Collagen peptide combined with sodium alginate improved intrauterine adhesions in mice by down-regulating the expression of NLRP3 inflammasome
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1.Xinxiang Medical University;2.Xinxiang Medical University,Sanquan College of Xinxiang Medical College;3.The Third Affiliated Hospital of Xinxiang Medical University;4.Nantong Yemeng New Material Co., Ltd

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Found by the National Key R & D Program Grant (2018YFC1105800), Nantong Yemeng New Material Co., Ltd Yemeng Foundation (110202002), Open Project of the Third Affiliated Hospital of Xinxiang Medical University (KFKTYB202127) and Postgraduate Scientific Research Innovation Support Program of Xinxiang Medical University (YJSCX202124Z).

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    Abstract:

    【Abstract】Objective To investigate the repair effect and mechanism of collagen peptides (CP) combined with sodium alginate (SA) on endometrial injury. Methods Forty-eight SPF female C57BL/6N mice were randomly divided into sham group (16 mice), model group (16 mice) and CP SA group (16 mice). In the model group, 95% ethanol was injected into the uterine cavity through the cervix to induce endometrial injury, and the intrauterine adhesion model was established. The sham operation group was injected with 0.9% normal saline into the uterine cavity. The treatment group was injected with the mixture of CP SA after the injection of 95% ethanol into the uterine cavity. After 7 days of modeling, 8 mice in each group were selected to collect samples for each test. HE staining was used to observe the pathological changes of mouse uterine tissue. Modified Masson tri-color staining was used to observe endometrial fibrosis. Western blot was used to detect the protein expression levels of inflammatory factors NLRP3, ASC, Caspase-1, IL-1β and IL-18 in uterine tissues. ELISA was used to detect the expression of IL-1β and IL-18 in serum. The remaining 8 mice in each group were cohoused according to the male-female ratio of 1:2, and the number of pregnant mice in each group was recorded. Pregnant mice were euthanized in the 14th day of pregnancy, and the number of embryos was recorded. Results (1) Compared with the sham operation group, the model group showed thinner endometrial thickness, increased endometrial fibrosis, and inflammatory cell infiltration. In addition, the protein expression levels of inflammatory factors NLRP3, ASC, Caspase-1, IL-1β and IL-18 in uterine tissue and the levels of IL-1β and IL-18 in serum 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 that the degree of endometrial injury, endometrial fibrosis and inflammatory cell infiltration were reduced. In addition, the protein expression levels of inflammatory factors NLRP3, ASC, Caspase-1, IL-1β and IL-18 in uterine tissue and the levels of IL-1β and IL-18 in serum in the model group were significantly decreased than those in the sham operation group (P< 0.05). (3) Compared with the sham group, the reproductive ability of the model group decreased (P<0.05). Compared with the model group, the reproductive ability of the treatment group was significantly improved(P<0.05). Conclusions The combined application of CP and SA can effectively improve the pathological changes of uterine tissue, reduce endometrial injury, inflammatory response and fibrosis, and improve the reproductive ability of mice. The mechanism may be related to the down-regulation of NLRP3 inflammasome expression, which provides a reliable experimental basis for the combined application of CP and SA in the treatment of intrauterine adhesion.

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History
  • Received:May 03,2023
  • Revised:September 15,2023
  • Adopted:September 15,2023
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