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针刺通过激活多囊卵巢综合征大鼠模型中的PI3K/AKT通路改善子宫内膜血管生成。

Acupuncture Improves Endometrial Angiogenesis by Activating PI3K/AKT Pathway in a Rat Model with PCOS.

作者信息

Xing Liwei, Chen Yang, He Zhe, He Ming, Sun Yuhuan, Xu Jinlong, Wang Jian, Zhuang Haina, Ren Zeqin, Chen Ying, Yang Jun, Cheng Shuluo, Zhao Rong

机构信息

Yunnan University of Chinese Medicine, Kunming, China.

Hainan Women and Children's Medical Center (Women and Children's Health Care Center of Hainan Province, Hainan Children's Hospital, Children's Hospital of Fudan University at Hainan, Hainan Obstetrics and Gynecology Hospital), Haikou, China.

出版信息

Evid Based Complement Alternat Med. 2022 Aug 24;2022:1790041. doi: 10.1155/2022/1790041. eCollection 2022.

Abstract

BACKGROUND

Acupuncture, a treatment derived from traditional Chinese medicine, can effectively relieve the symptoms and improve pregnancy outcome in patients with polycystic ovary syndrome (PCOS); however, its mechanism remains unclear. This study aimed at investigating whether acupuncture could improve endometrial angiogenesis and thus endometrial receptivity via activating PI3K/AKT pathway in PCOS rats.

METHODS

We established a rat model with PCOS, which was induced by DHEA. Acupuncture was performed every other day for 15 days, and the PI3K inhibitor (LY294002) was intraperitoneal injected 30 mins before acupuncture treatment. Females rats were mated with male SPF SD rats in a ratio of 2 : 1 after treatment and sacrificed on the 5th day when the vaginal plug was identified. The number of implantation sites was observed, followed by ovarian and endometrial morphology detected with hematoxylin-eosin staining and a scanning electron microscope, estrous cycle detected with vaginal smear analysis, and sex hormones and angiogenesis-related PI3K/AKT gene/protein expression detected with enzyme-linked immunosorbent assay, western blotting, immune histochemistry, and quantitative real-time PCR.

RESULTS

Acupuncture notably improved implantation sites' number, endometrial receptivity factors including endometrial morphology, pinopodes, HOX-10, and LIF protein expression, as well as angiogenesis and PI3K/AKT pathway factors such as VEGF, VEGFR2, Ang-1, PI3K, AKT, and P-AKT gene/protein expression and the level of eNOS and NO in the endometrium of rats with PCOS; PCOS-like symptoms were alleviated as well. The efficacy of acupuncture on a rat model with PCOS was counteracted by the combination with the PI3K inhibitor.

CONCLUSION

Acupuncture improves endometrial angiogenesis by activating the PI3K/AKT pathway, thus promoting endometrial receptivity and the number of implantation sites in rats with PCOS.

摘要

背景

针灸是一种源自传统中医的治疗方法,能有效缓解多囊卵巢综合征(PCOS)患者的症状并改善妊娠结局;然而,其机制尚不清楚。本研究旨在探讨针灸是否能通过激活PCOS大鼠的PI3K/AKT通路来改善子宫内膜血管生成,进而改善子宫内膜容受性。

方法

我们建立了由脱氢表雄酮(DHEA)诱导的PCOS大鼠模型。每隔一天进行一次针灸,共15天,在针灸治疗前30分钟腹腔注射PI3K抑制剂(LY294002)。治疗后,雌性大鼠以2∶1的比例与雄性SPF SD大鼠交配,在确认有阴道栓后的第5天处死。观察着床点数量,随后用苏木精-伊红染色和扫描电子显微镜检测卵巢和子宫内膜形态,用阴道涂片分析检测发情周期,并用酶联免疫吸附测定、蛋白质印迹法、免疫组织化学和定量实时聚合酶链反应检测性激素和血管生成相关的PI3K/AKT基因/蛋白表达。

结果

针灸显著增加了着床点数量,改善了子宫内膜容受性相关因素,包括子宫内膜形态、微绒毛、HOX-10和白血病抑制因子(LIF)蛋白表达,以及血管生成和PI3K/AKT通路相关因素,如血管内皮生长因子(VEGF)、血管内皮生长因子受体2(VEGFR2)、血管生成素-1(Ang-1)、PI3K、AKT和磷酸化AKT(P-AKT)基因/蛋白表达以及PCOS大鼠子宫内膜中内皮型一氧化氮合酶(eNOS)和一氧化氮(NO)水平;PCOS样症状也得到缓解。PI3K抑制剂与针灸联合使用可抵消针灸对PCOS大鼠模型的疗效。

结论

针灸通过激活PI3K/AKT通路改善子宫内膜血管生成,从而促进PCOS大鼠的子宫内膜容受性和着床点数量。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f9ae/9433287/93ff634eda2b/ECAM2022-1790041.001.jpg

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