基于PI3K/Akt通路探讨穴位埋线改善PCOS-IR患者IVF卵细胞质量
|
摘要
目的:观察穴位埋线法干预调节PI3K/Akt信号通路关键效应分子Akt、与通路相关的GLUT4水平及其对胰岛素抵抗多囊卵巢综合征(PCOS)患者体外受精(IVF)卵细胞质量的影响。方法:选取行体外受精-胚胎移植(IVF-ET)的胰岛素抵抗PCOS患者60例,按照随机数字表法分为穴位埋线治疗组(穴位埋线+GnRH-a+达英-35双降治疗),基础治疗组(GnRH-a+达英-35双降治疗),每组各30例,穴位埋线治疗组于GnRH-a降调节周期的第10天,降调节日,COH周期经净第1天埋线治疗。观察穴位埋线治疗组患者治疗前后胰岛素抵抗指标HOMA-IR变化,两组患者的受精率、优胚率、临床妊娠率、胚胎发育时间参数(t2、t3、t4、t5、s2、cc2),以及PI3K/Akt信号转导通路p-Akt、GLUT4蛋白水平。结果:①穴位埋线治疗组取卵日HOMA-IR显著低于治疗前(P<0.05);②与基础治疗组比较,穴位埋线治疗组受精率、临床妊娠率差异无统计学意义,但有升高的趋势,优胚率显著增高(P<0.05);t2、t3、t5、s2时间段比较,两组差异无统计学意义,在t4、cc2时间段的比较中,穴位埋线治疗组发育时间显著快于基础治疗组(P<0.05);③穴位埋线治疗组较基础治疗组p-Akt和GLUT4蛋白表达显著上调(P<0.05)。结论:穴位埋线可能是通过PI3K/Akt信号转导通路,上调GLUT4蛋白表达,改善胰岛素抵抗状态,从而提高PCOS患者IVF卵细胞质量。
Objective: To observe the effects of acupoint embedding method on the regulation of the key effector molecule Akt of PI3 K/Akt signaling pathway and the level of GLUT4 associated with pathway on the quality of IVF egg cells in patients with insulin resistance PCOS. Methods: Sixty patients with insulin resistance PCOS, who underwent in vitro fertilizationembryo transfer(IVF-ET) were randomly divided into acupoint embedding treatment group(acupoint embedding combined with GnRH-a+Daying-35 double descending treatment) and basic treatment group(GnRH-a+Daying-35 double-dose treatment), 30 cases in each group. The acupoint catgutization treatment group(GnRH-a) decreased the regulation of the 10 th day of the previous cycle. On the day of the down regulation, the first day of menstruation of the COH cycle. The changes of insulin resistance index,HOMA-IR, before and after treatment in the acupoint embedding treatment group were observed. The fertilization rate, the rate of excellent embryos, the clinical pregnancy rate, the time parameters, and the levels of p-Akt and GLUT4 proteins in the PI3 K/Akt signal pathway were observed. Results: ①With the treatment of the acupoint embedding, HOMA-IR was significantly lower than that before treatment(P<0.05). ②Compared with the basic treatment group, the fertilization rate and clinical pregnancy rate of the acupoint embedding treatment group were not statistically significant, but there was a growth trend, the rate of excellent embryos was significantly increased(P<0.05); t2, t3, t5 and s2 time period comparison, the difference between the two groups was not statistically significant, in the t4, cc2 time period comparison, the development time of the acupoint embedding treatment group was significantly faster than that of the basic treatment group(P<0.05). ③The expressions of p-Akt and GLUT4 protein were upregulated in the acupoint embedding group compared with the basic treatment group(P<0.05). Conclusion: Acupoint embedding may be through PI3 K/Akt signal transduction pathway, up-regulate GLUT4 protein expression, improve insulin resistance, thereby improving IVF egg cell quality in PCOS patients, and ultimately improving the outcome of pregnancy.
Objective: To observe the effects of acupoint embedding method on the regulation of the key effector molecule Akt of PI3 K/Akt signaling pathway and the level of GLUT4 associated with pathway on the quality of IVF egg cells in patients with insulin resistance PCOS. Methods: Sixty patients with insulin resistance PCOS, who underwent in vitro fertilizationembryo transfer(IVF-ET) were randomly divided into acupoint embedding treatment group(acupoint embedding combined with GnRH-a+Daying-35 double descending treatment) and basic treatment group(GnRH-a+Daying-35 double-dose treatment), 30 cases in each group. The acupoint catgutization treatment group(GnRH-a) decreased the regulation of the 10 th day of the previous cycle. On the day of the down regulation, the first day of menstruation of the COH cycle. The changes of insulin resistance index,HOMA-IR, before and after treatment in the acupoint embedding treatment group were observed. The fertilization rate, the rate of excellent embryos, the clinical pregnancy rate, the time parameters, and the levels of p-Akt and GLUT4 proteins in the PI3 K/Akt signal pathway were observed. Results: ①With the treatment of the acupoint embedding, HOMA-IR was significantly lower than that before treatment(P<0.05). ②Compared with the basic treatment group, the fertilization rate and clinical pregnancy rate of the acupoint embedding treatment group were not statistically significant, but there was a growth trend, the rate of excellent embryos was significantly increased(P<0.05); t2, t3, t5 and s2 time period comparison, the difference between the two groups was not statistically significant, in the t4, cc2 time period comparison, the development time of the acupoint embedding treatment group was significantly faster than that of the basic treatment group(P<0.05). ③The expressions of p-Akt and GLUT4 protein were upregulated in the acupoint embedding group compared with the basic treatment group(P<0.05). Conclusion: Acupoint embedding may be through PI3 K/Akt signal transduction pathway, up-regulate GLUT4 protein expression, improve insulin resistance, thereby improving IVF egg cell quality in PCOS patients, and ultimately improving the outcome of pregnancy.
引文
[1]Knochenhauer E S,Key T J,Kahsar-Miller M,et al.Prevalence of the polycystic ovary syndrome in unselected black and white women of the Southeastern United States:A prospective study.J Clin Endocrinol Metabol,1998,83(9):3078-3082
[2]Martin D E,Hall M N.The expanding TOR signaling network.Curr Opin Cell Biol,2005,17:158-166
[3]Schmelzle T,Hall M N.TOR,a central controller of cell growth.Cell,2000,103:253-262
[4]Tsang C K,Qi H,Liu L F,et al.Targeting mammalian target of rapamycin(mTOR)for health and diseases.Drug Discov Today,2007,12:112-124
[5]周密,丁旭,宋晖,等.多囊卵巢综合征患者血清抗苗勒管激素与肥胖、胰岛素抵抗程度的相关性分析.现代生物医学进展,2018,18(10):1916-1921
[6]多囊卵巢综合征诊断中华人民共和国卫生行业标准.中华妇产科杂志,2012,47(1):74-75
[7]Hudson C C,Liu M,Chiang G G,et al.Regulation of hypoxia inducible factor lalpha expression and function by the mammalian target of rapamycin.Mol Cell Biol,2002,22(20):7004-7014
[8]李静,王长河,张秀峰.屈螺酮炔雌醇联合二甲双胍治疗PCOS合并胰岛素抵抗的子宫内膜癌前期及癌早期患者的临床研究.现代妇产科进展,2017,26(4):293-294
[9]洪艳丽,吴飞.补肾化痰方对多囊卵巢综合征胰岛素抵抗Akt通路调控的实验研究.中国中西医结合杂志,2014,34(2):230-234
[10]黄伟,王佳捷,陈霞,等.穴位埋线疗法对单纯性肥胖患者胰岛素抵抗的影响.中华中医药杂志,2017,32(8):3646-3649
[11]辛思源,杨志新,郭建恩,等.关于俞募配穴法干预方法的临床研究进展.中华中医药杂志,2017,32(2):690-692
[12]Chi M,Ye Y,Zhang X D,et al.Insulin induces drug resistance in melanoma through activation of the PI3K/Akt pathway.Drug Des Devel Ther,2014,2(8):255-262
[13]Zhang Y,Hai J,Cao M,et al.Silibinin ameliorates steatosis and insulin resistance during non-alcoholic fatty liver disease development partly through targeting IRS-1,PI3K/Akt pathway.Int Immunopharmacol,2013,17(3):714-720
[14]Ussar S,Vienberg S G,Kahn C R.Receptor antibodies as novel therapeutics for diabetes.Sci Transl Med,2011,3(113):113-147
[15]Galagovsky D,Katz M J,Acevedo J M,et al.The Drosophila insulindegradingenzyme restricts growth by modulating the PI3K pathway in a cell-autonomous manner.Mol Biol Cell,2014,25(6):916-924,1541-1544
[16]Zhang Y,Liu X,Han L,et al.Regulation of lipid and glucose homeostasis by mango tree leaf extract is mediated by AMPK and PI3K/Akt signaling pathways.Food Chem,2013,141(3):2896-2905
[2]Martin D E,Hall M N.The expanding TOR signaling network.Curr Opin Cell Biol,2005,17:158-166
[3]Schmelzle T,Hall M N.TOR,a central controller of cell growth.Cell,2000,103:253-262
[4]Tsang C K,Qi H,Liu L F,et al.Targeting mammalian target of rapamycin(mTOR)for health and diseases.Drug Discov Today,2007,12:112-124
[5]周密,丁旭,宋晖,等.多囊卵巢综合征患者血清抗苗勒管激素与肥胖、胰岛素抵抗程度的相关性分析.现代生物医学进展,2018,18(10):1916-1921
[6]多囊卵巢综合征诊断中华人民共和国卫生行业标准.中华妇产科杂志,2012,47(1):74-75
[7]Hudson C C,Liu M,Chiang G G,et al.Regulation of hypoxia inducible factor lalpha expression and function by the mammalian target of rapamycin.Mol Cell Biol,2002,22(20):7004-7014
[8]李静,王长河,张秀峰.屈螺酮炔雌醇联合二甲双胍治疗PCOS合并胰岛素抵抗的子宫内膜癌前期及癌早期患者的临床研究.现代妇产科进展,2017,26(4):293-294
[9]洪艳丽,吴飞.补肾化痰方对多囊卵巢综合征胰岛素抵抗Akt通路调控的实验研究.中国中西医结合杂志,2014,34(2):230-234
[10]黄伟,王佳捷,陈霞,等.穴位埋线疗法对单纯性肥胖患者胰岛素抵抗的影响.中华中医药杂志,2017,32(8):3646-3649
[11]辛思源,杨志新,郭建恩,等.关于俞募配穴法干预方法的临床研究进展.中华中医药杂志,2017,32(2):690-692
[12]Chi M,Ye Y,Zhang X D,et al.Insulin induces drug resistance in melanoma through activation of the PI3K/Akt pathway.Drug Des Devel Ther,2014,2(8):255-262
[13]Zhang Y,Hai J,Cao M,et al.Silibinin ameliorates steatosis and insulin resistance during non-alcoholic fatty liver disease development partly through targeting IRS-1,PI3K/Akt pathway.Int Immunopharmacol,2013,17(3):714-720
[14]Ussar S,Vienberg S G,Kahn C R.Receptor antibodies as novel therapeutics for diabetes.Sci Transl Med,2011,3(113):113-147
[15]Galagovsky D,Katz M J,Acevedo J M,et al.The Drosophila insulindegradingenzyme restricts growth by modulating the PI3K pathway in a cell-autonomous manner.Mol Biol Cell,2014,25(6):916-924,1541-1544
[16]Zhang Y,Liu X,Han L,et al.Regulation of lipid and glucose homeostasis by mango tree leaf extract is mediated by AMPK and PI3K/Akt signaling pathways.Food Chem,2013,141(3):2896-2905