桃核承气汤对多囊卵巢综合征大鼠卵巢组织PI3K/AKT/mTOR信号通路的影响

doi:10.11958/20221420

天津医药 ›› 2023, Vol. 51 ›› Issue (6): 596-600.doi: 10.11958/20221420

桃核承气汤对多囊卵巢综合征大鼠卵巢组织PI3K/AKT/mTOR信号通路的影响

王毅¹(), 王海娇¹, 祁麟¹, 崔玉娇¹, 陈晓², 王岩³, 何红美¹^,^△

1 石家庄市第四医院检验科（邮编050011）
2 石家庄市第四医院产科（邮编050011）
3 石家庄市第四医院妇科（邮编050011）

收稿日期:2022-09-14 修回日期:2023-01-04 出版日期:2023-06-15 发布日期:2023-06-20
通讯作者: ^△E-mail：137099614@qq.com
作者简介:王毅（1982），女，主管检验师，主要从事妇科疾病方面研究。E-mail：wangyiyi632@163.com
基金资助:
河北省医学科学研究课题计划项目(20201381)

Effects of Taohe Chengqi Decoction on PI3K/AKT/mTOR signaling pathway in ovary tissue of rats with polycystic ovary syndrome

WANG Yi¹(), WANG Haijiao¹, QI Lin¹, CUI Yujiao¹, CHEN Xiao², WANG Yan³, HE Hongmei¹^,^△

1 Department of Laboratory Medicine, Shijiazhuang Fourth Hospital, Shijiazhuang 050011, China
2 Department of Obstetrics, Shijiazhuang Fourth Hospital, Shijiazhuang 050011, China
3 Department of Gynecology, Shijiazhuang Fourth Hospital, Shijiazhuang 050011, China

Received:2022-09-14 Revised:2023-01-04 Published:2023-06-15 Online:2023-06-20
Contact: ^△E-mail：137099614@qq.com

王毅, 王海娇, 祁麟, 崔玉娇, 陈晓, 王岩, 何红美. 桃核承气汤对多囊卵巢综合征大鼠卵巢组织PI3K/AKT/mTOR信号通路的影响[J]. 天津医药, 2023, 51(6): 596-600.

WANG Yi, WANG Haijiao, QI Lin, CUI Yujiao, CHEN Xiao, WANG Yan, HE Hongmei. Effects of Taohe Chengqi Decoction on PI3K/AKT/mTOR signaling pathway in ovary tissue of rats with polycystic ovary syndrome[J]. Tianjin Medical Journal, 2023, 51(6): 596-600.

摘要/Abstract

摘要：

目的探究桃核承气汤对多囊卵巢综合征（PCOS）大鼠卵巢组织磷脂酰肌醇3-激酶（PI3K）/丝氨酸/苏氨酸蛋白激酶B（AKT）/哺乳动物雷帕霉素靶蛋白（mTOR）信号通路的影响。方法将96只雌性SD大鼠随机分为对照组，PCOS组，二甲双胍组，桃核承气汤低、中、高剂量组，每组16只；除对照组外，其余各组大鼠皮下注射脱氢表雄酮构建PCOS模型。造模成功后二甲双胍组大鼠给予0.1 g/kg二甲双胍灌胃，桃核承气汤低、中、高剂量组分别给予1.89、3.78、7.56 g/kg桃核承气汤灌胃，对照组和PCOS组灌胃等量生理盐水，1次/d，共28 d。血糖仪检测空腹血糖（FPG）水平，酶联免疫吸附试验检测血清卵泡刺激素（FSH）、黄体生成素（LH）、雌二醇（E₂）、睾酮（T）、空腹胰岛素（FINS）水平，计算胰岛素抵抗指数（HOMA-IR）；苏木素伊红染色观察大鼠卵巢组织病理学情况；荧光定量PCR和蛋白免疫印迹实验分别检测大鼠卵巢组织PI3K/AKT/mTOR通路相关分子mRNA和蛋白表达。结果与对照组相比，PCOS组大鼠卵泡体积增大，含卵泡液，且细胞间隙增大、黄体减少、泡膜细胞层增生，血清FSH、E₂，卵巢组织中PI3K/AKT/mTOR通路mRNA和蛋白表达降低，LH、T、FPG、FINS及HOMA-IR水平升高（P<0.05）；与PCOS组相比，二甲双胍组及桃核承气汤低、中、高剂量组大鼠卵泡体积减小、黄体数目增加、泡膜细胞层增生现象减轻，血清FSH、E₂，卵巢组织中PI3K/AKT/mTOR通路mRNA和蛋白表达升高，LH、T、FPG、FINS及HOMA-IR水平降低（P<0.05）；桃核承气汤低、中、高剂量组上述指标变化呈剂量依赖性，低、中剂量组与二甲双胍组差异有统计学意义，高剂量组与二甲双胍组差异无统计学意义。结论桃核承气汤可促进PCOS模型大鼠性激素恢复正常水平，抑制胰岛素抵抗，这可能与其促进PI3K/AKT/mTOR信号通路激活有关。

关键词: 桃核承气汤, 多囊卵巢综合征, 磷脂酰肌醇3-激酶, 丝氨酸/苏氨酸蛋白激酶B, 哺乳动物雷帕霉素靶蛋白

Abstract:

Objective To explore the effect of Taohe Chengqi Decoction on phosphatidylinositol 3-kinase (PI3K)/serine/threonine protein kinase B (AKT)/mammalian target of rapamycin (mTOR) signaling pathway in ovarian tissue of a rat model of polycystic ovary syndrome (PCOS). Methods Ninety-six female SD rats were randomly divided into the control group, the PCOS group, the metformin group, the Taohe Chengqi Decoction low, medium and high dose groups, with 16 rats in each group. Except for the control group, the PCOS model was constructed by subcutaneous injection of dehydroepiandrosterone in the other groups. After successful model building, the metformin group was given 0.1 g/kg metformin by gavage, and the Taohe Chengqi Decoction low, medium and high dose groups were given 1.89 g/kg, 3.78 g/kg and 7.56 g/kg Taohe Chengqi Decoction by gavage, respectively. The control group and the PCOS group were given the same amount of normal saline by gavage, 1 time/d for 28 days. The fasting blood glucose (FPG) level was measured by blood glucose meter. Enzyme linked immunosorbent assay was used to detect serum levels of follicle stimulating hormone (FSH), luteinizing hormone (LH), estradiol (E₂), testosterone (T) and fasting insulin (FINS). Insulin resistance index (HOMA-IR) was calculated. Hematoxylin eosin staining was used to observe the histopathology of rat ovary. The mRNA and protein expression of PI3K/AKT/mTOR pathway in rat ovarian tissue were detected by fluorescence quantitative PCR and Western blot assay. Results Compared with the control group, the volume of follicles increased, contained follicular fluid, and the cell space increased, corpus luteum decreased, and the cell layer of theca proliferated, serum FSH, E₂, mRNA and protein expression of PI3K/AKT/mTOR pathway in ovarian tissue were decreased, and levels of LH, T, FPG, FINS and HOMA-IR were increased in the PCOS group (P<0.05). In the metformin group and the Taohe Chengqi Decoction low-dose, medium-dose and high-dose groups, the volume of follicles decreased, the number of corpus luteum increased, and the proliferation of alveolar cell layer decreased. Serum levels of FSH, E₂, mRNA and protein expression of PI3K/AKT/mTOR pathway in ovarian tissue were increased, and levels of LH, T, FPG, FINS and HOMA-IR were decreased (P<0.05). Changes of above indexes were dose-dependent in the low, medium and high dose groups of Taohe Chengqi Decoction. There were significant differences in changes of above indexes between the Taohe Chengqi Decoction low, medium-dose groups and the metformin group. There was no significant difference between the high-dose of Taohe Chengqi Decoction group and the metformin group. Conclusion Taohe Chengqi Decoction can restore normal levels of sex hormones and inhibit insulin resistance in PCOS model rats, which may be related to its promotion of PI3K/AKT/mTOR signal pathway activation.

Key words: Taohe Chengqi Decoction, polycystic ovary syndrome, phosphatidylinositol 3-kinase, serine/threonine protein kinase B, mammalian target of rapamycin

中图分类号:

R285.5

图/表 7

参考文献 21

[1]	JANNATIFAR R, PIROOZMANESH H, SAHRAEI S S, et al. Combination of alpha lipoic acid and metformin supplement improve assisted reproductive technologies outcomes in polycystic ovary syndrome patients[J]. Anat Cell Biol, 2022, 55(2):239-246. doi:10.5115/acb.21.242.
[2]	ZHANG J Q, XING C, HE B. Short period-administration of myo-inositol and metformin on hormonal and glycolipid profiles in patients with polycystic ovary syndrome:a systematic review and updated meta-analysis of randomized controlled trials[J]. Eur Rev Med Pharmacol Sci, 2022, 26(6):1792-1802. doi:10.26355/eurrev_202203_28322.
[3]	ROSENFIELD R L. Current concepts of polycystic ovary syndrome pathogenesis[J]. Curr Opin Pediatr, 2020, 32(5):698-706. doi:10.1097/MOP.0000000000000945.
[4]	LIU M, ZHU H, ZHU Y, et al. Guizhi Fuling Wan reduces autophagy of granulosa cell in rats with polycystic ovary syndrome via restoring the PI3K/AKT/mTOR signaling pathway[J]. J Ethnopharmacol, 2021, 270(1):113821-113831. doi:10.1016/j.jep.2021.113821.
[5]	杨伟娜, 杨军娜, 姚伊. 桃核承气汤通过JAK2/STAT1信号通路干预急性盆腔炎模型大鼠的研究[J]. 中国医院用药评价与分析, 2019, 19(9):1075-1078,1082.
	YANG W N, YANG J N, YAO Y. Research of the intervention of Taohechengqi Decoction on model rats with acute pelvic inflammatory disease through JAK2/STAT1 signal pathway[J]. Evaluation and Analysis of Drug-Use in Hospitals of China, 2019, 19(9):1075-1078,1082. doi:10.14009/j.issn.1672-2124.2019.09.010.
[6]	张成玲, 谭艺, 魏庆骅, 等. 基于网络药理学的桃核承气汤治疗子宫内膜异位症的作用机制研究[J]. 世界中医药, 2021, 16(23):3472-3477.
	ZHANG C L, TAN Y, WEI Q H, et al. Deciphering mechanisms of Taohe Chengqi Decoction in the treatment of endometriosis based on network pharmacology[J]. World Chinese Medicine, 2021, 16(23):3472-3477. doi:10.3969/j.issn.1673-7202.2021.23.012.
[7]	田立霞, 姜丹, 杨瑾, 等. 促排汤对多囊卵巢综合征大鼠胰岛素抵抗的影响[J]. 中成药, 2021, 43(6):1627-1631.
	TIAN L X, JIANG D, YANG J, et al. Effect of cupai decoction on insulin resistance in rats with polycystic ovary syndrome[J]. Chinese Traditional Patent Medicine, 2021, 43(6):1627-1631. doi:10.3969/j.issn.1001-1528.2021.06.046.
[8]	张明昊, 高一盈, 赵盈盈, 等. 桃核承气汤对肾纤维化大鼠的保护作用机制研究[J]. 中国临床药理学杂志, 2021, 37(17):2324-2327,2334.
	ZHANG M H, GAO Y Y, ZHAO Y Y, et al. Protective effect and mechanism of Taohe Chengqi Decoction on renal fibrosis model in rats[J]. The Chinese Journal of Clinical Pharmacology, 2021, 37(17):2324-2327,2334. doi:10.13699/j.cnki.1001-6821.2021.17.019.
[9]	FALCETTA P, BENELLI E, MOLINARO A, et al. Effect of aging on clinical features and metabolic complications of women with polycystic ovary syndrome[J]. J Endocrinol Invest, 2021, 44(12):2725-2733. doi:10.1007/s40618-021-01594-5.
[10]	KRENTOWSKA A, ŁEBKOWSKA A, JACEWICZ-ŚWIĘCKA M, et al. Metabolic syndrome and the risk of cardiovascular complications in young patients with different phenotypes of polycystic ovary syndrome[J]. Endocrine, 2021, 72(2):400-410. doi:10.1007/s12020-020-02596-8.
[11]	ALBAGHDADI A J H, KAN F W K. Therapeutic potentials of low-dose tacrolimus for aberrant endometrial features in polycystic ovary syndrome[J]. Int J Mol Sci, 2021, 22(6):2872. doi:10.3390/ijms22062872.
[12]	QI X, YUN C, LIAO B, et al. The therapeutic effect of interleukin-22 in high androgen-induced polycystic ovary syndrome[J]. J Endocrinol, 2020, 245(2):281-289. doi:10.1530/JOE-19-0589.
[13]	沈文娟, 尤天娇, 金宝, 等. 多囊卵巢综合征中西医病因病机及治疗研究进展[J]. 辽宁中医杂志, 2021, 48(12):196-199.
	SHEN W J, YOU T J, JIN B, et al. Advances in etiology pathogenesis and treatment of polycystic ovary syndrome[J]. Liaoning Journal of Traditional Chinese Medicine, 2021, 48(12):196-199. doi:10.13192/j.issn.1000-1719.2021.12.055.
[14]	郑玮琳, 刘奇, 梁雪芳, 等. 经方治疗妇人慢性盆腔痛探讨[J]. 中华中医药杂志, 2019, 34(4):1632-1634.
	ZHENG W L, LIU Q, LIANG X F, et al. Discussion on the chronic pelvic pain treatment by classical prescription[J]. China Journal of Traditional Chinese Medicine and Pharmacy, 2019, 34(4):1632-1634.
[15]	郑秋霞, 应翩, 张洁, 等. 桃核承气汤加减治疗血瘀型子宫内膜异位症的疗效及对患者肿瘤标志物水平的影响[J]. 中国妇幼保健, 2021, 36(6):1257-1259.
	ZHENG Q X, YING P, ZHANG J, et al. The effect of Taohe Chengqi Decoction on blood stasis endometriosis and the level of tumor markers[J]. Maternal and Child Health Care of China, 2021, 36(6):1257-1259. doi:10.19829/j.zgfybj.issn.1001-4411.2021.06.014.
[16]	许金榜, 林莺. 六经辨证治疗多囊卵巢综合征探究[J]. 中国中医基础医学杂志, 2016, 22(9):1178-1180.
	XU J B, LIN Y, et al. Discussion of the treatment of polycystic ovary syndrome by the six meridian syndrome differentiation[J]. Chinese Journal of Basic Medicine in Traditional Chinese Medicine, 2016, 22(9):1178-1180. doi:10.19945/j.cnki.issn.1006-3250.2016.09.015.
[17]	VATIER C, CHRISTIN-MAITRE S, VIGOUROUX C. Role of insulin resistance on fertility - Focus on polycystic ovary syndrome[J]. Ann Endocrinol (Paris), 2022, 83(3):199-202. doi:10.1016/j.ando.2022.04.004.
[18]	ZHOU Z, TU Z, ZHANG J, et al. Follicular fluid-derived exosomal MicroRNA-18b-5p regulates PTEN-mediated PI3K/Akt/mTOR signaling pathway to inhibit polycystic ovary syndrome development[J]. Mol Neurobiol, 2022, 59(4):2520-2531. doi:10.1007/s12035-021-02714-1.
[19]	XU B, DAI W, LIU L, et al. Metformin ameliorates polycystic ovary syndrome in a rat model by decreasing excessive autophagy in ovarian granulosa cells via the PI3K/AKT/mTOR pathway[J]. Endocr J, 2022, 69(7):863-875. doi:10.1507/endocrj.EJ21-0480.
[20]	GUO R, ZHENG H, LI Q, et al. Melatonin alleviates insulin resistance through the PI3K/AKT signaling pathway in ovary granulosa cells of polycystic ovary syndrome[J]. Reprod Biol, 2022, 22(1):100594. doi:10.1016/j.repbio.2021.100594.
[21]	ABUELEZZ N Z, SHABANA M E, ABDEL-MAGEED H M, et al. Nanocurcumin alleviates insulin resistance and pancreatic deficits in polycystic ovary syndrome rats:Insights on PI3K/AKT/mTOR and TNF-α modulations[J]. Life Sci, 2020, 256(1):118003-118013. doi:10.1016/j.lfs.2020.118003.

基因名称	引物序列（5′→3′）	产物大小（bp）
PI3K	上游：GCCTGCTCTGTAGTGGTAGATG	326
	下游：GGAGGTGTGTTGGTAATGTAGC	326
AKT	上游：CTGAGATGATGGAGGTAGCG	264
	下游：CCGAGGAGTTTGAGATAATCG	264
mTOR	上游：GCTTATCAAGCAAGCGACATCTCA	206
	下游：TCCACTGGAAGCACAGACCAAG	206
GAPDH	上游：ATCCGTTGTGGATCTGACATG	311
	下游：CAAAGGTGGAAGAATGGGAGT	311

基因名称	引物序列（5′→3′）	产物大小（bp）
PI3K	上游：GCCTGCTCTGTAGTGGTAGATG	326
	下游：GGAGGTGTGTTGGTAATGTAGC	326
AKT	上游：CTGAGATGATGGAGGTAGCG	264
	下游：CCGAGGAGTTTGAGATAATCG	264
mTOR	上游：GCTTATCAAGCAAGCGACATCTCA	206
	下游：TCCACTGGAAGCACAGACCAAG	206
GAPDH	上游：ATCCGTTGTGGATCTGACATG	311
	下游：CAAAGGTGGAAGAATGGGAGT	311

组别	FSH（IU/L）	LH（IU/L）	E₂（pmol/L）	T（ng/L）
对照组	3.50±0.68	11.08±1.14	24.14±3.25	17.92±3.38
PCOS组	1.03±0.34^a	18.91±1.42^a	6.03±0.98^a	86.36±6.20^a
二甲双胍组	3.41±0.45^b	11.39±1.40^b	22.94±2.36^b	18.76±5.33^b
低剂量组	1.76±0.38^bc	16.24±1.03^bc	10.20±1.35^bc	60.52±5.79^bc
中剂量组	2.56±0.40^bcd	14.03±1.26^bcd	16.03±1.52^bcd	41.75±4.20^bcd
高剂量组	3.39±0.41^bde	11.20±1.04^bde	21.09±2.06^bde	20.01±4.92^bde
F	80.629^＊＊	111.039^＊＊	204.619^＊＊	488.227^＊＊

组别	FSH（IU/L）	LH（IU/L）	E₂（pmol/L）	T（ng/L）
对照组	3.50±0.68	11.08±1.14	24.14±3.25	17.92±3.38
PCOS组	1.03±0.34^a	18.91±1.42^a	6.03±0.98^a	86.36±6.20^a
二甲双胍组	3.41±0.45^b	11.39±1.40^b	22.94±2.36^b	18.76±5.33^b
低剂量组	1.76±0.38^bc	16.24±1.03^bc	10.20±1.35^bc	60.52±5.79^bc
中剂量组	2.56±0.40^bcd	14.03±1.26^bcd	16.03±1.52^bcd	41.75±4.20^bcd
高剂量组	3.39±0.41^bde	11.20±1.04^bde	21.09±2.06^bde	20.01±4.92^bde
F	80.629^＊＊	111.039^＊＊	204.619^＊＊	488.227^＊＊

组别	FPG（mmoL/L）	FINS（mIU/L）	HOMA-IR
对照组	5.59±0.38	64.17±5.10	15.94±2.21
PCOS组	7.80±0.33^a	124.23±7.86^a	43.07±3.28^a
二甲双胍组	5.66±0.35^b	68.30±6.24^b	17.18±2.52^b
低剂量组	7.01±0.30^bc	101.25±5.33^bc	31.55±3.76^bc
中剂量组	6.42±0.41^bcd	85.00±6.27^bcd	24.25±2.02^bcd
高剂量组	5.69±0.40^bde	70.02±7.30^bde	17.71±3.43^bde
F	97.499^＊＊	212.257^＊＊	209.213^＊＊

桃核承气汤对多囊卵巢综合征大鼠卵巢组织PI3K/AKT/mTOR信号通路的影响

Effects of Taohe Chengqi Decoction on PI3K/AKT/mTOR signaling pathway in ovary tissue of rats with polycystic ovary syndrome

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组别	PI3K mRNA	AKT mRNA	mTOR mRNA
对照组	1.00±0.08	1.01±0.05	0.99±0.09
PCOS组	0.32±0.04^a	0.28±0.03^a	0.16±0.02^a
二甲双胍组	1.01±0.07^b	1.00±0.10^b	0.98±0.12^b
低剂量组	0.51±0.06^bc	0.47±0.06^bc	0.40±0.06^bc
中剂量组	0.78±0.08^bcd	0.72±0.07^bcd	0.65±0.08^bcd
高剂量组	0.98±0.10^bde	0.97±0.11^bde	0.96±0.09^bde
F	123.934^＊＊	135.045^＊＊	143.672^＊＊

组别	p-PI3K/PI3K	p-AKT/AKT	mTOR/GAPDH
对照组	1.69±0.23	1.51±0.26	1.39±0.20
PCOS组	0.56±0.06^a	0.43±0.07^a	0.32±0.04^a
二甲双胍组	1.61±0.27^b	1.49±0.27^b	1.36±0.19^b
低剂量组	0.90±0.09^bc	0.78±0.07^bc	0.66±0.06^bc
中剂量组	1.28±0.18^bcd	1.12±0.15^bcd	0.98±0.10^bcd
高剂量组	1.58±0.20^bde	1.47±0.21^bde	1.34±0.19^bde
F	47.072^＊＊	44.354^＊＊	73.491^＊＊

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