【Animal modeling】-Effect of hypoxic preconditioning on the formation of endometriotic lesions in rats

  Objective: To understand the effect of hypoxic preconditioning on the formation of ectopic lesions in a rat model of endometriosis (EMs), so as to further clarify the molecular mechanism of the occurrence and development of EMs, so as to provide new ideas for its prevention and treatment.

  Methods: Lewis female rats were randomly divided into two groups and treated with HPC (8% O2) and normobaric normoxic (21% O2) for 8 h, and then the uterine tissue was harvested and transplanted to the abdominal wall of normal rats. The volume of the transplanted foci was recorded 14 days after the operation, and the serum and peritoneal fluid, as well as the uterine tissue and transplanted foci before transplantation were detected by ELISA, immunohistochemistry, Western blot, RT-PCR and Tunnel method.

  Results: HPC could significantly up-regulate vascular endothelial growth factor (VEGF) mRNA (P<0.01) and increase the expression of hypoxia-inducible factor (HIF)-α (P<0.01) in rat uterus; The volume of transplanted lesions formed by HPC uterine tissue was significantly increased (P<0.01), the apoptosis rate of tissue cells was decreased (P<0.01), VEGF mRNA was up-regulated (P<0.01), HIF-α (P<0.01), The expressions of VEGF (P<0.05), CD31 (P<0.01), Ki67 (P<0.01) and Bcl-2 (P<0.05) were significantly increased; and the serum and ascites VEGF of rats transplanted with HPC uterine tissue The content also increased significantly (P<0.01).

  Conclusion: HPC can promote angiogenesis in transplanted lesions by activating the HIF-1α/VEGF system; and by up-regulating the expression of Bcl-2 anti-apoptotic factor, inhibiting the apoptosis of transplanted lesions and promoting its proliferation, thereby promoting the growth of transplanted lesions. grow. Based on this, we speculate that for high-risk subjects or patients with recurrent EMs, avoiding repeated hypoxic stimulation of eutopic endometrial tissue, and artificially intervening to inhibit the activation of HIFs/VEGF system before endometrial tissue shedding is expected to control the occurrence of EMs. one of the measures of development.