主 办:北 京 中 医 药 大 学
ISSN 1006-2157 CN 11-3574/R

北京中医药大学学报 ›› 2017, Vol. 40 ›› Issue (1): 20-26.doi: 10.3969/j.issn.1006-2157.2017.01.005

• 博士之光 • 上一篇    下一篇

红芪多糖对db/db小鼠糖尿病心肌病TGF-β1/Smads   信号通路影响的实验研究*

金智生1,王东旭1,张花治1,和彩玲1,南向萍1,王倩2,楚惠媛1   

  1. 1 甘肃中医药大学 甘肃 730000;
    2 保定市第一中医院
  • 收稿日期:2016-09-02 出版日期:2017-01-30 发布日期:2017-01-30
  • 作者简介:金智生,男,教授,博士生导师
  • 基金资助:
    *国家自然科学基金项目(No.81360538)

Effect of hedysarum polybotrys polysacchcaide on TGF-β1/Smads signaling pathway in db/db mice with diabetic cardiomyopathy*

JIN Zhisheng1, WANG Dongxu1,ZHANG Huazhi1,HE Cailing1,NAN Xiangping1,WANG Qian2,CHU Huiyuan1   

  1. 1 Gansu University of Traditional Chinese Medicine,Gansu 730000;
    2 First Hospital of Chinese Medicine of Baoding,Hebei
  • Received:2016-09-02 Online:2017-01-30 Published:2017-01-30

摘要: 目的 通过研究红芪多糖(HPS)对db/db小鼠糖尿病心肌病(DCM)心肌组织中TGF-β1/Smads信号通路的影响,探讨其对DCM小鼠心肌纤维化的影响。方法 将60只6周龄雄性db/db小鼠随机分为5组:HPS高、中、低剂量组,罗格列酮组和模型组;正常组为12只同周龄同背景的非转基因雄性db/m小鼠。连续灌胃干预8周。于给药前及给药后第2、4、6、8周末检测各组小鼠体重、血糖;HE染色观察小鼠左心室心肌纤维病理形态学变化;Masson染色观察小鼠左心室心肌胶原纤维化程度;Western blot、RT-PCR法检测心肌组织TGF-β1及Smad2、Smad3蛋白和mRNA的表达。结果 经HPS治疗8周后,HPS高、中剂量组和罗格列酮组血糖较模型组下降明显(P<0.05);HE染色可见模型组心肌细胞结构模糊,部分区域明显肿胀变形且细胞核消失;Masson染色可见亮绿色胶原纤维在模型组心肌细胞间及血管周围较正常组明显增多且呈堆积状分布;模型组TGF-β1及Smad2、Smad3蛋白及mRNA的表达水平与HPS低剂量组无显著差异(P>0.05),其余各治疗组较模型组明显降低(P<0.05),其中HPS高剂量组和罗格列酮组改善更明显(P<0.05)。结论 HPS可改善db/db小鼠DCM心肌纤维化的程度,延缓DCM病情进展,其作用机制可能与其抑制TGF-β1/Smads信号通路有关。

关键词: 糖尿病心肌病, 红芪多糖, TGF-β1/Smads信号通路, db/db小鼠

Abstract: Objective To explore the effect of hedysarum polybotrys polysacchcaide (HPS) on myocardial fibrosis of db/db mice with diabetic cardiomyopathy (DCM) by taking TGF-β1/Smads signaling pathway as the index. Methods Altogether 60 six-week-old male db/db mice were randomly divided into five groups: HPS high-,mid-,low- dose group, rosiglitazone group and model group, additional 12 non transgenic db/m male mice with the same background were assigned into the normal group. The mice except for those of the normal group were intragatrically administered (i.g.) corresponding medicines for consecutive 8 weeks. Before treatment and every two weeks during the period of i.g. drugs, the body weight and blood glucose were detected. At the end of Week 8, HE staining was used to observe the pathological changes of left ventricular myocardial fibers, Masson staining was used to observe the degree of left ventricular myocardial collagen fibrosis, and Western blot, RT-PCR were used to measure the protein and mRNA expressions of TGF-β1 and Smad2, Smad3 in cardiac muscle tissue. Results Eight weeks after treatment, the blood glucose of rats in HPS high-, mid- dose group, and rosiglitazone group decreased significantly compared with model group (P<0.05). The sections of HE staining showed that the model rats’ myocardial cells structure became unclear and some of them were swollen and deformed obviously, even the nucleus disappeared. The sections of Masson staining showed that bright green collagen fibers were heaped up between myocardial cells and around blood vessels of the model rats. The protein and mRNA expressions of TGF-β1, Smad2 and Smad3 had no significant difference between model group and HPS low-dose group (P>0.05), but the other groups decreased significantly compared with the model group (P<0.05), especially the HPS high-dose group or rosiglitazone group was superior to mid-dose group (P<0.05). Conclusion The effect of HPS against myocardial fibrosis in db/db mice with DCM to slow down the progression of DCM was proved, and its potential mechanism may be related to inhibitation of TGF-β1/Smads signaling pathway.

Key words: diabetic cardiomyopathy, hedysarum polybotrys polysacchcaide, TGF-β1/Smads signaling pathway, db/db mice

中图分类号: 

  • R285.5