论著 · 基础研究

番泻苷A对2型糖尿病小鼠动脉粥样硬化斑块形成及5-羟色胺信号分子表达的影响

  • 刘美志 ,
  • 王子杨 ,
  • 姜雅宁 ,
  • 弥萌 ,
  • 孙永宁
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  • 1.上海中医药大学附属市中医医院心病科,上海 200071
    2.陕西中医药大学第一临床医学院,西安 712046
刘美志(1994—),女,博士生;电子信箱:Mary53194@126.com
孙永宁,电子信箱:ynsun2002@126.com

收稿日期: 2024-02-08

  录用日期: 2024-04-15

  网络出版日期: 2024-08-27

基金资助

国家自然科学基金(8207140172)

Effects of sennoside A on atherosclerotic plaque formation and expression of 5-hydroxytryptamine signal moleculars in mice with diabetes mellitus type 2

  • Meizhi LIU ,
  • Ziyang WANG ,
  • Yaning JIANG ,
  • Meng MI ,
  • Yongning SUN
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  • 1.Department of Cardiology, Shanghai Municipal Hospital of Traditional Chinese Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai 200071, China
    2.The First Clinical Medical College, Shaanxi University of Chinese Medicine, Xi'an 712046, China
SUN Yongning, E-mail: ynsun2002@126.com.

Received date: 2024-02-08

  Accepted date: 2024-04-15

  Online published: 2024-08-27

Supported by

National Natural Science Foundation of China(8207140172)

摘要

目的·研究番泻苷A(sennoside A,SA)对2型糖尿病(diabetes mellitus type 2,T2DM)小鼠动脉粥样硬化斑块形成和5-羟色胺(5-hydroxytryptamine,5-HT)及其受体表达的影响。方法·将载脂蛋白E基因敲除小鼠12只随机分为模型组(model组)和治疗组(model+SA组),每组6只,同遗传背景C57BL/6J小鼠6只作为对照组(control组)。Control组普通饲养,model组和model+SA组在高脂饲养基础上每日给予腹腔注射30 mg/kg链脲佐菌素(streptozotocin,STZ)建立T2DM模型。Model+SA组每日给予SA(45 mg/kg)灌胃干预8周,control组和model组给予等体积双蒸水灌胃。比较造模及治疗前后小鼠体质量、空腹血糖和餐后2 h血糖情况,采用油红O染色和苏木精-伊红染色(hematoxylin-eosin staining,H-E染色)观察小鼠主动脉斑块面积,并用ELISA试剂盒测定小鼠血清和胸主动脉中5-HT水平,采用蛋白质印迹法(Western blotting)检测小鼠胸主动脉中5-羟色胺2B受体(5-hydroxytryptamine receptor 2B,HTR2B)和5-羟色胺转运蛋白(serotonin transporter,SERT)的表达情况。结果·与control组相比,model组小鼠体质量、空腹血糖和餐后2 h血糖均升高,糖代谢紊乱;主动脉斑块形成,胸主动脉中HTR2B、SERT蛋白表达升高;胸主动脉5-HT浓度降低,血清5-HT浓度升高(均P<0.05)。给予SA治疗后,与model组相比,model+SA组小鼠体质量下降,空腹血糖和餐后2 h血糖水平明显改善;主动脉斑块面积减少,胸主动脉HTR2B、SERT蛋白表达显著降低;胸主动脉5-HT浓度升高,血清5-HT浓度降低(均P<0.05)。结论·SA可减少T2DM小鼠动脉粥样硬化斑块面积,其作用可能与降低血糖、抑制5-HT及其受体表达有关。

本文引用格式

刘美志 , 王子杨 , 姜雅宁 , 弥萌 , 孙永宁 . 番泻苷A对2型糖尿病小鼠动脉粥样硬化斑块形成及5-羟色胺信号分子表达的影响[J]. 上海交通大学学报(医学版), 2024 , 44(8) : 991 -998 . DOI: 10.3969/j.issn.1674-8115.2024.08.008

Abstract

Objective ·To investigate the effects of sennoside A (SA) on the formation of atherosclerotic plaque and the expression of 5-hydroxytryptamine (5-HT) and its receptor in mice with diabetes mellitus type 2 (T2DM). Methods ·Twelve mice with knocked-out apolipoprotein E gene were randomly divided into two groups, namely the model group and the model+SA group, with six mice in each group. Six C57BL/6J mice with the same genetic background were used as the control group. The control group was fed with normal diet, and the model group and the model+SA group were given intraperitoneal injection of streptozotocin (30 mg/kg) daily on the basis of high-fat diet to establish a model of T2DM. The model+SA group was given SA daily by gavage for 8 weeks, and the control group and the model group were given equal volume of distillation-distillation H2O by gavage. The body weight, fasting blood glucose (FBG) and 2-h postprandial blood glucose of mice were compared before and after modeling and treatment. The area of aortic plaque was observed by oil red O staining and hematoxylin-eosin (H-E) staining, and the level of 5-HT in serum and thoracic aorta was measured by ELISA kit. Western blotting was used to detect the expression of 5-hydroxytryptamine receptor 2B (HTR2B) and serotonin transporter (SERT) in thoracic aorta of mice. Results ·Compared with the control group, the body weight, FBG and 2-h postprandial blood glucose in the model group increased, and glucose metabolism was disordered. The expression of HTR2B and SERT protein in thoracic aorta increased, while the concentration of 5-HT in thoracic aorta decreased. The serum 5-HT concentration increased (all P<0.05). After treatment with SA, compared with the model group, the body weight of the model+SA group decreased, and FBG and 2-h postprandial blood glucose were significantly improved. The area of aortic plaque and the expression of HTR2B and SERT protein in thoracic aorta significantly decreased, while the concentration of 5-HT increased. The serum 5-HT concentration decreased (all P<0.05). Conclusion ·SA can reduce atherosclerotic plaque area in T2DM mice, which may be related to lowering blood glucose and inhibiting the expression of 5-HT and its receptor.

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