海参皂苷调节SIRT1/NF-κB信号通路对糖尿病大鼠血管炎症的影响  

Effect of Sea Cucumber Saponin on Vascular Inflammation in Diabetic Rats by Regulation of SIRT1/NF-κB Signaling Pathway

作　　者：杨铮[1] 张亮[1] 牛海光 张宏光[1] 索青霞 YANG Zheng;ZHANG Liang;NIU Haiguang;ZHANG Hongguang;SUO Qingxia(Baoding Second Hospital,Baoding 071000,Hebei,China;Baoding Maternal and Child Health Hospital,Baoding 071000,Hebei,China)

机构地区：[1]保定市第二医院,河北保定071000 [2]保定市妇幼保健院,河北保定071000

出　　处：《中西医结合心脑血管病杂志》2024年第21期3913-3918,共6页Chinese Journal of Integrative Medicine on Cardio-Cerebrovascular Disease

基　　金：保定市科学技术局2019年科技项目(No.1951ZF009)。

摘　　要：目的:探讨海参皂苷(SSC)对糖尿病大鼠血管炎症的影响及潜在机制。方法:SD大鼠采用高糖高脂饮食和链脲佐菌素(STZ)腹腔注射构建糖尿病模型。实验分为对照(Control)组、模型(model)组、二甲双胍组(600 mg/kg)、SSC组(30 mg/kg)和SSC+沉默信息调节因子1(SIRT1)抑制剂EX-527组(SSC 30 mg/kg+EX-5275 mg/kg)。给予相应的药物干预4周后,检测各组大鼠空腹血糖(FBG)和空腹胰岛素(FINS)水平,计算胰岛素抵抗指数(HOMA-IR);酶联免疫吸附法(ELISA)检测血清血管细胞黏附分子-1(VCAM-1)、单核细胞趋化因子-1(MCP-1)、肿瘤坏死因子-α(TNF-α)和白细胞介素-1β(IL-1β)水平;苏木精-伊红(HE)染色观察主动脉病理学变化;蛋白免疫印迹法(Western Blot)检测主动脉SIRT1/核因子-κB(NF-κB)通路相关蛋白的表达。结果:与Control组比较,model组大鼠FBG、FINS、HOMA-IR、血清VCAM-1、MCP-1、TNF-α、IL-1β水平、胞核NF-κB p65蛋白水平升高(P<0.05),体质量、主动脉SIRT1、核因子κB抑制蛋白α(IκBα)蛋白水平降低(P<0.05);与model组比较,SSC组和二甲双胍组大鼠FBG、FINS、HOMA-IR、血清VCAM-1、MCP-1、TNF-α、IL-1β水平、胞核NF-κB p65的蛋白水平降低(P<0.05),体质量、主动脉SIRT1、IκBα蛋白水平升高(P<0.05);与SSC组比较,SSC+EX-527组大鼠FBG、FINS、HOMA-IR、血清VCAM-1、MCP-1、TNF-α、IL-1β水平、胞核NF-κB p65蛋白水平升高(P<0.05),体质量、主动脉SIRT1、IκBα蛋白水平降低(P<0.05)。结论:SSC可减轻糖尿病大鼠血管炎症,其作用机制可能与上调SIRT1表达,抑制NF-κB的活化有关。Objective:To investigate the effect of sea cucumber saponin(SSC)on vascular inflammation in diabetic rats and its potential mechanism.Methods:SD rats were treated with high-sugar and high-fat diet,and streptozotocin(STZ)intraperitoneal injection to construct diabetes model.The rats were divided into Control group,model group,metformin group(600 mg/kg),SSC group(30 mg/kg),and SSC+silencing information regulatory factor 1(SIRT1)inhibitor EX-527 group(SSC 30 mg/kg+EX-5275 mg/kg).After 4 weeks of drug intervention,fasting blood glucose(FBG)and fasting insulin(FINS)levels were detected,and insulin resistance index(HOMA-IR)was calculated.Serum vascular cell adhesion molecule-1(VCAM-1),monocyte chemokine-1(MCP-1),tumor necrosis factorα(TNF-α),and interleukin-1β(IL-1β)levels were detected by enzyme-linked immunosorbent assay(ELISA).Hematoxylin-eosin(HE)staining was used to observe the pathological changes of aorta.The expression of SIRT1/nuclear factor-κB(NF-κB)pathway-related proteins in aorta was detected by Western Blot.Results:Compared with Control group,the levels of FBG,FINS,HOMA-IR,serum VCAM-1,MCP-1,TNF-α,IL-1β,and nuclear NF-κB p65 protein in model group increased(P<0.05),the levels of body mass,aorta SIRT1 and nuclear factorκB inhibitory proteinα(IκBα)decreased(P<0.05).Compared with model group,the levels of FBG,FINS,HOMA-IR,serum VCAM-1,MCP-1,TNF-α,IL-1β,and nuclear NF-κB p65 in SSC group and metformin group decreased(P<0.05),the levels of body mass,aorta SIRT1 and IκBαprotein increased(P<0.05).Compared with SSC group,the levels of FBG,FINS,HOMA-IR,serum VCAM-1,MCP-1,TNF-α,IL-1β,and nuclear NF-κB p65 protein in SSC+EX-527 group increased(P<0.05),the levels of body mass,aortic SIRT1 and IκBαprotein decreased(P<0.05).Conclusion:SSC can reduce vascular inflammation in diabetic rats,and its mechanism may be related to up-regulation of SIRT1 expression and inhibition of NF-κB activation.

关 键 词：糖尿病 血管炎症 海参皂苷 沉默信息调节因子1 核因子-ΚB 实验研究 

分 类 号：R285.5[医药卫生—中药学]