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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.
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Objective To investigate the effects of vitamin D on synthesis and secretion of lubricin in chondrocytes at the cellular level. Methods Rat articular chondrocytes were stimulated by TNF-α. Normal and inflammatory chondrocytes were treated by different doses of vitamin D respectively. ELISA and Western Blot were used to detect the secretion of lubricin in the supernatant and the synthesis level in the cells. Results TNF-α significantly reduced the activity of both normal chondrocytes and chondrocytes in inflammatory state. TNF-α also significantly reduced the expression of lubricin in the cells and supernatant. 1α,25(OH)2D3 increased the activity of both normal chondrocytes and chondrocytes in inflammatory state. 1α,25(OH)2D3 significantly elevated the secretion and expression of supernatant and intracellular lubricin only in chondrocytes stimulated by TNF-α in a dose-dependent manner, but not in normal chondrocytes. Conclusions Vitamin D can promote the secretion and expression of lubricin in inflammatory state chondrocytes, which may act as one of the mechanisms of vitamin D protecting the cartilage surface in osteoarthritis.
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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.
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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.
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Objective To investigate the effects of vitamin D on synthesis and secretion of lubricin in chondrocytes at the cellular level. Methods Rat articular chondrocytes were stimulated by TNF-α. Normal and inflammatory chondrocytes were treated by different doses of vitamin D respectively. ELISA and Western Blot were used to detect the secretion of lubricin in the supernatant and the synthesis level in the cells. Results TNF-α significantly reduced the activity of both normal chondrocytes and chondrocytes in inflammatory state. TNF-α also significantly reduced the expression of lubricin in the cells and supernatant. 1α,25(OH)2D3 increased the activity of both normal chondrocytes and chondrocytes in inflammatory state. 1α,25(OH)2D3 significantly elevated the secretion and expression of supernatant and intracellular lubricin only in chondrocytes stimulated by TNF-α in a dose-dependent manner, but not in normal chondrocytes. Conclusions Vitamin D can promote the secretion and expression of lubricin in inflammatory state chondrocytes, which may act as one of the mechanisms of vitamin D protecting the cartilage surface in osteoarthritis.
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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.
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<p><b>OBJECTIVE</b>To investigate effect of pinacidil, an ATP sensitive potassium channel (K(ATP)) opener, on the neuronal apoptosis and its signaling transduction mechanism following focal cerebral ischemia-reperfusion in rats.</p><p><b>METHODS</b>One hundred male Wistar rats were randomly divided into four groups: A, sham-operated group; B, ischemia-reperfusion group; C, K(ATP) opener treatment group; and D, K(ATP) opener and blocker treatment group. The middle cerebral artery occlusion (MCAO) model was established by using the intraluminal suture occlusion method, neuronal apoptosis was determined by TUNEL staining, and expressions of caspase-8, caspase-9 and caspase-3 mRNA were detected by in situ hybridization.</p><p><b>RESULTS</b>(1) The numbers of apoptotic neurons at 12 h, 24 h, 48 h, and 72 h were significantly less in group C than in groups B and D (P< 0.01 or P< 0.05); and there was no difference between groups B and D at all time points (P> 0.05). (2) The expressions of caspase-3 mRNA and caspase-8 mRNA at all times and the expressions of caspase-9 mRNA at 12 h, 24 h, 48 h, 72 h were significantly lower in group C than in groups B and D (P< 0.01 or P< 0.05); and there were no differences between groups B and D at all time points (P> 0.05).</p><p><b>CONCLUSIONS</b>K(ATP) opener can significantly decrease the neuronal apoptosis and the expressions of caspase-3, caspase-8 and caspase-9 mRNAs following cerebral ischemia-reperfusion. The neuronal apoptosis may be decreased by the inhibition of both mitochondrial and death-receptor signal pathways.</p>
Subject(s)
Animals , Male , Rats , Antihypertensive Agents , Therapeutic Uses , Apoptosis , Brain Ischemia , Drug Therapy , Caspases , Metabolism , Gene Expression Regulation , In Situ Nick-End Labeling , Neurons , Pinacidil , Therapeutic Uses , RNA, Messenger , Metabolism , Rats, Wistar , Reperfusion Injury , Drug Therapy , Time FactorsABSTRACT
Aim To study the expression of caspase-12 mRNA and protein following focal cerebral ischemia-reperfusion in rats,and explore the effect of endoplasmic reticulum pathway on neuronal apoptosis.Methods 60 male Wistar rats were randomly divided into sham-operated group and ischemic group.The middle cerebral artery occlusion(MCAO)models were established by using the intraluminal suture occlusion method,neuronal apoptosis was detected by TUNEL staining,the expression of caspase-12 protein was detected by immunohistochemical staining,the expression of caspase-12 mRNA was detected by RT-PCR method.Results In ischemic group,the number of apoptotic cells and the expression of caspase-12 mRNA and protein were gradually increased following prolonged cerebral reperfusion,reached the peak at 24 h.The number of apoptotic cells and the expression of caspase-12 mRNA and protein in ischemic group were significantly less than those of sham-operated group at all times(P