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  

Effect of salvianolic acid B on vasodilatory function,NF-κB activation and inflammatory cytokine expression in diabetic rats

作　　者：赵梦秋 任尤楠 陶善珺 吴元洁[3] 郑书国[2] 洪勇 ZHAO Meng-qiu;REN You-nan;TAO Shan-jun;WU Yuan-jie;ZHENG Shu-guo;HONG Yong(Department of Pharmacy, Anhui Health Vocational College, Chizhou 247099, China;Department of Pharmacology, Wannan Medical College, Wuhu 241002, China;Department of Basic Theory of Chinese Medicine, Anhui University of Chinese Medicine, Hefei 230038, China;Department of Anatomy, Anhui Health Vocational College, Chizhou 247099, China)

机构地区：[1]安徽卫生健康职业学院药学教研室,安徽池州247099 [2]皖南医学院药理学教研室,安徽芜湖241002 [3]安徽中医药大学中医基础理论教研室,安徽合肥230038 [4]安徽卫生健康职业学院解剖教研室,安徽池州247099

出　　处：《中国病理生理杂志》2018年第3期481-487,共7页Chinese Journal of Pathophysiology

基　　金：国家自然科学基金资助项目(No.81102626);安徽高校省级自然科学研究重点项目(No.KJ2015A192);安徽省教育厅省级示范实验实训中心--医学影像技术专业实验实训中心(No.2016SX2X012)

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 for4weeks,followed by a single intraperitoneal injection of streptozotocin(40mg/kg).The rats with random blood glucose level over16.7mmol/L were considered diabetic and randomly allocated to3groups,namely model group,low dose(80mg·kg-1·d-1)of salvianolic acid B group and high dose(160mg·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 for6weeks.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<0.05or 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<0.05or P<0.01).Salvianolic acid B markedly down-regulated NF-κB p65nuclear translocation and protein expression of ICAM-1and MCP-1in aorta tissues(P<0.05or 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 activa

关 键 词：丹酚酸B 糖尿病 血管舒张功能 炎症 氧化应激 

分 类 号：R587.1[医药卫生—内分泌] R285.5[医药卫生—内科学]