Establishment and evaluation study of non-obese polycystic ovary syndrome rat model
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1.College of Life Science, Beijing University of Chinese Medicine;2.College of Traditional Chinese Medicine(TCM), Beijing University of Chinese Medicine;3.Beijing Research Institute of Chinese Medicine, Beijing University of Chinese Medicine;4.Key Laboratory of Famous Doctors and Famous Prescriptions of National Administration of TCM;5.College of Traditional Chinese Medicine (TCM), Beijing University of Chinese Medicine;6.College of Traditional Chinese Medicine, Beijing University of Chinese Medicine

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The National Natural Science Foundation of China (General Program, Key Program, Major Research Plan), Collaborative research project “Decoding Chinese Medicine” of Beijing University of Traditional Chinese Medicine, Development and training of a program for the treatment of polycystic ovary syndrome by combining traditional Chinese and Western medicine with cyclic therapy

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    Abstract:

    Objective To establish a stable rat model of non-obese polycystic ovary syndrome (PCOS) with clinical characteristics. Methods The dehydroepiandrosterone (DHEA) was used to establish a PCOS rats model by subcutaneous injection. 3-week-old SD rats were divided into a normal group, a 6 mg/kg DHEA model group, and a 60 mg/kg DHEA model group, and the model groups were subcutaneously injected with DHEA according to the corresponding dose daily, while the normal group was subcutaneously injected with glycerol daily for 21 consecutive days. The model was evaluated with ovarian histopathology as the gold standard to determine the optimal dosage of DHEA-induced PCOS rat model. On this basis, the optimal DHEA modeling dose was selected, and the stopping and continuing modeling groups were set up respectively, to observe the model for 28 days to investigate maintenance of model. The stopping modeling group was no longer given DHEA, and the continuing modeling group was subcutaneously injected with 60 mg/kg DHEA every 48 h. The evaluation indicators include body mass, estrous cycle, fasting blood glucose and serum insulin, histopathologic morphology of the ovaries and serum sex hormone levels. Results 1) Compared with the normal group, body mass in the 6 mg/kg DHEA model group and the 60 mg/kg DHEA model group showed no significant difference, and the estrous cycles were irregular in both groups. And there were more cystically dilated large follicles in theovaries, with fewer mature follicles, reduced layers of granulosa cells in a sparse and disorganized manner, and fewer luteum in the 6 mg/kg DHEA model group and the 60 mg/kg DHEA model group. Furthermore, serum T and E2 levels were significantly higher in the 60 mg/kg DHEA model group (P<0.05). 2) The stopping modeling group: the model group resumed regular estrous cycles after two weeks compared with the normal group, various growth follicles and corpora lutea were observed in ovarian tissues, the number of cystic follicles were reduced, the number of granulosa cell layers was increased, mature follicles were visible, and oocytes were locally intact in morphology, furthermore, the levels of E2 and AMH were reduced in the model group (P<0.05). 3) The continuing model group: Compared with the normal group, the model group was in the late stage of estrous cycle for a long period, and there were more large follicles with cystic dilatation, fewer mature follicles, fewer layers of granulosa cells with sparse and disordered arrangement, the number of corpus luteum was significantly reduced in the ovarian. Furthermore, the levels of serum LH , LH/FSH and T were elevated (P<0.05). Conclusion Subcutaneous injection of 60 mg/kg DHEA for 21 consecutive days can successfully construct a non-obese PCOS rat model that meets clinical characteristics. On this basis, subcutaneous injection of 60 mg/kg DHEA every 48 hours can maintain the stability of the model.

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History
  • Received:November 29,2023
  • Revised:April 02,2024
  • Adopted:May 08,2024
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