通心痹合剂对动脉粥样硬化家兔血管内皮损伤及炎症反应的影响及其作用机制  

Effect and Mechanism of Tongxinbi Mixture on Vascular Endothelial Injury and Inflammatory Responses in Rabbits with Atherosclerosis

作　　者：汪满意 王道成[2] 马小东 薛刚[2] 屈长宏[2] 严士海[3] 朱萱萱[3] WANG Manyi;WANG Daocheng;MA Xiaodong;XUE Gang;QU Changhong;YAN Shihai;ZHU Xuanxuan(Medical College of Yangzhou University,Yangzhou 225009,China;Department of Cardiology,Nanjing University of Chinese Medicine Yangzhou Affiliated Hospital,Yangzhou 225009,China;Department of Pharmacology,Jiangsu Province Hospital of Chinese Medicine,Nanjing 210029,China)

机构地区：[1]扬州大学医学院,扬州225009 [2]南京中医药大学扬州附属医院心血管内科,扬州225009 [3]江苏省中医院药剂科,南京210029

出　　处：《世界中医药》2023年第17期2445-2451,共7页World Chinese Medicine

基　　金：江苏省重点研发计划项目(BE2020727);江苏省第三批老中医药专家学术传承指导项目(2019028)。

摘　　要：目的:基于核因子κB/NLRP3的炎症调控通路,探讨通心痹合剂对动脉粥样硬化家兔模型血管内皮损伤及炎症反应的影响及其作用机制。方法:采用高脂喂养加颈动脉球囊拉伤术建立动物模型,随机分为模型组、辛伐他汀组、通心痹合剂大剂量组、通心痹合剂中剂量组、通心痹合剂小剂量组,另选健康雄性家兔作为对照组。对照组饲喂正常饲料,其余组饲喂高脂饲料;辛伐他汀组给予辛伐他汀片(1.33 mg/kg)灌胃,通心痹合剂大剂量组、通心痹合剂中剂量组、通心痹合剂小剂量组分别给予9.87 g/kg、4.93 g/kg、2.47 g/kg通心痹合剂灌胃,对照组和模型组灌胃等体积生理盐水,连续给药8周。处死动物后检测血脂水平;应用酶联免疫吸附试验法检测血清一氧化氮、内皮肽;半定量法判断统计血管内皮生长因子、基质金属蛋白酶-9、核因子κB的阳性细胞计数;免疫组织化学法检测主动脉组织中血管内皮生长因子、基质金属蛋白酶-9、核因子κB蛋白的表达水平;蛋白质印迹法检测主动脉组织中核因子κB/NLRP3通路相关蛋白的表达水平。结果:与模型组比较,辛伐他汀组、通心痹合剂各剂量组家兔血清中的总胆固醇、三酰甘油、低密度脂蛋白胆固醇均明显改善(P<0.05,P<0.01);血管内皮生长因子、基质金属蛋白酶-9、核因子κB表达均明显降低(P<0.05,P<0.01);主动脉组织核苷酸结合寡聚化结构域样受体蛋白3(NLRP3)、凋亡相关斑样蛋白、原胱天蛋白酶-1、胱天蛋白酶-1表达水平均降低(均P<0.05,P<0.01)。结论:通心痹合剂可抑制核因子κB/NLRP3通路调控的炎症反应,保护血管内皮,从而缓解动脉粥样硬化的发展。Objective:To investigate the effect and mechanism of Tongxinbi Mixture on vascular endothelial injury and inflammatory responses in model rabbits with atherosclerosis based on the nuclear factorκB(NF-κB)/nucleotide-binding oligomerization domain-like receptor protein 3(NLRP3)inflammatory regulation pathway.Methods:The atherosclerosis model was induced by a high-fat diet and carotid artery balloon injury.The model rabbits were randomly divided into a model group,a simvastatin group,and high-,medium-,and low-dose Tongxinbi Mixture groups.Healthy male rabbits were selected and assigned to the control group.The rabbits in the control group were fed a normal diet,while those in the other groups were fed a high-fat diet.The simvastatin group received simvastatin tablets(1.33 mg/kg)by gavage,and the Tongxinbi Mixture groups received Tongxinbi Mixture at doses of 9.87 g/kg,4.93 g/kg,and 2.47 g/kg,respectively.The control group and the model group were given an equivalent volume of saline.Treatment was carried out continuously for 8 weeks.Blood lipid levels were measured after the animals were sacrificed.Enzyme-linked immunosorbent assay(ELISA)was used to detect serum nitric oxide and endothelin levels.Semi-quantitative method was used to determine the positive cell counts of vascular endothelial growth factor(VEGF),matrix metalloproteinase-9(MMP-9),and NF-κB.Immunohistochemistry was used to assess the protein expression levels of VEGF,MMP-9,and NF-κB in aortic tissue.Western blot was used to measure the expression levels of NF-κB/NLRP3 pathway-related proteins in aortic tissue.Results:Compared with the model group,the simvastatin group and the Tongxinbi Mixture groups showed significant improvements in serum total cholesterol,triglyceride,and low-density lipoprotein cholesterol(P<0.05,P<0.01),decreased expression of VEGF,MMP-9,and NF-κB(P<0.05,P<0.01),and reduced expression levels of NLRP3,apoptosis-associated speck-like protein,procaspase-1,and caspase-1(P<0.05,P<0.01).Conclusion:Tongxinbi Mixture can inhibit infl

关 键 词：通心痹合剂 动脉粥样硬化 家兔 核因子κB/NLRP3通路 血管内皮生长因子 基质金属蛋白酶-9 血管内皮损伤 炎症反应 

分 类 号：R289.5[医药卫生—方剂学]