天香丹通过GRP78/NLRP3信号通路调控内质网应激抗动脉粥样硬化的作用机制研究  

The Anti-atherosclerosis Mechanism of Tianxiangdan by Regulating Endoplasmic Reticulum Stress Through GRP78/NLRP3 Signaling Pathway

作　　者：张夏夏 白银雪 吴丹丹 孙龙飞[2] 任珊 安冬青[2] ZHANG Xiaxia;BAI Yinxue;WU Dandan;SUN Longfei;REN Shan;AN Dongqing(Xinjiang Medical University Institute of TCM,Urumqi 830011,Xinjiang,China)

机构地区：[1]新疆医科大学中医学院,乌鲁木齐830011 [2]新疆医科大学附属中医医院,乌鲁木齐830000

出　　处：《中西医结合心脑血管病杂志》2024年第11期1955-1960,共6页Chinese Journal of Integrative Medicine on Cardio-Cerebrovascular Disease

基　　金：国家自然科学基金项目(No.8206150791);新疆维吾尔自治区重点实验室开放课题(No.2023D04052);新疆维吾尔自治区研究生创新项目(No.XJ2023G198);新疆维吾尔自治区重点实验室项目(No.2020D04006);新疆维吾尔自治区重大科技专项(No.2022A03019)。

摘　　要：目的:基于葡萄糖调节蛋白78(GRP78)/NOD样受体蛋白3(NLRP3)信号通路探讨天香丹通过调控内质网应激抗动脉粥样硬化的作用机制。方法:将雄性载脂蛋白E基因敲除(ApoE^(-/-))小鼠随机分为模型组、阿托伐他汀组、天香丹组,每组11只,给予高脂饲料诱导动脉粥样硬化模型;另取10只雄性C57BL/6J小鼠作为正常组。于造模10周后给予相应药物治疗,连续干预12周。采用苏木精-伊红(HE)染色观法察胸主动脉病理特点;酶联免疫吸附试验(ELISA)检测血清白细胞介素1β(IL-1β)、白细胞介素18(IL-18)、活性氧(ROS)含量;免疫组织化学法(IHC-P)检测胸主动脉中GRP78和NLRP3蛋白阳性表达水平。结果:各实验组存活6只。与模型组比较,阿托伐他汀组和天香丹组IL-1β、IL-18、ROS表达含量均降低(P<0.05或P<0.01);GRP78、NLRP3蛋白阳性表达均明显减少(P<0.05或P<0.01)。结论:天香丹能有效改善动脉粥样硬化性心血管疾病小鼠炎症反应,其作用机制可能与调控内质网应激GRP78/NLRP3信号通路抑制炎症小体活化、减轻动脉粥样硬化炎症损伤有关。Objective:Based on the glucose-regulatory protein 78(GRP78)/NOD-like receptor protein 3(NLRP3)signaling pathway to explore the anti-atherosclerosis mechanism of Tianxiangdan through regulation of endoplasmic reticulum stress.Methods:A total of 35 male apolipoprotein E gene knockout(ApoE^(-/-))mice were randomly divided into model group,atorvastatin group and Tianxiangdan group,with 6 mice in each group.Atherosclerosis model was induced by high fat diet.Another 10 male C57BL/6J mice were selected as the normal group.After 10 weeks of modeling,the corresponding drug treatment was given.The intervention lasted for 12 weeks.Hematoxylin-eosin(HE)staining was used to observe the pathological features of thoracic aorta.Serum interleukin-1β(IL-1β),interleukin-18(IL-18)and reactive oxygen species(ROS)were detected by enzyme-linked immunosorbent assay(ELISA).The positive expression levels of GRP78 and NLRP3 proteins in thoracic aorta were detected by immunohistochemistry(IHC-P).Results:Compared with model group,the expression levels of IL-1β,IL-18 and ROS in atorvastatin group and Tianxiangdan group decreased(P<0.05 or P<0.01),the positive expressions of GRP78 and NLRP3 decreased(P<0.05 or P<0.01).Conclusion:Tiangdan can effectively improve the inflammatory response of mice with atherosclerotic cardiovascular disease,and its mechanism may be related to the regulation of endoplasmic reticulum stress GRP78/NLRP3 signaling pathway to inhibit the activation of inflammasome and reduce the inflammatory damage of arteriosclerotic disease.

关 键 词：动脉粥样硬化 天香丹 内质网应激 葡萄糖调节蛋白78 NOD样受体蛋白3 实验研究 

分 类 号：R285.5[医药卫生—中药学]