雌马酚对2型糖尿病大鼠的肾脏保护作用

李硕; 倪向敏; 徐喆; 张贵明; 崔涵强; 王建

doi:10.16016/j.2097-0927.202110145

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雌马酚对2型糖尿病大鼠的肾脏保护作用

基础医学 | 更新时间：2026-01-09

- 雌马酚对2型糖尿病大鼠的肾脏保护作用
- Renal protective effect of equol on type 2 diabetic rats
- 陆军军医大学学报 2022年44卷第10期页码：1009-1017
- 作者机构：
  
  400037 重庆，陆军军医大学(第三军医大学)第二附属医院营养科
- 作者简介：
  
  [王建，E-mail: wangjian_1996@aliyun.com WANG Jian, E-mail: wangjian_1996@aliyun.com
- 基金信息：
  
  国家自然基金面上项目(81973040);国家自然基金青年科学基金项目(81602855)
- DOI：10.16016/j.2097-0927.202110145
  中图分类号： R282.71;R587.1;R692
- 收稿：2021-10-25，
  
  修回：2022-01-11，
  
  纸质出版：2022-05-30
- 稿件说明：
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李硕, 倪向敏, 徐喆, 等. 雌马酚对2型糖尿病大鼠的肾脏保护作用[J]. 陆军军医大学学报, 2022,44(10):1009-1017.

Shuo LI, Xiangmin NI, Zhe XU, et al. Renal protective effect of equol on type 2 diabetic rats[J]. Journal of Army Medical University, 2022, 44(10): 1009-1017.
李硕, 倪向敏, 徐喆, 等. 雌马酚对2型糖尿病大鼠的肾脏保护作用[J]. 陆军军医大学学报, 2022,44(10):1009-1017. DOI： 10.16016/j.2097-0927.202110145.

Shuo LI, Xiangmin NI, Zhe XU, et al. Renal protective effect of equol on type 2 diabetic rats[J]. Journal of Army Medical University, 2022, 44(10): 1009-1017. DOI： 10.16016/j.2097-0927.202110145.

摘要

目的

探讨雌马酚(equol，Eq)对2型糖尿病(type 2 diabetes mellitus，T2DM)大鼠的肾脏保护效应和对肾组织氧化应激、炎症因子水平的影响及其可能作用机制。

方法

选取6周龄SD大鼠50只，对照组(

=10)给予普通饲料喂养；40只高脂高糖饮食联合链脲佐菌素腹腔注射建立T2DM大鼠模型，建模成功34只，T2DM模型组(

=9)给予高脂高糖饲料喂养，Eq干预组在模型组基础上分别给予低剂量(EqL，20 mg·kg

-1

·d

-1

，

=9)、中剂量(EqM，40 mg·kg

-1

·d

-1

，

=8)、高剂量(EqH，80 mg·kg

-1

·d

-1

，

=8)Eq灌胃干预。连续干预12周后，检测大鼠血清肌酐(creatinine，CREA)、尿素氮(blood urea nitrogen

BUN)、尿酸(uric acid，UA)及肾组织氧化应激、炎症因子指标水平，HE、PAS染色显示肾组织显微结构变化，Western blot及RT-PCR检测肾组织核因子E2相关因子2(nuclear factor erythroid 2-related factor 2，Nrf2)/血红素氧合酶-1(heme oxygenase 1，HO-1)通路激活/抑制情况。

结果

干预12周后，与对照组相比，模型组T2DM大鼠血清CREA、BUN、UA水平显著升高(

0.05)，肾组织丙二醛(malondialdehyde，MDA)、TNF-α等氧化应激及炎症指标水平显著升高(

0.05)，HE、PAS染色结果显示肾小球体积增大、系膜基质增多，肾小囊基底膜增厚，肾小管萎缩、管腔扩张，肾组织总Nrf2、HO-1蛋白和mRNA表达水平及核Nrf2蛋白水平显著降低(

0.05)；与模型组相比，各Eq干预组血清CREA、BUN、UA水平显著降低(

0.05)，肾组织MDA、TNF-α等氧化应激及炎症指标水平显著降低(

0.05)，HE、PAS染色结果显示肾显微结构损伤明显减轻，总Nrf2、HO-1蛋白和mRNA表达水平及核Nrf2蛋白水平显著升高(

0.05)，各Eq干预组组间相比差异无统计学意义。

结论

雌马酚能够降低T2DM大鼠肾脏组织氧化应激和炎症因子水平，发挥肾脏保护效应，Nrf2/HO-1通路可能在其中发挥重要作用。

Abstract

Objective

To investigate the effect of equol (Eq) on oxidative stress and inflammatory factors in renal tissue in type 2 diabetes mellitus (T2DM) rats

and explore the possible mechanism in the process.

Methods

Fifty SD rats aged 6 weeks were selected

and 40 of them were given high-fat and high-sugar diet combined with intraperitoneal injection of streptozotocin to establish T2DM rat model

and finally 34 out of 40 were successfully modeled. The rats from the control group (

=10) was fed with ordinary diet

and the T2DM rats were further divided into model group (

=9)

and low-(

=9)

medium-(

=8) and high-dose (

=8) Eq intervention groups (gavage intervention of 20

40 and 80 mg/kg Eq

respectively). After 12 consecutive weeks of intervention

serum creatinine (CREA)

blood urea nitrogen (BUN)

uric acid (UA)

and levels of renal oxidative stress and inflammatory factors were detected in each group of rats. HE and PAS stainings were adopted to reveal the histological changes of renal tissue. Western blotting and RT-PCR were performed to determine the activation or inhibition of nuclear factor erythroid 2-related factor 2 (Nrf2)/heme oxygenase 1 (HO-1) pathway in renal tissue.

Results

As compared with the control group

the serum levels of CREA

BUN and UA were significantly increased in the T2DM model group (

0.05)

and the levels of oxidative stress and inflammation indicators such as malondialdehyde (MDA) and TNF-α in renal tissue were remarkably elevated as well (

0.05). The results of HE and PAS stainings showed increased glomerular volume and mesangial matrix

thickened basement membrane of renal capsule

atrophy of renal tubules and dilation of lumen in the model group. Moreover

the protein and mRNA levels of total Nrf2 and HO-1

as well as the expression of nuclear Nrf2 protein were all greatly reduced (

0.05). In comparison with the model group

the serum levels of CREA

BUN and UA in the 3 Eq intervention groups were significantly decreased (

0.05)

levels of oxidative stress and inflammation indexes in renal tissue were reduced (

0.05)

and the damage of renal microstructure was notably improved. In addition

the protein and mRNA expression of total Nrf2 and HO-1

and nuclear Nrf2 protein level were obviously enhanced (

0.05). There was no statistical difference among Eq intervention groups.

Conclusion

Eq reduces the levels of oxidative stress and inflammatory factors in the renal tissue of T2DM rats

exerting a protective effect on the kidney

in which Nrf2/HO-1 pathway may play an important role.

关键词

Keywords

references

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