RESUMEN
BACKGROUND Bariatric procedures such as left gastric artery ligation (LGAL) and sleeve gastrectomy (SG) have emerged as important procedures for treating morbid obesity. In this study, we compared the effects of LGAL vs. SG on obesity-induced adipose tissue macrophage infiltration and inflammation in diet-induced obese rats. MATERIAL AND METHODS Sprague-Dawley (SD) rats were fed a high-fat diet (HFD) for 16 weeks to induce obesity. SG, GLAL, or corresponding sham surgeries were performed in anesthetized rats. Inflammatory factor expression in serum and epididymal and retroperitoneal adipose tissues were analyzed 4 weeks after surgery. Macrophage infiltration and phenotype transformation were also assessed with Western blot analysis and immunofluorescence. RESULTS Both LGAL and SG strongly attenuated high-fat diet (HFD)-induced fat accumulation in retroperitoneal and epididymal tissues. The expressions of inflammatory cytokines such as tumor necrosis factor (TNF)-alpha, interleukin (IL)-6, and monocyte chemoattractant protein (MCP)-1 were downregulated after LGAL and after SG by promoting activation of M2 macrophages, despite continued exposure to HFD. Furthermore, both LGAL and SG resulted in increased macrophage infiltration, but did not contribute to phenotype transformation of macrophages to M1. CONCLUSIONS LGAL and SG both reduced fat accumulation caused by HFD feeding. Therapies designed to ameliorate the inflammatory response by promoting activation of M2 macrophages may be valuable.
Asunto(s)
Tejido Adiposo/patología , Dieta Alta en Grasa , Gastrectomía , Artería Gástrica/ultraestructura , Inflamación/patología , Macrófagos/patología , Obesidad/patología , Animales , Epidídimo/patología , Mediadores de Inflamación/metabolismo , Proteínas Sustrato del Receptor de Insulina/metabolismo , Ligadura , Masculino , FN-kappa B/metabolismo , Fosforilación , Proteínas Proto-Oncogénicas c-akt/metabolismo , Ratas Sprague-Dawley , Transducción de SeñalRESUMEN
OBJECTIVE: To study the expression of matrix metalloproteinase (MMP)-2, MMP-9 and vascular endothelial growth factor (VEGF)-C in breast cancer and their role in lymph node metastasis. METHODS: Immunohistochemical staining was used to detect the expression of VEGF-C, MMP-2, MMP-9 and LYVE-1 in 84 cases of breast cancer, including 52 cases with and 32 cases without lymph node metastases. The recombinant vector (pSIREN-VEGF-C) was transfected into human breast cancer cell MCF-7 by liposome, and the RNA expression of MMP-2, MMP-9 and VEGF-C in MCF-7 cells after transfection was detected by PCR. RESULTS: The expressions of MMP-2, MMP-9 and VEGF-C were 98.1% (51/52), 88.5% (46/52), and 94.2% (49/52) respectively for the metastatic group, and 75.0% (24/32), 53.1% (17/32), and 65.6% (21/32) respectively for the non metastatic group, and there was significant difference between these groups (P < 0.05). The lymphatic vessel density between these two groups was also significantly different (P < 0.05). Increased expression of MMP-2, MMP-9 and VEGF-C was also associated with increased number of lymphatic vessels had also increased (P < 0.05). The expression of MMP-2, MMP-9 and VEGF-C in MCF-7 cells after gene transfection decreased significantly (P < 0.05). CONCLUSION: MMP-2 and MMP-9 in conjunction with VEGF-C, promote lymphangiogenesis and lymph node metastasis of breast cancer.