T0901317 improves renal injury in db/db mice by activating liver X receptor α

Song WU; Yaqin DU; Ping ZHANG; Wei WANG; Shasha CHEN; Guisen LI; Li WANG; Hanlu DING

doi:10.16016/j.1000-5404.201907232

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T0901317 improves renal injury in db/db mice by activating liver X receptor α

Basic Medicine | 更新时间：2026-01-09

- T0901317 improves renal injury in db/db mice by activating liver X receptor α
- Journal of Third Military Medical University Vol. 42, Issue 1, Pages: 75-80(2020)
- 作者机构：
  
  610072 成都, 电子科技大学医学院, 四川省人民医院肾内科
- 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)
- DOI：10.16016/j.1000-5404.201907232
  CLC： R692.9;R966;R977.6
- Received：29 July 2019，
  
  Revised：2019-09-21，
  
  Published：15 January 2020
- 稿件说明：
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Song WU, Yaqin DU, Ping ZHANG, et al. T0901317 improves renal injury in db/db mice by activating liver X receptor α[J]. Journal of Third Military Medical University, 2020, 42(1): 75-80.
DOI：

Song WU, Yaqin DU, Ping ZHANG, et al. T0901317 improves renal injury in db/db mice by activating liver X receptor α[J]. Journal of Third Military Medical University, 2020, 42(1): 75-80. DOI： 10.16016/j.1000-5404.201907232.

摘要

目的

观察肝X受体(liver X receptor，LXR)激动剂T0901317、血栓调节蛋白(thrombomodulin，TM)干扰RNA重组腺病毒Ad-TMshRNA对db/db糖尿病肾病(diabetic nephropathy

DN)小鼠肾损伤的影响。

方法

12周龄雄性db/db小鼠36只，应用随机数字表法进行分组，分为DN生理盐水组、Ad-ctrl+DN组、Ad-TM shRNA+DN组、T0901317+DN组、Ad-TMshRNA+T0901317+DN组和Ad-ctrl+T090131+DN组

每组6只小鼠。2.5×10

pfu Ad-TMshRNA和Ad-ctrl分别通过尾静脉注射到对应组小鼠，1周后T0901317按0.5 mg/(kg·d)灌胃对应组小鼠且连续给药7 d。4周后

采用Western blot检测小鼠肾组织LXRα、LXRβ、VCAM-1和ICAM-1表达; 检测血肌酐水平

同周龄雄性野生C57BL/6小鼠给予生理盐水胃饲作为正常对照组。

结果

DN组、Ad-ctrl+DN组较野生小鼠，其肾组织LXRα表达下降(

0.05)，与DN、Ad-ctrl+DN组和Ad-TMshRNA+DN组比较，T0901317+DN组、Ad-TMshRNA+T0901317+DN组、Ad-ctrl+T0901317+DN组小鼠肾组织LXRα表达增加(

0.05)。DN各组小鼠LXRβ表达较野生鼠下降，T0901317对DN各组小鼠肾组织LXRβ表达无显著影响。DN组、Ad-ctrl+DN组较野生小鼠，血肌酐、肾组织VCAM-1和ICAM-1表达升高、肾组织病理损伤加重(

0.05)，与DN对照组比较，Ad-TMshRNA沉默组小鼠肾组织损伤加重、肾组织VCAM-1和ICAM-1表达增加(

0.05)，而T0901317+DN和Ad-ctrl+T0901317+DN组小鼠肾损伤减轻、VCAM-1和ICAM-1表达减少(

0.05)。

结论

T0901317可能通过激活LXRα减少VCAM-1和ICAM-1表达从而改善db/db小鼠肾损伤。

Abstract

Objective

To determine the effects of liver X receptor (LXR) agonist T0901317 and thrombomodulin (TM) interfering RNA recombinant adenovirus Ad-TM shRNA on renal injury of db/db mice with diabetic nephropathy (DN).

Methods

A total of 36 male db/db mice (12 weeks old) were randomly assigned into 6 groups (

=6)

DN group

Ad-ctrl+DN group

Ad-TMshRNA+DN group

T0901317+DN group

Ad-TMshRNA+T0901317+DN group and Ad-ctrl+T0901317+DN group. PBS

2.5×10

pfu Ad-TM shRNA and Ad-ctrl were injected into mice through tail vein to corresponding mice

while 0.5 mg/(kg·d) T0901317 was intragastrically administered to the corresponding mice for 7 consecutive days. After treatment for 4 weeks

the kidney tissues were collected for detecting the expression of LXRα

LXRβ

VCAM-1 and ICAM-1 by Western blotting. The serum creatinine level was also detected in all the mice. Male wild-type C57BL/6 mice at the same age served as normal control.

Results

The expression of LXRα in kidney tissue was significantly lower in the DN group and Ad-ctrl+DN group than the wild-type mice (

0.05)

but was obviously higher in the T0901317+DN group

the Ad-TMshRNA+T0901317+DN group and the Ad-ctrl+T0901317+DN group than the DN group

Ad-ctrl+DN group and the Ad-TM shRNA+DN group (

0.05). The expression of LXRβ in DN mice was notably lower than that in the wild-type mice (

0.05). T0901317 had no significant effect on the LXRβ expression in renal tissue of DN mice. The DN control group and Ad-ctrl+DN group had significantly higher serum level of creatinine and renal expression of VCAM-1 and ICAM-1

and aggravated renal pathological damages when compared with the wild-type mice (

0.05). When compared with the DN group

Ad-TMshRNA silenced mice groups had severer renal damages and elevated expression of VCAM-1 and ICAM-1 (

0.05)

while the renal damages were alleviated and the expression of VCAM-1 and ICAM-1 were decreased in the T0901317+DN group and the Ad-ctrl+T0901317+DN group (

0.05).

Conclusion

T0901317 improves renal injury in db/db mice by activating LXRα to reduce the expression of VCAM-1 and ICAM-1.

关键词

Keywords

references

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