天津医药

天津医药 ›› 2020, Vol. 48 ›› Issue (3): 182-186.doi: 10.11958/20193022

• 实验研究 • 上一篇    下一篇

阿魏酸对2型糖尿病小鼠心肌损伤的影响

王一春，王丽娟，刘萍   

  1. 1宁夏医科大学总医院内分泌科（邮编750004）；2宁夏银川市第二人民医院心血管内科
  • 收稿日期:2019-10-12 修回日期:2019-12-29 出版日期:2020-03-15 发布日期:2020-04-11
  • 通讯作者: 刘萍 E-mail:1055296971@qq.com

Effects of ferulic acid on myocardial injury in type 2 diabetic mice

WANG Yi-chun,WANG Li-juan,LIU Ping   

  1. 1 Department of Endocrinology, the General Hospital of Ningxia Medical University, Yinchuan 750004, China; 2 Cardiovascular Department, Yinchuan Second People’s Hospital
  • Received:2019-10-12 Revised:2019-12-29 Published:2020-03-15 Online:2020-04-11

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摘要： 目的 探讨阿魏酸对 2型糖尿病 db/db小鼠心肌损伤的保护作用及其作用机制。方法 将适应性饲养后筛选出的 20只 2型糖尿病 db/db小鼠随机均分为模型组和阿魏酸组，另随机抽取 10只正常 db/m小鼠作为对照组。对照组和模型组灌胃蒸馏水，阿魏酸组灌胃阿魏酸（30 mg/kg），每天灌胃1次，连续给药8周后处死，取血清检测血糖（BG）、肌酸激酶（CK）、肌酸激酶同工酶（CK-MB）和糖基化终末代谢产物（AGEs）含量。HE和 Masson染色观察心脏组织形态学改变；实时荧光定量PCR（Q-PCR）检测Toll样受体4（TLR-4）、核转录因子-ĸB（NF-ĸB）、核苷酸结合寡聚化结构域样受体3（NALP3）mRNA表达情况；免疫组化染色和Western blot法检测TLR-4、NF-ĸB、NALP3蛋白表达情况。结果 模型组小鼠体质量、心脏质量和心脏质量指数较对照组明显增高，阿魏酸干预后，体质量、心脏质量和心脏质量指数较模型组明显降低（均P＜0.05），模型组小鼠心肌细胞肿胀肥大，可见明显纤维增生，阿魏酸干预后心肌细胞肿胀情况和纤维增生情况明显减轻；模型组血清BG、CK、CK-MB、AGEs表达水平明显升高，阿魏酸干预后，血清BG、CK、CK-MB、AGEs表达水平较模型组明显降低（均 P＜0.05）；模型组 TLR-4、NF-ĸB、NALP3 mRNA和蛋白表达水平均明显高于对照组，阿魏酸干预后 TLR-4、NF-ĸB、NALP3 mRNA 和蛋白表达水平明显降低（均 P＜0.05）。结 论 阿魏酸具有改善2型糖尿病小鼠血糖水平，减轻心肌细胞损伤及心肌纤维化的作用，其机制可能与抑制TLR-4/NF-ĸB信号通路，抑制炎症反应有关。

关键词: 阿魏酸, 糖尿病, 2型, 糖尿病心肌病, Toll样受体4, NF-κB, 核苷酸结合寡聚化结构域样受体3

Abstract: Objective To investigate the protective effect and its mechanism of ferulic acid on myocardial injury in type 2 diabetic db/db mice. Methods Twenty db/ db mice with type 2 diabetes were randomly divided into model group and ferulic acid group, and 10 normal db/ m mice were randomly selected as control group. The control group and model group were intragastrically given distilled water, and ferulic acid group was given ferulic acid (30 mg/kg) once a day. After 8 weeks of continuous administration, the serum levels of glucose (BG), creatine kinase (CK), creatine kinase isoenzyme (CKMB) and advanced glycation end products (AGEs) were measured. The morphological changes of myocardial tissues were observed by HE and Masson's staining. The mRNA expressions of TLR-4, NF-ĸB and NALP3 were determined by Q-PCR.Immunocytochemistry and Western blot assay were used to detect the expressions of TLR-4, NF-ĸB and NALP3 proteins.Results The body mass, heart mass and cardiac mass index were significantly higher in the model group than those in the control group. After ferulic acid intervention, the body mass, heart mass and heart mass index were significantly decreased compared with those of the model group (P＜0.05). In the model group, the myocardial cells were swollen and hypertrophy, and obvious fiber proliferation was found. After the intervention with ferulic acid, the swelling of cardiomyocytes and the proliferation of fibers were significantly alleviated. The expression levels of serum BG, CK, CK-MB and AGEs were significantly higher in the model group than those in the normal group. After treatment with ferulic acid, the serum levels of BG, CK, CK-MB and AGEs were decreased compared with those of model group (P＜0.05). The mRNA and protein expression levels of TLR-4, NF-ĸB and NALP3 were significantly higher in the model group than those in the control group.After ferulic acid intervention, the mRNA and protein expression levels of TLR-4, NF-ĸB and NALP3 were significantly decreased (P＜0.05). Conclusion Ferulic acid can improve blood glucose level and reduce myocardial cell injury and myocardial fibrosis in type 2 diabetic mice, which may be related to the inhibition of TLR-4/NF- ĸB signal pathway and inflammation.

Key words: FERULIC ACID, diabetes mellitus, type 2, diabetic cardiomyopathies, Toll-Like receptor 4, NF-kappa B, NACHT-LRR-PYD-containing protein 3