基于NOD1/RIP2/NF-κB信号通路探讨丁酸钠对动脉粥样硬化大鼠斑块形成和炎症反应的影响  

Effects of sodium butyrate on plaque formation and inflammatory responses in atherosclerotic rats through the NOD1/RIP2/NF-κB signaling pathway

作　　者：聂俊丽 谈宝珍 余稳 侯亮 NIE Jun-li;TAN Bao-zhen;YU Wen;HOU Liang(Department of Health Medicine Science,General Hospital of the Yangtze River Shipping,Wuhan 430000,China;Department of Cardiovascular Medicine,General Hospital of the Yangtze River Shipping,Wuhan 430000,China)

机构地区：[1]长江航运总医院健康医学科,武汉430000 [2]长江航运总医院心血管内科,武汉430000

出　　处：《现代免疫学》2024年第5期369-374,381,共7页Current Immunology

基　　金：武汉市卫生健康委计划资助项目(WX20Q10)。

摘　　要：基于核苷酸结合寡聚域样受体1(nucleotide-binding oligodomain-like receptor 1,NOD1)/受体相互作用蛋白2(receptor-interacting protein 2,RIP2)/NF-κB信号通路探讨丁酸钠(sodium butyrate,NaB)对动脉粥样硬化(atherosclerosis,AS)大鼠斑块形成和炎症反应的影响。给予41只大鼠球囊受损结合高脂饮食构建AS模型,共建模成功36只。将36只模型大鼠分为模型组、 NaB组和NaB+NOD1激动剂二氨基庚二酸(γ-D-glu-mesodiaminopimelic acid,iE-DAP)组,每组12只。另假手术组12只大鼠仅分离左侧颈总动脉后缝合。模型组、 NaB组和NaB+iE-DAP组给予高脂饲料饲养,假手术组给予基础饲料饲养;NaB组灌胃10 g/(kg·d)NaB,NaB+iE-DAP组灌胃10 g/(kg·d)NaB的同时腹腔注射1 mL/(只·周)iE-DAP;模型组、假手术组灌胃和腹腔注射等量的生理盐水;以上处理均持续12周。H-E染色观察主动脉形态;ELISA检测各组大鼠血清甘油三酯(triglyceride,TG)、总胆固醇(total cholesterol,TC)、低密度脂蛋白胆固醇(low-density lipoprotein cholesterol,LDL-C)、高密度脂蛋白胆固醇(high-density lipoprotein cholesterol,HDL-C)、氧化型低密度脂蛋白(oxidized low-density lipoprotein,ox-LDL)、单核细胞趋化蛋白1(monocyte chemoattractant protein 1,MCP-1)、超敏C反应蛋白(high-sensitivity C-reactive protein,hs-CRP)、 TNF-α和IL-1的含量;免疫组化染色评估主动脉中细胞间黏附分子1(intercellular cell adhesion molecule 1,ICAM-1)蛋白表达情况;Western blotting检测主动脉组织中NOD1、 RIP2和NF-κB蛋白表达情况。结果显示,模型组主动脉受损严重,而NaB组主动脉损伤表现减轻,NaB+iE-DAP组表现有所加重。与假手术组相比,模型组血清TG、 TC、 LDL-C、 ox-LDL、 MCP-1、 hs-CRP、 TNF-α和IL-1含量,主动脉组织ICAM-1阳性率,NOD1、 RIP2及细胞核NF-κB蛋白表达水平显著升高(均P<0.05),HDL-C含量及细胞质NF-κB蛋白表达水平显著降低(均P<0.05);与模型组相比,NaB组血清TG、 TC、 LDL-C、 This study aimed to investigate the effects of sodium butyrate (NaB) on plaque formation and inflammatory responses in atherosclerotic (AS) rats through the nucleotide-binding oligodomain-like receptor 1 (NOD1)/receptor-interacting protein 2 (RIP2)/NF-κB signaling pathway. AS model on 41 rats was given by combination of balloon injury and high-fat diet (HFD), and a total of thirty-six rats were successfully modeled. Thirty-six AS rats were divided into model group, NaB group, and NaB+NOD1 agonist γ-D-glu-mesodiaminopimelic acid (iE-DAP) group, with 12 rats in each group. The sham operation group rats were only given exposure of left common carotid artery and successive suture. The model group, NaB group and NaB+iE-DAP group were cultured with HFD while the sham operation group was cultured routinely. NaB group was gavaged with 10 g/(kg·d) NaB, NaB+iE-DAP group was gavaged with 10 g/(kg·d) NaB and peritoneally injected with 1 mL/(each·week) iE-DAP;Model group and sham operation group were gavaged and peritoneally injected with the same volume saline;All the above treatments lasted for twelve weeks. Aorta histomorphology was evaluated by H-E staining. The levels of serum TG, TC, LDL-C, HDL-C, ox-LDL, MCP-1, hs-CRP, TNF-α, and IL-1 were measured by ELISA. Immunohistochemistry was performed to measure ICAM-1 protein expression in the aorta and western blotting was used to measure the protein levels of NOD1, RIP2 and NF-κB in the aorta. The results showed that the aorta lesion was severe in the model group, alleviated in the NaB group and aggravated in the NaB+iE-DAP group. Compared to those of the sham operation group, the serum levels of TG, TC, LDL-C, ox-LDL, MCP-1, hs-CRP, TNF-α,and IL-1, the positive rate of aortic ICAM-1, the expression levels of NOD1, RIP2 and nuclear NF-κB in the model group were significantly increased (all with P<0.05), while the levels of HDL-C and cytoplasmic NF-κB protein were significantly decreased (both P<0.05). In the NaB group, all these indexes showed changes in the revers

关 键 词：丁酸钠 动脉粥样硬化 核苷酸结合寡聚域样受体1/受体相互作用蛋白2/核因子κB信号通路 斑块形成 炎症反应 

分 类 号：R392.12[医药卫生—免疫学]