The aims of the present study were to determine the effects of heparin-derived oligosaccharides(HDOs) on vascular intimal hyperplasia(IH) in balloon-injured carotid artery and to elucidate the underlying mechanisms of...The aims of the present study were to determine the effects of heparin-derived oligosaccharides(HDOs) on vascular intimal hyperplasia(IH) in balloon-injured carotid artery and to elucidate the underlying mechanisms of action. An animal model was established by rubbing the endothelia within the common carotid artery(CCA) in male rabbits. The rabbits were fed a high-cholesterol diet. Arterial IH was determined by histopathological changes to the CCA. Serum lipids were detected using an automated biochemical analysis. Expressions of mR NAs for vascular endothelial growth factor(VEGF), basic fibroblast growth factor(bF GF), vascular cell adhesion molecule-1(VCAM-1), monocyte chemoattractant protein-1(MCP-1), scavenger receptor class B type I(SR-BI), and ATP-binding cassette transporter A1(ABCA-1) were analyzed using reverse transcription polymerase chain reaction assays. Expressions of VEGF, VCAM-1, MCP-1, SR-BI and ABCA-1 proteins were analyzed by Western blotting. Enzyme-linked immunosorbent assays were used to quantify expression levels of VEGF and b FGF. Our results showed that administration of HDO significantly inhibited CCA histopathology and restenosis induced by balloon injury. The treatment with HDOs significantly decreased the m RNA and protein expression levels of VEGF, b FGF, VCAM-1, MCP-1, and SR-BI in the arterial wall; however, ABCA-1 expression level was elevated. HDO treatment led to a reduction in serum lipids(total cholesterol, triglycerides, high-density and low-density lipoproteins). Our results from the rabbit model indicated that HDOs could ameliorate IH and underlying mechanism might involve VEGF, b FGF, VCAM-1, MCP-1, SR-BI, and ABCA-1.展开更多
Objective： To investigate the effect and potential mechanisms of rutaecarpine （Rut） in a rat artery balloon-injury model. Methods： The intimal hyperplasia model was established by rubbing the endothelia with a bal...Objective： To investigate the effect and potential mechanisms of rutaecarpine （Rut） in a rat artery balloon-injury model. Methods： The intimal hyperplasia model was established by rubbing the endothelia with a balloon catheter in the common carotid artery （CCA） of rats. Fifty rats were randomly divided into five groups, ie. sham, model, Rut （25, 50 and 75 mg/kg） with 10 rats of each group. The rats were treated with or without Rut （25, 50, 75 mg/kg） by intragastric administration for 14 consecutive days following injury. The morphological changes of the intima were evaluated by hematoxylin-eosin staining. The expressions of proliferating cell nuclear antigen （PCNA） and smooth muscle （SM） oL-actin in the ateries were assayed by immunohistochemical staining. The mRNA expressions of c-myc, extracellular signal-regulated kinase 2 （ERK2）, MAPK phosphatase-1 （MKP-1） and endothelial nitric oxide synthase （eNOS） were determined by real-time reverse chain reaction. The protein expressions of MKP-1 and phosphorylated ERK2 （p-ERK2） were examined by Western blotting. The plasma contents of nitric oxide （NO） and cyclic guanosine 3＇,5＇-monophosphate （cGMP） were also determined. Results： Compared with the model group, Rut treatment significantly decreased intimal thickening and ameliorated endothelial injury （P〈0.05 or P〈0.01）. The positive expression rate of PCNA was decreased, while the expression rate of SM α -actin obviously increased in the vascular wall after Rut （50 and 75 mg/kg） administration （P〈0.05 or P〈0.01）. Furthermore, the mRNA expressions of c-myc, ERK2 and PCNA were downregulated while the expressions of eNOS and MKP-1 were upregulated （P〈0.05 or P〈0.01）. The protein expressions of MKP-1 and the phosphorylation of ERK2 were upregulated and downragulated after Rut （50 and 75 mg/kg） administration （P〈0.05 or P〈0.01）, respectively. In addition, Rut dramatically reversed balloon injury-induced decrease of NO and cGMP in the plasma （P〈0.05 or P〈0.01）. Conclusion： Rut could inhibit the balloon injury-induced carotid intimal hyperplasia in rats, possibly mediated by promotion of NO production and inhibiting ERK2 signal transduction pathways.展开更多
【目的】研究Caspase-1特异性抑制剂AC-YVAD-CMK对大鼠颈动脉球囊损伤后血管内膜增生的影响及可能机制。【方法】33只雄性成年SD大鼠,随机均分为假手术组、球囊损伤组、球囊损伤+AC-YVAD-CMK组。采用球囊损伤大鼠颈动脉的方法建立血管...【目的】研究Caspase-1特异性抑制剂AC-YVAD-CMK对大鼠颈动脉球囊损伤后血管内膜增生的影响及可能机制。【方法】33只雄性成年SD大鼠,随机均分为假手术组、球囊损伤组、球囊损伤+AC-YVAD-CMK组。采用球囊损伤大鼠颈动脉的方法建立血管内膜增生动物模型,14天后留取球囊损伤段血管,15个血管片段制作冰冻切片,苏木精-伊红(HE)染色法测量内膜与中膜(I/M)面积比值;18根血管片段采用Western blot检测NOD样受体蛋白3(NLRP3)炎症小体、cleaved-Caspase-1、白介素(IL)-1β和IL-18的表达。【结果】HE染色发现,AC-YVAD-CMK显著抑制了内膜增生的程度(0.78±0.13 vs 1.52±0.14,P=0.000)。Western blot结果提示球囊损伤+AC-YVAD-CMK组中NLRP3蛋白表达较球囊损伤组显著降低(P=0.009);cleaved-Caspase-1蛋白在三组中的表达趋势与NLRP3蛋白表达一致(P=0.000)。且球囊损伤+AC-YVAD-CMK组大鼠的促炎性细胞因子IL-1β和IL-18水平较球囊损伤组显著降低(P=0.000)。【结论】AC-YVAD-CMK可以抑制大鼠颈动脉球囊损伤后内膜增生,其机制可能是其阻断Caspase-1蛋白活化,从而抑制促炎因子IL-1β和IL-18的释放而产生一定的保护作用。展开更多
基金supported by the National Basic Research Funds(Nos.JKYJ2013044 and JKZ2011013)the Significant New Drugs Innovation Support Program of the National Science and Technology Project of China(No.2012ZX09502001-004)the Priority Academic Program Development of Jiangsu Higher Education Institution
文摘The aims of the present study were to determine the effects of heparin-derived oligosaccharides(HDOs) on vascular intimal hyperplasia(IH) in balloon-injured carotid artery and to elucidate the underlying mechanisms of action. An animal model was established by rubbing the endothelia within the common carotid artery(CCA) in male rabbits. The rabbits were fed a high-cholesterol diet. Arterial IH was determined by histopathological changes to the CCA. Serum lipids were detected using an automated biochemical analysis. Expressions of mR NAs for vascular endothelial growth factor(VEGF), basic fibroblast growth factor(bF GF), vascular cell adhesion molecule-1(VCAM-1), monocyte chemoattractant protein-1(MCP-1), scavenger receptor class B type I(SR-BI), and ATP-binding cassette transporter A1(ABCA-1) were analyzed using reverse transcription polymerase chain reaction assays. Expressions of VEGF, VCAM-1, MCP-1, SR-BI and ABCA-1 proteins were analyzed by Western blotting. Enzyme-linked immunosorbent assays were used to quantify expression levels of VEGF and b FGF. Our results showed that administration of HDO significantly inhibited CCA histopathology and restenosis induced by balloon injury. The treatment with HDOs significantly decreased the m RNA and protein expression levels of VEGF, b FGF, VCAM-1, MCP-1, and SR-BI in the arterial wall; however, ABCA-1 expression level was elevated. HDO treatment led to a reduction in serum lipids(total cholesterol, triglycerides, high-density and low-density lipoproteins). Our results from the rabbit model indicated that HDOs could ameliorate IH and underlying mechanism might involve VEGF, b FGF, VCAM-1, MCP-1, SR-BI, and ABCA-1.
基金Supported by National Natural Science Foundation of China(No.81160528)Administration of Traditional Chinese Medicine of Guizhou Province foundation,China(No.2009-79)
文摘Objective： To investigate the effect and potential mechanisms of rutaecarpine （Rut） in a rat artery balloon-injury model. Methods： The intimal hyperplasia model was established by rubbing the endothelia with a balloon catheter in the common carotid artery （CCA） of rats. Fifty rats were randomly divided into five groups, ie. sham, model, Rut （25, 50 and 75 mg/kg） with 10 rats of each group. The rats were treated with or without Rut （25, 50, 75 mg/kg） by intragastric administration for 14 consecutive days following injury. The morphological changes of the intima were evaluated by hematoxylin-eosin staining. The expressions of proliferating cell nuclear antigen （PCNA） and smooth muscle （SM） oL-actin in the ateries were assayed by immunohistochemical staining. The mRNA expressions of c-myc, extracellular signal-regulated kinase 2 （ERK2）, MAPK phosphatase-1 （MKP-1） and endothelial nitric oxide synthase （eNOS） were determined by real-time reverse chain reaction. The protein expressions of MKP-1 and phosphorylated ERK2 （p-ERK2） were examined by Western blotting. The plasma contents of nitric oxide （NO） and cyclic guanosine 3＇,5＇-monophosphate （cGMP） were also determined. Results： Compared with the model group, Rut treatment significantly decreased intimal thickening and ameliorated endothelial injury （P〈0.05 or P〈0.01）. The positive expression rate of PCNA was decreased, while the expression rate of SM α -actin obviously increased in the vascular wall after Rut （50 and 75 mg/kg） administration （P〈0.05 or P〈0.01）. Furthermore, the mRNA expressions of c-myc, ERK2 and PCNA were downregulated while the expressions of eNOS and MKP-1 were upregulated （P〈0.05 or P〈0.01）. The protein expressions of MKP-1 and the phosphorylation of ERK2 were upregulated and downragulated after Rut （50 and 75 mg/kg） administration （P〈0.05 or P〈0.01）, respectively. In addition, Rut dramatically reversed balloon injury-induced decrease of NO and cGMP in the plasma （P〈0.05 or P〈0.01）. Conclusion： Rut could inhibit the balloon injury-induced carotid intimal hyperplasia in rats, possibly mediated by promotion of NO production and inhibiting ERK2 signal transduction pathways.
文摘【目的】研究Caspase-1特异性抑制剂AC-YVAD-CMK对大鼠颈动脉球囊损伤后血管内膜增生的影响及可能机制。【方法】33只雄性成年SD大鼠,随机均分为假手术组、球囊损伤组、球囊损伤+AC-YVAD-CMK组。采用球囊损伤大鼠颈动脉的方法建立血管内膜增生动物模型,14天后留取球囊损伤段血管,15个血管片段制作冰冻切片,苏木精-伊红(HE)染色法测量内膜与中膜(I/M)面积比值;18根血管片段采用Western blot检测NOD样受体蛋白3(NLRP3)炎症小体、cleaved-Caspase-1、白介素(IL)-1β和IL-18的表达。【结果】HE染色发现,AC-YVAD-CMK显著抑制了内膜增生的程度(0.78±0.13 vs 1.52±0.14,P=0.000)。Western blot结果提示球囊损伤+AC-YVAD-CMK组中NLRP3蛋白表达较球囊损伤组显著降低(P=0.009);cleaved-Caspase-1蛋白在三组中的表达趋势与NLRP3蛋白表达一致(P=0.000)。且球囊损伤+AC-YVAD-CMK组大鼠的促炎性细胞因子IL-1β和IL-18水平较球囊损伤组显著降低(P=0.000)。【结论】AC-YVAD-CMK可以抑制大鼠颈动脉球囊损伤后内膜增生,其机制可能是其阻断Caspase-1蛋白活化,从而抑制促炎因子IL-1β和IL-18的释放而产生一定的保护作用。
