Effect of modulating thrombomodulin expression on renal injury in rats with diabetic nephropathy

Wei WANG; Yi LI; Song WU; Jin CHEN; Yanmei WANG; Yun TANG; Guisen LI; Hanlu DING

doi:10.16016/j.1000-5404.202007105

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Effect of modulating thrombomodulin expression on renal injury in rats with diabetic nephropathy

Basic Medicine | 更新时间：2026-01-09

- Effect of modulating thrombomodulin expression on renal injury in rats with diabetic nephropathy
- Journal of Third Military Medical University Vol. 43, Issue 2, Pages: 156-162(2021)
- 作者机构：
  
  610072 成都，四川省人民医院肾内科，电子科技大学医学院四川省肾脏疾病临床研究中心
- 作者简介：
- 基金信息：
  
  the General Program of National Natural Science Foundation of China(81170680);the Application Fundamental Project of Science and Technology Department of Sichuan Province(2018JY0332);the Research Funds for Young Scholars of Sichuan Provincial People's Hospital(3030503851)
- DOI：10.16016/j.1000-5404.202007105
  CLC： R692.9; TQ937
- Received：12 July 2020，
  
  Revised：2020-09-07，
  
  Published：30 January 2021
- 稿件说明：
移动端阅览
Wei WANG, Yi LI, Song WU, et al. Effect of modulating thrombomodulin expression on renal injury in rats with diabetic nephropathy[J]. Journal of Third Military Medical University, 2021, 43(2): 156-162.
DOI：

Wei WANG, Yi LI, Song WU, et al. Effect of modulating thrombomodulin expression on renal injury in rats with diabetic nephropathy[J]. Journal of Third Military Medical University, 2021, 43(2): 156-162. DOI： 10.16016/j.1000-5404.202007105.

摘要

目的

探讨干预血栓调节蛋白(thrombomodulin，TM)表达对糖尿病肾病(diabetic nephropathy，DN)肾损伤的影响及可能机制。

方法

① 利用免疫组化检测25例DN患者肾组织以及6例正常肾组织中肝X受体-α(liver X receptor-α，LXR-α)、TM、凝血因子XⅢ- A(FXⅢ-A)和CD163表达；②在明确LXR-α激动剂T0901317上调db/db小鼠TM表达及TM干扰RNA(Ad-TM shRNA)下调TM表达作用后，将12周龄雄性db/db小鼠分为4组(

=6):DN生理盐水组、Ad-ctrl+DN组、T0901317+DN组、Ad-TM shRNA+DN组，C57BL6野生小鼠作为正常对照组。上述5组给药4周后，Western blot、免疫组化观察干预TM表达对肾组织TM、LXR-α、FXⅢ-A、CD163表达的影响，ELISA检测血炎症介质(TNF-α、IL-6)以及尿微量白蛋白的变化。

结果

DN患者肾组织TM、LXR-α表达量较对照组下降，且与肾小球滤过率正相关(

0.05)；而FXⅢ-A和CD163表达较对照组升高，且与肾小球滤过率负相关(

0.05)。动物实验显示:DN生理盐水组与野生小鼠对照组相比、Ad-TM shRNA组与DN对照组相比，均表现为尿微量白蛋白和血TNF-α、IL-6水平上升、肾组织TM和LXR-α表达减少、FXⅢ-A和CD163表达增加(

0.05)，而T0901317+DN组较DN对照组，上述指标改善。

结论

表达上调的TM可能通过抑制肾组织FXⅢ-A、CD163表达以及下调血炎症介质水平而改善db/db小鼠尿蛋白水平。

Abstract

Objective

To investigate the effect of modulating thrombomodulin (TM) expression on renal injury in a rat model of diabetic nephropathy (DN) and explore the possible mechanism.

Methods

We examined the expression of liver X receptor-α (LXR-α)

coagulation factor XⅢ-A (FXⅢ-A) and CD163 in 25 renal biopsy samples from patients with DN and in 6 normal renal tissue specimens using immunohistochemistry. Twenty-four 12-week-old male db/db mice with DN were randomly assigned into 4 equal groups and treated daily with intragastric administration of normal saline or LXR-α agonist T0901317

or with intravenous injection of an adenoviral vector carrying TM shRNA or the control adenoviral vector for 7 consecutive days; 6 wild-type C57BL6 mice with intragastric saline treatment served as the normal control group. Four weeks after the treatment

the expression of TM

LXR-α

FXⅢ-A and CD163 in the renal tissues of the mice were detected using Western blotting

the levels of tumor necrosis factor-α (TNF-α) and interleukine-6 (IL-6) were detected by ELISA

and the urinary microalbumin level was determined.

Results

The renal expression levels of TM and LXR-α were decreased (

0.05) and those of FXⅢ-A and CD163 were increased significantly (

0.05) in the kidney tissues of DN patients compared with normal kidney tissues. In db/db mouse model of DN

the expression levels of TM and LXR-α were positively correlated while those of FXⅢ-A and CD163 were negatively correlated with glomerular filtration rate (

0.05). Compared with the wild-type mice

the mouse model of DN showed significantly increased urinary microalbumin levels and serum levels of TNF-α and IL-6

lowered renal expressions of TM and LXR-α

and increased renal expression of FXⅢ-A and CD163; these changes were further exacerbated in the mice treated with Ad-TM shRNA (

0.05) but significantly improved in the mouse models treated with T0901317.

Conclusion

Upregulating TM expression can reduce urinary microalbumin level in db/db mouse model of DN by inhibiting the renal expression of FXⅢ-A and CD163 and downregulating blood levels of inflammatory mediators.

关键词

Keywords

references

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