Prevention of renal interstitial fibrosis by osthole in diabetic nephropathy model mice

HUANG Qian; ZHENG Dandan; HUANG Qiuhong; SHI Zilu

doi:10.6039/j.issn.1001-0408.2022.22.06

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Prevention of renal interstitial fibrosis by osthole in diabetic nephropathy model mice

更新时间：2025-09-26

- Prevention of renal interstitial fibrosis by osthole in diabetic nephropathy model mice
- ZHONGGUO YAOFANG Vol. 33, Issue 22, Pages: 2719-2723(2022)
- 作者机构：
  
  1.泉州医学高等专科学校基础医学部生理教研室，福建泉州　362100
  2.福建医科大学附属泉州第一医院肾内科，福建泉州　362000
- 作者简介：
- 基金信息：
- DOI：10.6039/j.issn.1001-0408.2022.22.06
  CLC： R965
- Received：27 May 2022，
  
  Revised：2022-09-21，
  
  Published：30 November 2022
- 稿件说明：
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黄倩,郑丹丹,黄秋虹,等.蛇床子素对糖尿病肾病模型小鼠肾间质纤维化的预防作用[J].中国药房,2022,33(22):2719-2723.

HUANG Qian,ZHENG Dandan,HUANG Qiuhong,et al.Prevention of renal interstitial fibrosis by osthole in diabetic nephropathy model mice[J].ZHONGGUO YAOFANG,2022,33(22):2719-2723.
黄倩,郑丹丹,黄秋虹,等.蛇床子素对糖尿病肾病模型小鼠肾间质纤维化的预防作用[J].中国药房,2022,33(22):2719-2723. DOI： 10.6039/j.issn.1001-0408.2022.22.06.

HUANG Qian,ZHENG Dandan,HUANG Qiuhong,et al.Prevention of renal interstitial fibrosis by osthole in diabetic nephropathy model mice[J].ZHONGGUO YAOFANG,2022,33(22):2719-2723. DOI： 10.6039/j.issn.1001-0408.2022.22.06.

摘要

目的

探讨蛇床子素（OST）对糖尿病肾病（DN）模型小鼠肾间质纤维化的影响。

方法

采用一次性尾静脉注射链脲佐菌素建立糖尿病小鼠模型，成功后继续喂养12周建立DN模型。将糖尿病模型小鼠分为模型组和OST低、中、高剂量（20、40、80 mg/kg）组，每组10只，糖尿病造模成功后每日灌胃相应药物或溶剂（模型组）1次，持续12周；同时设置正常对照组。末次灌胃后，检测各组小鼠空腹血糖、24 h尿蛋白、血肌酐（Scr）、尿素氮水平；Masson染色法观察肾间质区域胶原纤维的沉积情况；免疫组化染色法检测肾皮质中E-钙黏蛋白（E-cadherin）和波形蛋白（vimentin）的表达；Western blot法检测肾皮质中卵泡抑素样蛋白1（Fstl1）、锌指转录因子1（Snail1）蛋白表达和蛋白激酶B（Akt）磷酸化水平（以p-Akt/Akt比值计）。

结果

与正常对照组比较，模型组小鼠空腹血糖、24 h尿蛋白、Scr、尿素氮水平，肾间质胶原纤维沉积占比，肾皮质中vimentin表达水平以及Fstl1、Snail1蛋白表达水平和p-Akt/Akt比值均显著升高（

＜0.01），E-cadherin表达水平显著降低（

＜0.01）。与模型组比较，OST各剂量组小鼠上述指标变化均显著逆转（

＜0.05或

＜0.01）。

结论

OST预防性用药可有效降低DN模型小鼠的空腹血糖，保护其肾功能，抑制肾小管上皮细胞间充质转分化，延缓肾间质纤维化进程，其作用机制可能与抑制Fstl1/Akt/Snail1通路有关。

Abstract

OBJECTIVE

To investigate the effects of osthole （OST） on renal interstitial fibrosis in diabetic nephropathy （DN） model mice.

METHODS

The diabetic mice model was established by the tail vein injection of streptozotocin once， and the DN model was established by feeding for 12 weeks after successful modeling of diabetes. Diabetic model mice were randomly divided into model group， low-dose， moderate-dose， high-dose groups （20， 40， 80 mg/kg） of OST， with 10 mice in each group. After successful modeling of diabetes， the mice were given corresponding drugs or solvent （model group） intragastrically， once a day， for consecutive 12 weeks， and the normal control group was set up at the same time. After the last administration， the levels of fasting blood glucose， 24 h urinary protein， serum creatinine （Scr） and blood urea nitrogen were tested in each group. Masson staining was used to observe the deposition of collagen fibers in renal interstitium； the expressions of E-cadherin and vimentin in renal cortex were detected by immunohistochemical staining. The protein expressions of follistatin-like protein 1 （Fstl1） and Snail family transcriptional repressor 1 （Snail1）， the phosphorylation of protein kinase B （Akt）（calculated by p-Akt/Akt） in the renal cortex were detected by Western blot.

RESULTS

Compared with normal control group， the levels of fasting blood glucose， 24 h urinary protein， Scr and blood urea nitrogen， collagen fiber deposition ratio of renal interstitium， the expression of vimentin， protein expressions of Fstl1 and Snail1， p-Akt/Akt in renal cortex were increased significantly （

＜0.01）， as well as the expression of E-cadherin was decreased significantly （

＜0.01）. Compared with model group， above indexes of OST groups were reversed significantly （

＜0.05 or

＜0.01）.

CONCLUSIONS

Preventive use of OST can effectively reduce fasting blood glucose level， protect renal function and inhibit epithelial-mesenchymal transition of DN model mice， and delay the progression of renal interstitial fibrosis ， the mechanism of which may be associated with the suppression of Fstl1/Akt/Snail1 signaling pathway.

关键词

Keywords

references

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