摘要
目的观察黄连解毒汤对动脉粥样硬化(AS)大鼠血管内皮损伤及活性氧(ROS)/核苷酸结合寡聚化结构域样受体蛋白3(NLRP3)通路的影响。方法建立AS大鼠模型,将其分为对照组、模型组、黄连解毒汤低、中、高剂量组、黄连解毒汤高剂量+ROS激活剂氧化三甲胺(TMAO)组;全自动生化分析仪检测大鼠血清总胆固醇(TC)、三酰甘油(TG)、低密度脂蛋白胆固醇(LDL-C)、高密度脂蛋白胆固醇(HDLC)、一氧化氮(NO)水平;ELISA检测肿瘤坏死因子(TNF-)、白细胞介素-6(IL-6)、白细胞介素-1(IL-1)、超氧化物歧化酶(SOD)、丙二醛(MDA)、活性氧(ROS)、内皮素-1(ET-1)水平;HE染色检测大鼠胸主动脉病理形态学变化;免疫印迹法检测NLRP3、半胱天冬酶-1(Caspase-1)的表达水平。结果与对照组比较,模型组大鼠主动脉血管内皮损伤严重,血管血管壁和内膜增厚,大量脂质斑块沉积,TC、TG、LDL-C、MDA、TNF-、IL-6、IL-1、ET-1、ROS、NLRP3、Caspase-1表达升高,HDL-C、SOD、NO水平降低(P<0.05);与模型组比较,黄连解毒汤低、中、高剂量组大鼠脂质斑块沉积逐渐减少,主动脉血管内皮损伤及增厚逐渐减轻,TC、TG、LDL-C、MDA、TNF-、IL-6、IL-1、ET-1、ROS、NLRP3、Caspase-1表达依次降低,HDL-C、SOD、NO水平依次升高(P<0.05);与黄连解毒汤高剂量组比较,黄连解毒汤高剂量+TMAO组大鼠主动脉血管内皮增厚、损伤加重,脂质斑块沉积增多,TC、TG、LDL-C、MDA、TNF-、IL-6、IL-1、ET-1、ROS、NLRP3、Caspase-1表达升高,HDL-C、SOD、NO水平降低(P<0.05)。结论黄连解毒汤通过抑制ROS/NLRP3通路保护AS大鼠血管内皮损伤。
Objective To investigate the effects of Huanglian Jiedu Decoction on vascular endothelial injury and reactive oxygen species(ROS)/nucleotide-binding oligomeric domain-like receptor protein 3(NLRP3)pathway in atherosclerosis(AS)rats.Methods An AS rat model were established and the experimental rats were divided into control group,model group,low,medium,high dose Huanglian Jiedu Decoction groups,and high-dose Huanglian Jiedu Decoction+ROS activator trimethylamine oxide(TMAO)group;fully automated biochemical analyzer was applied to detect the levels of total cholesterol(TC),triacylglycerol(TG),low-density lipoprotein cholesterol(LDL-C),high-density lipoprotein cholesterol(HDL-C),and nitric oxide(NO)in serum;ELISA was applied to detect levels of tumor necrosis factor-(TNF-),interleukin-6(IL-6),IL-1,superoxide dismutase(SOD),malondialdehyde(MDA),reactive oxygen species(ROS),and endothelin-1(ET-1);HE staining was applied to detect pathological and morphological changes in the thoracic aorta of rats;Western Blot was applied to detect the expression levels of NLRP3 and Caspase-1.Results Compared with control group,model group had severe endothelial damage to the aorta,thickening of the vascular wall and intima,and a large number of lipid plaques deposition;TC,TG,LDL-C,MDA,TNF-,IL-6,IL-1,ET-1 levels,ROS,NLRP3,and Caspase-1 expression were significantly increased;HDL-C,SOD,and NO levels were obviously decreased(P<0.05);compared with model group,lipid plaques deposition in low,medium,and high dose Huanglian Jiedu Decoction groups gradually decreased,and the damage and thickening of the aortic endothelial cells gradually decreased;TC,TG,LDL-C,MDA,TNF-,IL-6,IL-1,ET-1 levels,ROS,NLRP3,and Caspase-1 expression were significantly reduced in sequence;HDL-C,SOD,and NO levels were significantly decreased in sequence(P<0.05);compared with high dose Huanglian Jiedu Decoction group,high-dose Huanglian Jiedu Decoction+trimethylamine oxide group showed increased endothelial thickening,damage to the aorta,and deposition of lipid plaques;
作者
夏铭蔚
左强
冉永玲
张军
XIA Ming-wei;ZUO Qiang;RAN Yong-ing;ZHANG Jun(First Affiliated Hospital of Anhui University of Chinese Medicine,Hefei 230031)
出处
《湖北中医药大学学报》
2024年第3期14-18,共5页
Journal of Hubei University of Chinese Medicine
基金
安徽省高等学校科学研究项目(项目编号:2022AH050473)。
