RESUMO
Objective:To study the effects of vascular endothelial growth factor (VEGF) inhibitor SU5416 on pulmonary vascular remodeling in neonatal rats with hypoxic pulmonary hypertension (HPH).Methods:Thirty-two neonatal rats (age 7~10 d) were randomly assigned into normoxia group, hypoxia group, SU5416+hypoxia group and SU5416+normoxia group according to corresponding treatments. The endpoint was 14 d after treatments. Right ventricular systolic pressure (RVSP) was measured and cardiac and pulmonary tissue were sampled on the day. Right ventricular hypertrophy index (RVHI) was calculated. After HE staining, the morphological changes of pulmonary vessels were observed under light microscope.Media thickness (MT), external diameter(ED), cross-sectional area of tunica media (MA) and total cross-sectional area(TA) of pulmonary arterioles were measured. MT%(MT/ED) and MA%(MA/TA) were calculated as indicators of pulmonary vascular remodeling. The levels of VEGF and α-smooth muscle actin (α-SMA) in pulmonary vessels were examined using immunohistochemistry (IHC) method.Results:RVSP, RVHI, MT% and MA% in hypoxia group and SU5416+hypoxia group were significantly higher than normoxia group and SU5416+normoxia group ( P<0.05). These indicators in SU5416+hypoxia group were also higher than hypoxia group ( P<0.05),and no significant differences existed between SU5416+normoxia group and normoxia group ( P>0.05). The levels of α-SMA and VEGF in pulmonary vessels in SU5416+hypoxia group and hypoxia group were significantly higher than normoxia group and SU5416+normoxia group ( P<0.05), and α-SMA and VEGF in SU5416+hypoxia group higher than hypoxia group ( P<0.05). Conclusions:VEGF inhibitor SU5416 may exacerbate pulmonary hypertension and increase pulmonary vascular remodeling in neonatal HPH rats.
RESUMO
Objective To study the effects of angiogenesis inhibitor SU5416 on the growth and metastasis to the liver of gastric cancer and to investigate its effect on the apoptosis of gastric cancer cells. Methods Metastatic model simulating human gastric cancer was established by orthotopic implantation of histologically intact human tumor tissue into gastric wall of nude mice. Mice were randomly divided into 4 groups: control group (saline solution), 5 FU group (fluorouracil 30 mg?kg -1 ?d -1 i.p.), SU5416 group (SU5416 15 mg?kg -1 ?d -1 i.p.), and combined treatment of both 5 FU and SU5416 group. Eight weeks after implantation, the tumor weight, inhibition rates, intratumoral microvessel density (MVD), apoptotic index (AI), and the presence of metastasis were evaluated respectively after the mice were sacrificed. Results Compared with the control group, the growth of the orthotopically implanted tumor was significantly inhibited due to the reduced weight and the inhibition rate of tumor was 44.5%, 79.3%, and 84.4% respectively in mice treated with 5 FU, SU5416 and both. The incidences of liver metastases were also significantly decreased in the 5 FU group, SU5416 group, and combined group compared with those in control group (36.4%, 25.0%, and 0% vs 90.0%). The MVD was decreased significantly in the treated mice ( 14.6 ? 5.8 vs 13.1?4.7, 3.9? 1.8 , and 2.1?1.5). The AI was increased significantly in the treated mice [(3.76?2.25)% vs (6.81? 4.92 )%, (9.82?3.76)% and (17.65?9.85)%]. The growth and liver metastasis of human gastric cancer implanted in nude mice were more significantly inhibited in the SU5416 group and combined group than in control group and 5 FU group ( P