The First Clinical Medical College of Lanzhou University, The First Hospital of Lanzhou University, Lanzhou, China.
School of Basic Medical Sciences, Lanzhou University, Lanzhou, China.
Peptides. 2021 Nov;145:170624. doi: 10.1016/j.peptides.2021.170624. Epub 2021 Aug 8.
The purpose of this study was to explore the effect of dulaglutide on DHEA induced PCOS rats and its mechanism, to provide new drugs and research directions for clinical treatment of PCOS.
In this study, the PCOS model was established by giving female SD rats subcutaneous injection of DHEA for 21 consecutive days. After modeling, the treatment group was injected subcutaneously with three doses of dulaglutide for 3 weeks. The model group was injected with sterile ultrapure water, and the normal group did not get any intervention. The body weight changes of rats in each group were recorded from the first day when rats received the administration of dulaglutide. Three weeks later, the rats were fasted the night after the last treatment, determined fasting insulin and fasting glucose the next day. After the rats were anesthetized by chloral hydrate, more blood was collected from the heart of the rat. The serum insulin, testosterone and sex hormone binding globulin (SHBG) levels were detected by the enzyme-linked immunoassay method. After removing the adipose tissue, the obtained rat ovary tissue was used for subsequent experimental detection, using HE staining for morphology and follicular development analysis; qRT-PCR for the detection of 3βHSD, CYP17α1, CYP19α1, and StAR gene expression in ovarian tissue; and western blotting analysis of CYP17α1, CYP19α1, StAR protein expression and insulin level to verify whether dulaglutide has a therapeutic effect on PCOS in rats.
After treated with different concentrations of dulaglutide, we found that the body weight of rats in the treatment groups were reduced. Compared with the rats in PCOS group, the serum androgen level of rats in the treatment groups was significantly decreased, and the serum sex hormone binding protein content was significantly increased, and there was statistically significant difference between these groups and PCOS group. In terms of protein expression and gene regulation, the expression of 3βHSD, CYP19α1 and StAR in the ovarian tissue of rats in treatment groups were decreased significantly after received the treatment of dulaglutide, and there was statistically significant difference between these groups and PCOS group. In addition, dulaglutide reduced the insulin content in the ovarian tissue of PCOS rats.
Dulaglutide may reduce the hyperandrogenemia of PCOS rats by regulating the content of serum SHBG and the expression of 3βHSD, CYP19α1, and StAR related genes and proteins, thereby inhibiting the excessive development of small follicles and the formation of cystic follicles in the ovaries of PCOS rats, thereby improving polycystic ovary in PCOS rats. In addition, dulaglutide may reduce the weight of PCOS rats, further reducing the level of high androgen in PCOS rats, and improving the morphology of their polycystic ovaries.
本研究旨在探讨度拉糖肽对脱氢表雄酮诱导的多囊卵巢综合征（PCOS）大鼠的作用及其机制，为临床治疗 PCOS 提供新的药物和研究方向。
本研究通过给予雌性 SD 大鼠皮下注射脱氢表雄酮连续 21 天建立 PCOS 模型。造模后，治疗组皮下注射三剂量度拉糖肽治疗 3 周。模型组注射无菌超纯水，正常组不进行任何干预。记录各组大鼠从接受度拉糖肽给药的第一天开始的体重变化。3 周后，大鼠在最后一次治疗后的当晚禁食过夜，次日测定空腹胰岛素和空腹血糖。大鼠用氯醛水麻醉后，从心脏采集更多血液。采用酶联免疫吸附法检测血清胰岛素、睾酮和性激素结合球蛋白（SHBG）水平。去除脂肪组织后，对获得的大鼠卵巢组织进行后续实验检测，采用 HE 染色进行形态和卵泡发育分析；qRT-PCR 检测卵巢组织中 3βHSD、CYP17α1、CYP19α1 和 StAR 基因表达；Western blot 分析 CYP17α1、CYP19α1、StAR 蛋白表达和胰岛素水平，以验证度拉糖肽对大鼠 PCOS 是否具有治疗作用。
用不同浓度的度拉糖肽处理后，我们发现治疗组大鼠的体重减轻。与 PCOS 组大鼠相比，治疗组大鼠的血清雄激素水平明显降低，血清性激素结合蛋白含量明显升高，与 PCOS 组比较差异有统计学意义。在蛋白表达和基因调控方面，用度拉糖肽治疗后，治疗组大鼠卵巢组织中 3βHSD、CYP19α1 和 StAR 的表达明显下降，与 PCOS 组比较差异有统计学意义。此外，度拉糖肽降低了 PCOS 大鼠卵巢组织中的胰岛素含量。
度拉糖肽可能通过调节血清 SHBG 含量和 3βHSD、CYP19α1、StAR 相关基因和蛋白的表达来降低 PCOS 大鼠的高雄激素血症，从而抑制 PCOS 大鼠卵巢中小卵泡的过度发育和囊性卵泡的形成，从而改善 PCOS 大鼠的多囊卵巢。此外，度拉糖肽可能降低 PCOS 大鼠的体重，进一步降低 PCOS 大鼠的高雄激素水平，改善其多囊卵巢的形态。
