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二十二碳六烯酸衍生物(-苄基二十二碳六烯酰胺)作为一种治疗卵巢损伤的潜在治疗候选物在小鼠模型中的研究。

A Docosahexaenoic Acid Derivative (-Benzyl Docosahexaenamide) as a Potential Therapeutic Candidate for Treatment of Ovarian Injury in the Mouse Model.

机构信息

Guangdong Provincial Key Laboratory of Pharmaceutical Bioactive Substances, School of Biosciences and Biopharmaceutics, Guangdong Pharmaceutical University, Guangzhou 510006, China.

School of Pharmacy, Guangdong Pharmaceutical University, Guangzhou 510006, China.

出版信息

Molecules. 2022 Apr 25;27(9):2754. doi: 10.3390/molecules27092754.

DOI:10.3390/molecules27092754
PMID:35566104
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9102315/
Abstract

Commonly used clinical chemotherapy drugs, such as cyclophosphamide (CTX), may cause injury to the ovaries. Hormone therapies can reduce the ovarian injury risk; however, they do not achieve the desired effect and have obvious side effects. Therefore, it is necessary to find a potential therapeutic candidate for ovarian injury after chemotherapy. -Benzyl docosahexaenamide (NB-DHA) is a docosahexaenoic acid derivative. It was recently identified as the specific macamide with a high degree of unsaturation in maca (). In this study, the purified NB-DHA was administered intragastrically to the mice with CTX-induced ovarian injury at three dose levels. Blood and tissue samples were collected to assess the regulation of NB-DHA on ovarian function. The results indicated that NB-DHA was effective in improving the disorder of estrous cycle, and the CTX+NB-H group can be recovered to normal levels. NB-DHA also significantly increased the number of primordial follicles, especially in the CTX+NB-M and CTX+NB-H groups. Follicle-stimulating hormone and luteinizing hormone levels in all treatment groups and estradiol levels in the CTX+NB-H group returned to normal. mRNA expression of ovarian development-related genes was positive regulated. The proportion of granulosa cell apoptosis decreased significantly, especially in the CTX+NB-H group. The expression of anti-Müllerian hormone and follicle-stimulating hormone receptor significantly increased in ovarian tissues after NB-DHA treatment. NB-DHA may be a promising agent for treating ovarian injury.

摘要

常用的临床化疗药物,如环磷酰胺(CTX),可能会对卵巢造成损伤。激素疗法可以降低卵巢损伤的风险;然而,它们并没有达到预期的效果,而且有明显的副作用。因此,有必要寻找一种潜在的治疗化疗后卵巢损伤的候选药物。-二十二碳六烯酸苄酯(NB-DHA)是二十二碳六烯酸的衍生物。它最近被确定为玛咖中高度不饱和的特定酰胺()。在这项研究中,将纯化的 NB-DHA 以三个剂量水平灌胃给 CTX 诱导的卵巢损伤小鼠。采集血液和组织样本,评估 NB-DHA 对卵巢功能的调节作用。结果表明,NB-DHA 能有效改善动情周期紊乱,CTX+NB-H 组可恢复正常水平。NB-DHA 还显著增加了原始卵泡的数量,特别是在 CTX+NB-M 和 CTX+NB-H 组中。所有治疗组的卵泡刺激素和黄体生成素水平以及 CTX+NB-H 组的雌二醇水平均恢复正常。卵巢发育相关基因的 mRNA 表达呈正调控。颗粒细胞凋亡的比例明显下降,尤其是在 CTX+NB-H 组。NB-DHA 处理后卵巢组织中抗苗勒管激素和卵泡刺激素受体的表达显著增加。NB-DHA 可能是治疗卵巢损伤的一种有前途的药物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/23a8/9102315/978c39f21419/molecules-27-02754-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/23a8/9102315/001f8bdf4be1/molecules-27-02754-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/23a8/9102315/83a4a3bc961b/molecules-27-02754-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/23a8/9102315/ab106068971e/molecules-27-02754-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/23a8/9102315/c246fb63cadf/molecules-27-02754-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/23a8/9102315/978c39f21419/molecules-27-02754-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/23a8/9102315/001f8bdf4be1/molecules-27-02754-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/23a8/9102315/83a4a3bc961b/molecules-27-02754-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/23a8/9102315/ab106068971e/molecules-27-02754-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/23a8/9102315/c246fb63cadf/molecules-27-02754-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/23a8/9102315/978c39f21419/molecules-27-02754-g005.jpg

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