[1]康家润,马立人,豆星月,等.基于环磷酸鸟苷-腺苷酸合成酶-干扰素基因刺激因子信号通路探讨桦木酸对糖尿病动脉粥样硬化大鼠主动脉内皮功能的调控作用[J].陕西医学杂志,2026,(1):22-28.[doi:DOI:10.3969/j.issn.1000-7377.2026.01.004]
　KANG Jiarun,MA Liren,DOU Xingyue,et al.Exploration of the regulatory role of betulinic acid on aortic endothelial function in rats with diabetic atherosclerosis via the cGAS-STING signaling pathway[J].,2026,(1):22-28.[doi:DOI:10.3969/j.issn.1000-7377.2026.01.004]
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基于环磷酸鸟苷-腺苷酸合成酶-干扰素基因刺激因子信号通路探讨桦木酸对糖尿病动脉粥样硬化大鼠主动脉内皮功能的调控作用

《陕西医学杂志》[ISSN:1000-7377/CN:61-1281/TN]

卷:
期数:
2026年1期
页码:
22-28
栏目:
基础研究
出版日期:
2026-01-05

文章信息/Info

Title:
Exploration of the regulatory role of betulinic acid on aortic endothelial function in rats with diabetic atherosclerosis via the cGAS-STING signaling pathway
作者:
康家润1; 马立人2; 豆星月1; 梁荟玲1
（1.河南中医药大学第一临床医学院,河南 郑州450000；2.平顶山市中医医院周围血管科，河南 平顶山 467000）
Author(s):
KANG Jiarun1; MA Liren2; DOU Xingyue1; LIANG Huiling1
(1.The First Clinical Medical College of He’nan University of Traditional Chinese Medicine,Zhengzhou 450000,China；2.Department of Peripheral Vascular,Pingdingshan Traditional Chinese Medicine Hospital,Pingdingshan 467000,China）
关键词:
桦木酸; 环磷酸鸟苷-腺苷酸合成酶; 干扰素基因刺激因子; 炎症; 内皮功能; 糖尿病动脉粥样硬化
Keywords:
Betulinic acid; cGAS; STING; Inflammatory; Endothelial function; Diabetic atherosclerosis
分类号:
R 587.1
DOI:
DOI:10.3969/j.issn.1000-7377.2026.01.004
文献标志码:
A
摘要:
目的：基于环磷酸鸟苷-腺苷酸合成酶（cGAS）-干扰素基因刺激因子（STING）信号通路探讨桦木酸对糖尿病动脉粥样硬化大鼠主动脉内皮功能的影响并初步探讨其可能的作用机制。方法：将90只4周龄的大鼠随机分为对照组、模型组、桦木酸低剂量组（20 mg/kg）、桦木酸高剂量组（100 mg/kg）、桦木酸高剂量+环鸟苷酸-腺苷酸（cGAMP）组（100 mg/kg+200 μg），每组18只。采用一次性腹腔注射链脲佐菌素（STZ）联合高糖高脂饲养构建糖尿病动脉粥样硬化大鼠模型。血糖仪检测大鼠空腹血糖（FBG）水平，酶联免疫吸附（ELISA）检测大鼠血清中空腹胰岛素（FINS）、胰岛素抵抗指数（HOMA-IR）、一氧化氮合酶（eNOS）、一氧化氮（NO）、内皮素-1（ET-1）、血管性血友病因子（vWF）、白细胞介素-6（IL-6）、肿瘤坏死因子-α（TNF-α）、IL-1β水平，检测血清中总胆固醇（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（HDL-C）水平，苏木精-伊红（HE）染色用于观察大鼠主动脉组织形态变化，生物信号采集分析器检测血管张力，蛋白免疫印记（WB）检测主动脉组织中的蛋白水平。结果：与对照组比较，模型组中大鼠主动脉组织损伤程度加重，斑块面积、FBG、FINS、HOMA-IR、TC、TG、LDL-C、ET-1、vWF、IL-6、IL-1β、TNF-α水平、cGAS、p-STING/STING的蛋白表达水平升高（均P<0.05），HDL-C、血管内皮最大舒张率、eNOS、NO水平降低（均P<0.05）。与模型组比较，桦木酸低剂量和高剂量组大鼠主动脉组织损伤程度减轻，斑块面积、FBG、FINS、HOMA-IR、TC、TG、LDL-C、ET-1、vWF、IL-6、IL-1β、TNF-α水平、cGAS、p-STING/STING的蛋白表达水平降低（均P<0.05），HDL-C、血管内皮最大舒张率、eNOS、NO水平升高（均P<0.05）。而cGAMP能逆转桦木酸对糖尿病动脉硬化大鼠的治疗作用。结论：桦木酸可能通过抑制cGAS-STING信号通路，调节糖脂代谢和炎症因子分泌，改善糖尿病动脉硬化大鼠主动脉内皮细胞的功能。
Abstract:
Objective:To investigate the effect of betulinic acid (BA) on aortic endothelial function in rats with diabetic atherosclerosis (DAS) and explore its potential mechanism based on the cyclic guanosine monophosphate-adenosine monophosphate synthase (cGAS)-stimulator of interferon genes (STING) signaling pathway.Methods：Ninety 4-week-old rats were randomly divided into a control group,a model group,a low-dose betulinic acid group (20 mg/kg),a high-dose betulinic acid group (100 mg/kg),and a high-dose betulinic acid+cGAMP group (100 mg/kg+200 μg),with 18 rats in each group.The DAS rat model was established by a single intraperitoneal injection of streptozotocin (STZ) combined with high-sugar and high-fat feeding.Fasting blood glucose (FBG) levels were measured using a blood glucose meter.ELISA was used to detect the serum levels of fasting insulin (FINS),homeostasis model assessment of insulin resistance (HOMA-IR),endothelial nitric oxide synthase (eNOS),nitric oxide (NO),endothelin-1 (ET-1),von Willebrand factor (vWF),interleukin-6 (IL-6),tumor necrosis factor-α (TNF-α),and interleukin-1β(IL-1β).Additionally,serum levels of total cholesterol (TC),triglycerides (TG),low-density lipoprotein cholesterol (LDL-C),and high-density lipoprotein cholesterol (HDL-C) were determined.Hematoxylin-eosin (HE) staining was performed to observe the morphological changes of rat aortic tissue.Vascular tension was measured using a biological signal acquisition analyzer.Western blot (WB) was used to detect the protein expression levels of in rat aortic tissue.Results:Compared with the control group,the model group showed aggravated aortic tissue damage,increased levels of plaque area,FBG,FINS,HOMA-IR,TC,TG,LDL-C,ET-1,vWF,IL-6,IL-1β,and TNF-α,as well as elevated protein expression levels of cGAS and the p-STING/STING ratio (all P<0.05).in contrast,the levels of HDL-C,maximum vascular endothelial relaxation rate,eNOS,and NO were decreased (all P<0.05).Compared with the model group,the low-dose and high-dose BA groups exhibited alleviated aortic tissue damage,reduced levels of plaque area,FBG,FINS,HOMA-IR,TC,TG,LDL-C,ET-1,vWF,IL-6,IL-1β,and TNF-α,and downregulated protein expression levels of cGAS and the p-STING/STING ratio v.meanwhile,the levels of HDL-C,maximum vascular endothelial relaxation rate,eNOS,and NO were increased (all P<0.05).However,cGAMP could reverse the therapeutic effect of BA on rats with diabetic atherosclerosis.Conclusion:Betulinic acid may improve the function of aortic endothelial cells in diabetic arteriosclerotic rats by inhibiting the cGAS-STING signaling pathway,regulating glucose and lipid metabolism,and reducing the secretion of inflammatory factors.

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备注/Memo

备注/Memo:
河南省中医药科学研究专项课题（2022ZY1189）
更新日期/Last Update: 2026-01-05