Abstract

ZHAO, Danyang; BAO, Qiufang; CHEN, Lihong  and  ZHENG, Lie. Effects of SU5416 on angiogenesis and the ERK-VEGF/MMP-9 pathway in rat endometriosis. Invest. clín [online]. 2023, vol.64, n.4, pp.482-494.  Epub Dec 23, 2023. ISSN 0535-5133.  https://doi.org/10.54817/ic.v64n4a05.

SU5416 is a small molecule vascular endothelial growth factor (VEGF) receptor signal transduction inhibitor, which can block the VEGF receptor autophosphorylation and inhibit receptor tyrosine kinase signal transduction, thereby reducing VEGF activity. However, there are few reports about the correlation of SU5416 to the occurrence and angiogenesis in endometriosis. In this study, we observed the effects of VEGF receptor inhibitor SU5416 on angiogenesis in endometriosis in rats. Thirty female specific-pathogen-free Sprague-Dawley rats were randomly divided into sham operation group (SOG), model group (MG), and SU5416 group (n=10 for each group). In the SOG, only the uterus was cut and sutured, and endometriosis models were established in the MG and SU5416 group by autologous transplantation. The SU5416 group was injected with 15 mg/kg SU5416 intraperitoneally, and the SOG and MG were intraperitoneally injected with an equal volume of normal saline for 6 weeks. The volume of ectopic lesions was lower in the SU5416 group at 42 d postoperatively than in the MG (p<0.05). The proportion of CD31-positive cells in the endometrial tissue of the SU5416 group was lower than that of the MG (p<0.05); angiopoietin-1 (Ang-1), angiopoietin-2 (Ang-2), laminin-5γ2 (LN-5γ2) and phosphorylation of ERK (P-ERK), VEGF, matrix metalloproteinase (MMP)-2, and MMP-9 protein expressions were lower in the SU5416 group than in the MG (p<0.05). VEGF receptor inhibitor SU5416 can inhibit endometriosis angiogenesis and reduce inflammatory response in rats, and its mechanism of action may be related to the down-regulation of the ERK-VEGF/MMP-9 pathway expression.

Keywords : angiogenesis; endometriosis; ERK-VEGF/MMP-9 pathway; SU5416.

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