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卵巢胰岛素抵抗对卵巢糖代谢及功能影响的实验研究
  • ISSN号:0376-2491
  • 期刊名称:《中华医学杂志》
  • 时间:0
  • 分类:R587.1[医药卫生—内分泌;医药卫生—临床医学;医药卫生—内科学] R714.256[医药卫生—妇产科学;医药卫生—临床医学]
  • 作者机构:[1]黑龙汀中医药大学附属第一医院妇产科,哈尔滨150040
  • 相关基金:国家自然科学基金(30572404);黑龙江省杰出青年基金(JC200804);国家中医临床研究基地资助
中文摘要:

目的探讨卵巢内胰岛素信号分子缺失对卵巢自身功能影响,为阐明卵巢局部胰岛素抵抗对生殖功能作用提供理论支撑。方法(1)分别选择蛋白激酶B2(AKT2)基因缺失的(AKT2-)和其同窝出生的有完整AKT2基因(AKT2+)的雌性小鼠评估卯巢糖摄取情况,并进行卵巢交互移植,构建AKT2基因型组合个体分别为A组(躯体+,卵巢+)12只,B组(躯体+,卵巢-)15只,C组(躯体-,卵巢+)8只。(2)监测动情周期,随机分组,对刺激组小鼠采用卵泡刺激素(0.75IU/g)进行干预后取材。评估各组小鼠卵巢组织形态与生殖激素指标,并且采用RT-PCR检测卵巢内胰岛素信号分子和甾体激素合成酶的表达。结果(1)AKT2-卵巢的葡萄糖摄取能力显著下降。(2)B组动情周期显著延长,卵巢内黄体数量明显减少,而卵泡的数量明显增多,同时17一OH和T的水平显著升高。(3)基础状态下,B组卵巢内ERK-1和CYP17的表达明显增强。刺激状态下,B组卵巢内ERK-1、CYP17、CYP19和GSK3B均显著升高。结论(1)AKT2-小鼠卵巢存在胰岛素抵抗,出现动情周期延长,卵巢多囊性改变和雄激素及其合成酶水平增高,类似PCOS表现。(2)卵巢局部胰岛素抵抗使卵巢自身糖代谢异常,细胞分裂增殖功能亢进,卵巢对促性腺激素反应性增高,卵巢功能放大,可能是PCOS发病的关键因素。

英文摘要:

Objective To search for the role of impaired insulin signaling in the ovary reproductive failure and abnormal metabolic profiles in the AKT2 - mouse. Methods Adult, female129/C57BIJ6 (AKT2 - ) mice were used in these studies. Littermate wide types C57BL/6J( AKT2 + ), as well as mutant genotypes (AKT2 - ). The ovaries were abtained from 6 AKT2 + type mice as wall as 6 mutant genotypes, which was used for insulin stimulated glucose uptake study. By ovary transplantation on the day of 12 weeks, three genotypic mice were constructed with body AKT2 + and ovary AKT2 + in Group A, body AKT2 + and ovary AKT2 - in Group B, body AKT2 - and ovary AKT2 + in Group C. The vaginal smear was done to evaluate the recovery and cyclicity of transplanted ovaries with mutant or intact AKT2. Before execution, every group was randomly separated into basal and stimulated groups in which the mice were injected recombination FSH (0. 75 IU/g) , and then AKT2,GSK3[5,ERK-1 ,CYP17 and CYP19 were determined by RT-PCR in the ovaries, and the serum were reserved for the assay of HDL-C, CHO, TG, 17-OHP progesterone, E2, T, and LH. The weight of each mouse, their ovary and their fat pads and the estrus cycle,were also recorded. Results ( 1 ) The weight of fat pads beside ovaries and fold inguen in C group were significant higher than the other groups. (2) The level of 17-OHP progesterone in B group was higher than A or C group both in basal and FSH-stimulated groups. ( 3 ) In the basal group the expression of ERK- land CYP17 were enhanced. Moreover in FSH-dtimulated group, the expression of ERK-1 , CYP17, CYP19 and GSK3B in B group were higher as compared with the other groups. Conclusion ( 1 ) IR existed in the ovary of AKT2 - type, and the mice with AKT2 - type ovary had delayed cycle, PCO and high level of 17- OHP, which were similar with PCOS. (2) Metabolic dysfunction in the AKT2 - mice has close relationship with whole body condition, but not defective insulin signal within ovaries. (3) Def

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期刊信息
  • 《中华医学杂志》
  • 北大核心期刊(2011版)
  • 主管单位:中国科学技术协会
  • 主办单位:中华医学会
  • 主编:
  • 地址:北京市东四西大街42号
  • 邮编:100710
  • 邮箱:nmjc@cma.org.cn
  • 电话:010-85158355 85158180
  • 国际标准刊号:ISSN:0376-2491
  • 国内统一刊号:ISSN:11-2137/R
  • 邮发代号:2-588
  • 获奖情况:
  • 1992年与1996年连续两次在中宣部、国家科委、新闻...,1999年、2003年分别荣获首届国家期刊奖和第二届国...,中国期刊方阵“双高”期刊
  • 国内外数据库收录:
  • 美国化学文摘(网络版),荷兰文摘与引文数据库,荷兰医学文摘,美国生物医学检索系统,日本日本科学技术振兴机构数据库,中国中国科技核心期刊,中国北大核心期刊(2004版),中国北大核心期刊(2008版),中国北大核心期刊(2011版),中国北大核心期刊(2014版),中国北大核心期刊(2000版)
  • 被引量:101941