gn) alone. The long term protocol was adopted. The expression of FS in follicular fluid on the day of retrieving oocytes were detected by ELISA, and symptom scores, number of retrieved oocytes were evaluated and evalute the relation between FS and these indexes. Thirty mice were allocated into three groups randomly in experimental research,①normal group: performed hypodermic injection with sterile water for injection usp of same volume as model group and study group on the same time schedule;②model group:performed hypodermic injection with Sodium prasterone sulfate, 9mg/100g weight③study group:the same volume of Sodium prasterone sulfate were given; 10 days later, Erzhi Tiangui Granules were given to study group by gastric perfusion . The other two groups were given same volume salt solution. other 10 days later, all mice were killed. Their vaginal smears, uterus index and overy index, histomorphology of uterus and overy ,serum FS,tissue FSmRNA were observed。
Results: Kidney yin deficiency were presentated in PCOS patients of IVF-ET, Symptoms of Shenxu in study group had been significantly improved because of kidney-reinforcing drugs. The drugs regulated serum FS,improve,oocyte quality,promoting oocyte maturation. Vaginal smears of the model mice suggested anovulation, their ovary were cystic and small follicle sand atretic follicles were showed. FSmRNA of overy were increased, serum FS also increased. Erzhi Tiangui Granules can regulated FSmRNA, decreased serum FS,promote the mammalian follicular development .
Conclusion: The leading mechanism of PCOS patients is insufficient of kidney Yin after down regulation in controlled ovarian hyperstimulation while kidney-reinforcing drugs correct the imbalance state and promote oocyte quality . The possible mechanism of combined therapy is that:①Promoting oocyte maturation by regulating the level FSmRNA expression in overy;②Balancing the paracrine and autocrine of follicular function. Kidney-reinforcing drugs play its role on genic level therapy,reflectded the value of TCM Theory.
引文
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