ABSTRACT
Objective To investigate the effect of single dose intraosseous injection of simvastatin on tumor vascular structure and function in murine breast cancer. Methods BALB/c mice and 4T1 murine breast cancer cells were used to establish a subcutaneous xenograft model. The mouse model of orthotopic breast cancer received intraosseous injection of a single dose of simvastatin (50 μg) or vehicle only. Frozen tumor tissue sections were prepared for co-immunostained with CD31 andα-SMA. Evans blue dye was injected into the tail vein to observe the vascular permeability. The expression level of HIF-1αwas detected by immunohistochemistry. Results Immunofluorescence dual staining showed that intraosseous injection of simvastatin increased the number of perivascular pericytes in the tumor vessel(P < 0. 05), Evans blue dye content showed that in vivo vessel permeability in the tumor tissue was significantly decreased(P < 0. 05), and the immunohistochemistry results showed that local hypoxic area was significantly improved. Conclusions Single dose intraosseous injection of simvastatin can promote the normalization of tumor vasculature by improving the coverage of pericytes.
ABSTRACT
Objective To explore the effect of single local intraosseous injection of small dose simvastatin on the angiogenesis and cardiac function in rats after myocardial infarction. Methods Adult male Wistar rats were divided into sham operation group, myocardial infarction model group and intraosseous injection of simvastatin 0. 5 mg group ( all n=12 per group) . The left anterior descending branch of coronary artery was ligated to establish a rat model of myocardial infarc-tion. The left ventricular function was evaluated by small animal echocardiography at 4 weeks postoperatively. The rest of the rats were sacrificed, the myocardial infarct size was evaluated by TTC staining, and the myocardial neovascularization was detected by immunofluorescence staining. Results We successfully established the rat model of myocardial infarction. The echocardiography showed that the left ventricular systolic function was decreased significantly at 4 weeks after myocardi-al infarction. Intraosseous injection of simvastatin (0. 5 mg) did not improve the left ventricular function after myocardial infarction in the rats. TTC staining showed that intraosseous injection of simvastatin did not reduce myocardial infarct size. Immunofluorescence staining showed that the myocardial capillary density of simvastatin group was slightly higher than that of myocardial infarction model group, but showing no significant difference between them. Conclusions Intraosseous in-jection of simvastatin 0. 5 mg 24 hours after myocardial infarction cannot significantly promote myocardial angiogenesis, which is believed to be beneficial to the revascularization after ischemia, and thus failed to improve the cardiac function.
ABSTRACT
Objective To investigate the effect of single dose intraosseous injection of simvastatin on tumor vascular structure and function in murine breast cancer. Methods BALB/c mice and 4T1 murine breast cancer cells were used to establish a subcutaneous xenograft model. The mouse model of orthotopic breast cancer received intraosseous injection of a single dose of simvastatin (50 μg) or vehicle only. Frozen tumor tissue sections were prepared for co-immunostained with CD31 andα-SMA. Evans blue dye was injected into the tail vein to observe the vascular permeability. The expression level of HIF-1αwas detected by immunohistochemistry. Results Immunofluorescence dual staining showed that intraosseous injection of simvastatin increased the number of perivascular pericytes in the tumor vessel(P < 0. 05), Evans blue dye content showed that in vivo vessel permeability in the tumor tissue was significantly decreased(P < 0. 05), and the immunohistochemistry results showed that local hypoxic area was significantly improved. Conclusions Single dose intraosseous injection of simvastatin can promote the normalization of tumor vasculature by improving the coverage of pericytes.
ABSTRACT
Objective To explore the effect of single local intraosseous injection of small dose simvastatin on the angiogenesis and cardiac function in rats after myocardial infarction. Methods Adult male Wistar rats were divided into sham operation group, myocardial infarction model group and intraosseous injection of simvastatin 0. 5 mg group ( all n=12 per group) . The left anterior descending branch of coronary artery was ligated to establish a rat model of myocardial infarc-tion. The left ventricular function was evaluated by small animal echocardiography at 4 weeks postoperatively. The rest of the rats were sacrificed, the myocardial infarct size was evaluated by TTC staining, and the myocardial neovascularization was detected by immunofluorescence staining. Results We successfully established the rat model of myocardial infarction. The echocardiography showed that the left ventricular systolic function was decreased significantly at 4 weeks after myocardi-al infarction. Intraosseous injection of simvastatin (0. 5 mg) did not improve the left ventricular function after myocardial infarction in the rats. TTC staining showed that intraosseous injection of simvastatin did not reduce myocardial infarct size. Immunofluorescence staining showed that the myocardial capillary density of simvastatin group was slightly higher than that of myocardial infarction model group, but showing no significant difference between them. Conclusions Intraosseous in-jection of simvastatin 0. 5 mg 24 hours after myocardial infarction cannot significantly promote myocardial angiogenesis, which is believed to be beneficial to the revascularization after ischemia, and thus failed to improve the cardiac function.