穿心莲内酯对糖尿病足大鼠血管生成的影响及机制

张丽晓; 戴守方; 李蕾; 王瑞锋; 杨丽丽; 邱金霞; 尹永波

doi:10.6039/j.issn.1001-0408.2023.17.14

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穿心莲内酯对糖尿病足大鼠血管生成的影响及机制

药学研究 | 更新时间：2023-09-14

- 穿心莲内酯对糖尿病足大鼠血管生成的影响及机制
- Effects of andrographolide on angiogenesis in diabetic foot rats and its mechanism
- 中国药房 2023年34卷第17期页码：2128-2133
- 作者机构：
  
  1.邢台市人民医院中医内科，河北邢台 054000
  2.邢台市人民医院放射科，河北邢台　054000
  3.邢台市人民医院内分泌科，河北邢台　054000
  4.邢台市人民医院耳鼻喉科，河北邢台　054000
- 作者简介：
  
  副主任中医师，硕士。研究方向：糖尿病及其并发症。电话：0319-3138801。E-mail：zhanglixiao2005@163.com
- 基金信息：
  
  邢台市科技计划项目(2018ZC212)
- DOI：10.6039/j.issn.1001-0408.2023.17.14
  中图分类号： R965;R285.5
- 纸质出版日期：2023-09-15，
  
  收稿日期：2023-03-02，
  
  修回日期：2023-08-08，
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张丽晓,戴守方,李蕾等.穿心莲内酯对糖尿病足大鼠血管生成的影响及机制 ^Δ[J].中国药房,2023,34(17):2128-2133.

ZHANG Lixiao,DAI Shoufang,LI Lei,et al.Effects of andrographolide on angiogenesis in diabetic foot rats and its mechanism[J].ZHONGGUO YAOFANG,2023,34(17):2128-2133.
张丽晓,戴守方,李蕾等.穿心莲内酯对糖尿病足大鼠血管生成的影响及机制 ^Δ[J].中国药房,2023,34(17):2128-2133. DOI： 10.6039/j.issn.1001-0408.2023.17.14.

ZHANG Lixiao,DAI Shoufang,LI Lei,et al.Effects of andrographolide on angiogenesis in diabetic foot rats and its mechanism[J].ZHONGGUO YAOFANG,2023,34(17):2128-2133. DOI： 10.6039/j.issn.1001-0408.2023.17.14.

摘要

目的

探究穿心莲内酯（Andro）对糖尿病足大鼠血管生成的影响，并基于Hippo-Yes相关蛋白（YAP）信号通路探索其作用机制。

方法

采用小剂量链脲佐菌素联合高脂高糖饮食复制2型糖尿病大鼠模型，在其建模成功的基础上，用烫伤法建立糖尿病足大鼠模型。将造模成功的大鼠随机分为5组，每组12只：Model组，Andro低、中、高剂量组（1、10、20 mg/kg）和抑制剂组（20 mg/kg Andro+100 mg/kg的Hippo-YAP信号通路特异性抑制剂维替泊芬）。另外取12只健康大鼠作为Control组。各组大鼠灌胃和腹腔注射溶剂或相应药物，每日1次，连续2周。给药结束后，检测大鼠创面愈合情况、空腹血糖（FBG）和空腹胰岛素（FINS）含量；以HE染色法观察大鼠创面组织损伤及毛细血管数；采用流式细胞仪进行大鼠外周血内皮祖细胞（EPCs）计数；采用全自动生化分析仪检测大鼠血清总胆固醇（TC）、甘油三酯（TG）、高密度脂蛋白胆固醇（HDL-C）、低密度脂蛋白胆固醇（LDL-C）含量；采用Western blot法检测各组大鼠创面组织中缺氧诱导因子1α（HIF-1α）、血管内皮生长因子（VEGF）及Hippo-YAP信号通路相关蛋白的表达情况。

结果

与Control组比较，Model组大鼠创面愈合率，毛细血管数，EPCs比例，HDL-C含量，HIF-1α、VEGF蛋白表达水平及哺乳动物Ste20样激酶1、大肿瘤抑制基因1、YAP蛋白的磷酸化水平均显著降低，FBG、FINS水平及TC、TG、LDL-C含量均显著升高（

＜0.05）。与Model组比较，Andro低、中、高剂量组大鼠上述指标均显著逆转，且呈剂量依赖性（

＜0.05）；维替泊芬减弱了Andro的上述逆转作用（

＜0.05）。

结论

Andro具有降低糖尿病足大鼠血糖、血脂，促进糖尿病足大鼠血管生成及创面愈合的作用，其作用机制可能与激活Hippo-YAP信号通路有关。

Abstract

OBJECTIVE

To investigate the effects of andrographolide （Andro） on angiogenesis in rats with diabetic foot and to explore its mechanism of action based on the Hippo-Yes-associated protein （YAP） signaling pathway.

METHODS

The rat model of type 2 diabetes was established by using low-dose streptozotocin combined with high-fat and high-glucose diet. On the basis of successful modeling， the rat model of diabetes foot was established by scalding. Model rats were randomly divided into 5 groups with 12 rats in each group： model group， Andro low-dose， medium-dose， and high-dose groups （1， 10， and 20 mg/kg）， as well as inhibitor group （20 mg/kg Andro+100 mg/kg of verteporfin， an specific inhibitor of Hippo-YAP signaling pathway）； other 12 healthy rats were included in the Control group. Rats in each group were intragastrically and intraperitoneally injected with solvents or corresponding drugs， once a day， for 2 consecutive weeks. The wound healing， fasting blood glucose （FBG） and fasting insulin （FINS） were detected in rats after medication. HE staining was performed to observe the tissue damage and capillary number of rat trauma； the number of endothelial progenitor cells （EPCs） in peripheral blood of rats was counted by using flow cytometry； the contents of serum total cholesterol （TC）， triglyceride （TG）， high-density lipoprotein cholesterol （HDL-C） and low-density lipoprotein cholesterol （LDL-C） in rats were determined by fully automatic biochemical analyzer； the expressions of hypoxia-inducible factor 1α （HIF-1α）， vascular endothelial growth factor （VEGF） and Hippo-YAP signaling pathway-related proteins in the traumatic tissues of rats in each group were detected by Western blot.

RESULTS

Compared with Control group， the wound healing rate， capillary number， the proportion of EPCs， HDL-C content， as well as the protein expression levels of HIF-1α and VEGF and the phosphorylation levels of mammalian Ste20-like kinase 1， large tumor suppressor gene 1 and YAP proteins were significantly reduced in the model group， while the FBG， FINS levels and TC， TG and LDL-C contents were significantly increased （

＜0.05）. Compared with model group， the above indexes were significantly reversed in Andro low-dose， medium-dose and high-dose group， in a dose-dependent manner （

＜0.05）； verteporfin attenuated the above reversal effect of Andro （

＜0.05）.

CONCLUSIONS

Andro has the effects of lowering blood glucose and blood lipids， promoting blood vessel formation and wound healing in rats with diabetic foot， and its mechanism of action may be related to the activation of Hippo-YAP signaling pathway.

关键词

穿心莲内酯糖尿病足血管生成Hippo-Yes相关蛋白信号通路

Keywords

diabetic footangiogenesisHippo-YAP signaling pathway

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