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
Received date: 2024-02-08
Accepted date: 2024-04-15
Online published: 2024-08-27
Supported by
National Natural Science Foundation of China(8207140172)
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。
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
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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