Collagen peptide combined with sodium alginate improve intrauterine adhesions in mice by downregulating expression of NLRP3
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1.the Third Affiliated Hospital of Xinxiang Medical University, Xinxiang 453003, China. 2. School of Basic Medical Sciences College of Xinxiang Medical University, Xinxiang 453003. 3. Sanquan College of Xinxiang Medical University, Xinxiang 453003. 4. the Key Laboratory of Medical Tissue Regeneration in Henan Province, Xinxiang 453003. 5. Nantong Yemeng New Material Co., Ltd, Nantong 226000

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    Abstract:

    Objective To investigate the repairing effect and mechanism of collagen peptide (CP) combined with sodium alginate (SA) on endometrial injury. Methods Forty-eight SPF female C57BL/6N mice were randomly divided into sham, model, and CP + SA groups, with 16 mice in each group. In the model group, the intrauterine adhesion model was established by injecting 95% ethanol into the uterine cavity through the cervix to induce endometrial injury. In the sham operation group, 0. 9% normal saline was injected into the uterine cavity. The treatment group was injected with a mixture of CP and SA after injection of 95% ethanol into the uterine cavity. At 7 days after modeling, eight mice in each group were selected to provide samples. HE staining was used to observe pathological changes in mouse uterine tissue. Modified Masson tricolor staining was used to observe endometrial fibrosis. Western Blot was used to measure protein expression levels of proinflammatory factors NLRP3, ASC, caspase-1, IL-1β, and IL-18 in uterine tissues. ELISA were used to measure IL-1β and IL-18 in serum. The remaining eight mice in each group were cohoused in accordance with a male ∶female ratio of 1∶2, and the number of pregnant mice in each group was recorded. Pregnant mice were euthanized on day 14 of pregnancy, and the number of embryos was recorded. Results (1) Compared with the sham operation group, the model group had a thinner endometrial thickness and increased endometrial fibrosis and inflammatory cell infiltration. Additionally, the protein expression levels of proinflammatory factors NLRP3, ASC, Caspase-1, IL-1β, and IL-18 in uterine tissue and the serum levels of IL-1β and IL-18 in the model group were significantly lower than those in the sham operation group (P< 0. 05). (2) Compared with the model group, the treatment group showed reductions in the degree of endometrial injury, endometrial fibrosis, and inflammatory cell infiltration. Additionally, the protein expression levels of NLRP3, ASC, Caspase-1, IL-1β, and IL-18 in uterine tissue and the serum levels of IL-1β and IL-18 in the model group were significantly lower than those in the sham operation group (P< 0. 05). (3) Compared with the sham group, the reproductive ability of the model group was decreased (P< 0. 01). Compared with the model group, the reproductive ability of the treatment group was significantly improved (P< 0. 01). Conclusions Combined application of CP and SA effectively improved pathological changes of uterine tissue, reduced endometrial injury, inflammatory responses and fibrosis, and improved the reproductive ability of mice. The mechanism may be related to downregulation of NLRP3 inflammasome expression, which provides a reliable experimental basis for combined application of CP and SA for treatment of intrauterine adhesion.

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History
  • Received:May 03,2023
  • Online: December 29,2023
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