丹酚酸B对糖尿病大鼠血管舒张功能、NF-κB活化及炎症因子表达的影响
|
摘要
目的:研究丹酚酸B对糖尿病大鼠血管舒张功能的改善作用及其可能机制。方法:SD大鼠40只,采用高糖高脂饮食联合腹腔注射链脲佐菌素方法建立糖尿病大鼠模型(随机血糖>16.7 mmol/L)。将糖尿病大鼠随机分为模型组、Sal B高剂量(160 mg·kg~(-1)·d~(-1))组和Sal B低剂量(80 mg·kg-1·d-1)组,另取10只正常大鼠作为对照组。丹酚酸B组每日灌胃给予相应剂量丹酚酸B,共6周。采用离体动脉环实验检测血管舒张功能,HE染色观察大鼠主动脉病理学变化,ELISA法测定血清白细胞介素6(IL-6)、肿瘤坏死因子α(TNF-α)及C反应蛋白(CRP)水平,比色法测定血管组织中总抗氧化能力、丙二醛(MDA)和一氧化氮(NO)水平,Western blot法检测主动脉细胞间黏附分子1(ICAM-1)和单核细胞趋化因子1(MCP-1)的蛋白表达水平以及核因子κB(NF-κB)的活化水平。结果:丹酚酸B明显减轻糖尿病大鼠主动脉病变,改善血管舒张功能,提高血管组织总抗氧化能力和NO水平,降低组织MDA以及血清IL-6、TNF-α和CRP水平(P<0.05或P<0.01),并减少主动脉NF-κB p65亚基核转位及ICAM-1和MCP-1蛋白表达水平(P<0.05或P<0.01)。结论:丹酚酸B可明显改善糖尿病大鼠血管舒张功能,其机制可能与改善机体氧化应激状态、抑制NF-κB活化而减轻血管炎性病变有关。
AIM:To investigate the ameliorative effect of salvianolic acid B on vasodilatory function in diabetic rats and the possible mechanisms.METHODS:SD rats(n=40)were fed on high-sugar and high-fat diet for 4 weeks,followed by a single intraperitoneal injection of streptozotocin(40 mg/kg).The rats with random blood glucose level over16.7 mmol/L were considered diabetic and randomly allocated to 3 groups,namely model group,low dose(80 mg·kg~(-1)·d~(-1))of salvianolic acid B group and high dose(160 mg·kg~(-1)·d~(-1))of salvianolic acid B group.The rats in salvianolic acid B groups were intragastrically administered with corresponding doses of salvianolic acid B for 6 weeks.Vasodilatory function was measured as endothelium-dependent and-independent vasodilation of the aortic rings.The primary histopathological changes of aorta were observed by HE staining.Serum levels of interleukin-6(IL-6),tumor necrosis factor-α(TNF-α)and C-reactive protein(CRP)were measured by ELISA.The levels of total antioxidant capacity,malondialdehyde(MDA)and nitric oxide(NO)in aortic tissues were evaluated by colorimetric assays.The protein levels of intercellular adhesion molecule-1(ICAM-1)and monocyte chemotactic protein-1(MCP-1),and the activation of nuclear factor-κB(NF-κB)were determined by Western blot.RESULTS:Treatment with salvianolic acid B evidently ameliorated endothelium-dependent diastolic function and pathological changes of aorta in diabetic rats(P<0.05 or P<0.01).Supplementation with salvianolic acid B resulted in significant increases in NO content and total antioxidant capacity in aortic tissues,accompanied by marked decreases in the level of MDA in aorta tissues and the serum levels of IL-6,TNF-αand CRP(P<0.05 or P<0.01).Salvianolic acid B markedly down-regulated NF-κB p65 nuclear translocation and protein expression of ICAM-1 and MCP-1 in aorta tissues(P<0.05 or P<0.01).CONCLUSION:Salvianolic acid B effectively ameliorates endothelium-dependent diastolic function of aorta in diabetic rats,which might be attributed to suppression of NF-κB activation and subsequent expression of inflammatory cytokines.The beneficial effect of salvianolic acid B on vascular endothelium might be derived from its antioxidant capacity.
AIM:To investigate the ameliorative effect of salvianolic acid B on vasodilatory function in diabetic rats and the possible mechanisms.METHODS:SD rats(n=40)were fed on high-sugar and high-fat diet for 4 weeks,followed by a single intraperitoneal injection of streptozotocin(40 mg/kg).The rats with random blood glucose level over16.7 mmol/L were considered diabetic and randomly allocated to 3 groups,namely model group,low dose(80 mg·kg~(-1)·d~(-1))of salvianolic acid B group and high dose(160 mg·kg~(-1)·d~(-1))of salvianolic acid B group.The rats in salvianolic acid B groups were intragastrically administered with corresponding doses of salvianolic acid B for 6 weeks.Vasodilatory function was measured as endothelium-dependent and-independent vasodilation of the aortic rings.The primary histopathological changes of aorta were observed by HE staining.Serum levels of interleukin-6(IL-6),tumor necrosis factor-α(TNF-α)and C-reactive protein(CRP)were measured by ELISA.The levels of total antioxidant capacity,malondialdehyde(MDA)and nitric oxide(NO)in aortic tissues were evaluated by colorimetric assays.The protein levels of intercellular adhesion molecule-1(ICAM-1)and monocyte chemotactic protein-1(MCP-1),and the activation of nuclear factor-κB(NF-κB)were determined by Western blot.RESULTS:Treatment with salvianolic acid B evidently ameliorated endothelium-dependent diastolic function and pathological changes of aorta in diabetic rats(P<0.05 or P<0.01).Supplementation with salvianolic acid B resulted in significant increases in NO content and total antioxidant capacity in aortic tissues,accompanied by marked decreases in the level of MDA in aorta tissues and the serum levels of IL-6,TNF-αand CRP(P<0.05 or P<0.01).Salvianolic acid B markedly down-regulated NF-κB p65 nuclear translocation and protein expression of ICAM-1 and MCP-1 in aorta tissues(P<0.05 or P<0.01).CONCLUSION:Salvianolic acid B effectively ameliorates endothelium-dependent diastolic function of aorta in diabetic rats,which might be attributed to suppression of NF-κB activation and subsequent expression of inflammatory cytokines.The beneficial effect of salvianolic acid B on vascular endothelium might be derived from its antioxidant capacity.
引文
[1]李秀钧.2型糖尿病防治策略的革命——从降糖治疗到全面防治心血管危险因素[J].中华内科杂志,2002,41(4):217-218.
[2]Ojima A,Ishibashi Y,Matsui T,et al.Glucagon-like peptide-1 receptor agonist inhibits asymmetric dimethylarginine generation in the kidney of streptozotocin-induced diabetic rats by blocking advanced glycation end productinduced protein arginine methyltrans ferase-1 expression[J].Am J Pathol,2013,182(1):132-141.
[3]Giacco F,Brownlee M.Oxidative stress and diabetic complications[J].Circ Res,2010,107(9):1058-1070.
[4]Joe Y,Zheng M,Kim HJ,et al.Salvianolic acid B exerts vasoprotective effects through the modulation of heme oxygenase-1 and arginase activities[J].J Pharmacol Exp Ther,2012,341(3):850-858.
[5]魏聪.糖尿病大血管病变的研究进展[J].上海交通大学学报:医学版,2010,30(10):1292-1295.
[6]Pradhan AD,Ridker PM.Do atherosclerosis and type 2diabetes share a common inflammatory basis?[J].Eur Heart J,2002,23(11):831-834.
[7]Mohammad Shahi M,Zakerzadeh M,Zakerkish M,et al.Effect of sesamin supplementation on glycemic status,inflammatory markers,and adiponectin levels in patients with type 2 diabetes mellitus[J].J Dietary Supplements,2017,14(1):65-75.
[8]Kolseth IB,Reine TM,Parker K,et al.Increased levels of inflammatory mediators and proinflammatory monocytes in patients with type I diabetes mellitus and nephropathy[J].J Diabetes Complications,2017,31(1):245-252.
[9]张安邦,高杰,李令根,等.相关炎症因子与动脉粥样硬化的关系[J].中国中西医结合外科杂志,2014,20(5):563-566.
[10]王晓晨,吉爱国.NF-κB信号通路与炎症反应[J].生理科学进展,2014,45(1):68-71.
[11]刘俊田.动脉粥样硬化发病的炎症机制的研究进展[J].西安交通大学学报:医学版,2015,36(2):141-152.
[12]郭丽婷,高志红,葛焕琦.2型糖尿病患者外周血micro RNA-155、细胞核因子-κB和可溶性细胞间黏附分子-1的表达及其与血管并发症的关系研究[J].中国糖尿病杂志,2017,25(3):213-217.
[13]刘江月.降糖调脂灵抑制核因子κB核转位对T2DM血管内皮的损伤作用[J].时珍国医国药,2015,26(3):567-570.
[2]Ojima A,Ishibashi Y,Matsui T,et al.Glucagon-like peptide-1 receptor agonist inhibits asymmetric dimethylarginine generation in the kidney of streptozotocin-induced diabetic rats by blocking advanced glycation end productinduced protein arginine methyltrans ferase-1 expression[J].Am J Pathol,2013,182(1):132-141.
[3]Giacco F,Brownlee M.Oxidative stress and diabetic complications[J].Circ Res,2010,107(9):1058-1070.
[4]Joe Y,Zheng M,Kim HJ,et al.Salvianolic acid B exerts vasoprotective effects through the modulation of heme oxygenase-1 and arginase activities[J].J Pharmacol Exp Ther,2012,341(3):850-858.
[5]魏聪.糖尿病大血管病变的研究进展[J].上海交通大学学报:医学版,2010,30(10):1292-1295.
[6]Pradhan AD,Ridker PM.Do atherosclerosis and type 2diabetes share a common inflammatory basis?[J].Eur Heart J,2002,23(11):831-834.
[7]Mohammad Shahi M,Zakerzadeh M,Zakerkish M,et al.Effect of sesamin supplementation on glycemic status,inflammatory markers,and adiponectin levels in patients with type 2 diabetes mellitus[J].J Dietary Supplements,2017,14(1):65-75.
[8]Kolseth IB,Reine TM,Parker K,et al.Increased levels of inflammatory mediators and proinflammatory monocytes in patients with type I diabetes mellitus and nephropathy[J].J Diabetes Complications,2017,31(1):245-252.
[9]张安邦,高杰,李令根,等.相关炎症因子与动脉粥样硬化的关系[J].中国中西医结合外科杂志,2014,20(5):563-566.
[10]王晓晨,吉爱国.NF-κB信号通路与炎症反应[J].生理科学进展,2014,45(1):68-71.
[11]刘俊田.动脉粥样硬化发病的炎症机制的研究进展[J].西安交通大学学报:医学版,2015,36(2):141-152.
[12]郭丽婷,高志红,葛焕琦.2型糖尿病患者外周血micro RNA-155、细胞核因子-κB和可溶性细胞间黏附分子-1的表达及其与血管并发症的关系研究[J].中国糖尿病杂志,2017,25(3):213-217.
[13]刘江月.降糖调脂灵抑制核因子κB核转位对T2DM血管内皮的损伤作用[J].时珍国医国药,2015,26(3):567-570.
© 2004-2018 中国地质图书馆版权所有 京ICP备05064691号 京公网安备11010802017129号 地址：北京市海淀区学院路29号 邮编：100083 电话：办公室：(+86 10)66554848；文献借阅、咨询服务、科技查新：66554700 |