肾气丸对Zucker糖尿病肥胖大鼠肾损伤、GRP78及自噬相关因子的影响

刘嘉鹏; 冯婧; 车宇娥; 张晓凤; 刘雨梦; 王谦; 李姝玉

doi:10.3969/j.issn.1006-2157.2023.02.013

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肾气丸对Zucker糖尿病肥胖大鼠肾损伤、GRP78及自噬相关因子的影响

实验研究 | 更新时间：2023-03-07

- 肾气丸对Zucker糖尿病肥胖大鼠肾损伤、GRP78及自噬相关因子的影响
- The effects of Shenqi Wan on renal damage, GRP78, and autophagy-related factors in Zucker diabetic fatty rats
- 北京中医药大学学报 2023年46卷第2期页码：224-231
- 作者机构：
  
  北京中医药大学中医学院　北京　102488
- 作者简介：
  
  刘嘉鹏，男，在读硕士生
  #李姝玉，女，博士，副教授，硕士生导师，主要研究方向：中医药对糖尿病及其并发症的防治研究，E-mail: lishuyu@bucm.edu.cn
- 基金信息：
  
  国家自然科学基金项目(81803941)
- DOI：10.3969/j.issn.1006-2157.2023.02.013
  中图分类号： R285.5
- 纸质出版日期：2023-02-28，
  
  网络出版日期：2022-12-28，
  
  收稿日期：2022-07-19，
- 稿件说明：
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刘嘉鹏, 冯婧, 车宇娥, 等. 肾气丸对Zucker糖尿病肥胖大鼠肾损伤、GRP78及自噬相关因子的影响[J]. 北京中医药大学学报, 2023,46(2):224-231.

LIU Jiapeng, FENG Jing, CHE Yu’e, et al. The effects of Shenqi Wan on renal damage, GRP78, and autophagy-related factors in Zucker diabetic fatty rats[J]. Journal of Beijing University of Traditional Chinese Medicine, 2023,46(2):224-231.
刘嘉鹏, 冯婧, 车宇娥, 等. 肾气丸对Zucker糖尿病肥胖大鼠肾损伤、GRP78及自噬相关因子的影响[J]. 北京中医药大学学报, 2023,46(2):224-231. DOI： 10.3969/j.issn.1006-2157.2023.02.013.

LIU Jiapeng, FENG Jing, CHE Yu’e, et al. The effects of Shenqi Wan on renal damage, GRP78, and autophagy-related factors in Zucker diabetic fatty rats[J]. Journal of Beijing University of Traditional Chinese Medicine, 2023,46(2):224-231. DOI： 10.3969/j.issn.1006-2157.2023.02.013.

摘要

目的

研究肾气丸对Zucker糖尿病肥胖(ZDF)大鼠肾脏损伤的影响及其可能机制。

方法

20只雄性8周龄ZDF大鼠给予5C08高脂饲料诱导4周后，随意分为模型组与肾气丸组，7只同周龄雄性Zucker瘦型大鼠为对照组。肾气丸组大鼠每日灌服肾气丸水煎液(8.12 g/kg)，模型组和对照组大鼠每日灌服等量生理盐水，连续给药4周。观察大鼠一般情况并检测空腹血糖(FBG)与24 h尿微量白蛋白(24 h U-mAlb)；观察肾组织病理变化；实时荧光PCR和蛋白质印迹法分别检测肾组织GRP78、Beclin-1和LC3的基因与蛋白表达。

结果

相比于模型组，肾气丸组大鼠表现出较好的一般状态，体质量增长率升高(

0.05)；FBG和24 h U-mAlb有所降低(

0.05)。可见模型组大鼠肾小球毛细血管扩张，基底膜出现不规则增厚，系膜区增宽及节段性硬化，肾小管萎缩，肾间质纤维组织增生，足细胞足突融合，线粒体和内质网溶解及自噬小体数量减少。肾气丸组大鼠肾脏病理改变减轻。与模型组相比，肾气丸组大鼠肾组织GRP78基因和蛋白表达水平降低(

0.05)，Beclin-1蛋白表达水平降低(

0.05)，LC3蛋白表达水平升高(

0.05)。

结论

肾气丸可能通过缓解内质网应激并促进自噬来减轻2型糖尿病动物ZDF大鼠的肾组织损伤，延缓糖尿病肾脏疾病进展。

Abstract

Objective

To investigate the effects of

Shenqi Wan

on renal damage in Zucker diabetic fatty (ZDF) rats and the underlying mechanisms.

Methods

Twenty 8-week-old male ZDF rats were given 5C08 high-fat fodder for four weeks to induce diabetes. ZDF rats were randomly divided into the model group and the

Shenqi Wan

group. Seven male Zucker lean rats of the same age were used as the control group. Rats in the

Shenqi Wan

group were given

Shenqi Wan

decoction (8.12 g/kg). Rats in the model group and the control group were given the same amount of normal saline. Rats were continuously administered for 4 weeks. The general condition of rats was observed regularly. The fasting blood glucose (FBG) and 24-hour urinary microalbumin (24 h U-mAlb) levels were measured. Renal tissue was stained and morphology was observed. The ultra-microstructure was observed by transmission electron microscopy. The mRNA levels of GRP78

Beclin-1

and LC3 in rat renal tissue were examined by real-time PCR and the protein levels were examined by Western blotting.

Results

Compared with the model group

rats in the

Shenqi Wan

group showed improved fur gloss

more weight increase(

0.05); both FBG and 24 h U-mAlb levels were decreased (

0.05). The kidneys of rats in the model group showed dilated glomerular capillaries

irregularly thickened basement membranes

widened mesangial areas

and segmental sclerosis; renal tubular atrophy and renal interstitial fibrous tissue were also observed in these kidneys. These pathological changes were alleviated in the

Shenqi Wan

group. Compared with the model group

both gene and protein levels of GRP78 were decreased (

0.05) in the

Shenqi Wan

group; the protein level of Beclin-1 was decreased (

0.05); and the protein level of LC3 was increased (

0.05).

Conclusion

Shenqi Wan

may alleviate renal damage in ZDF rats with type 2 diabetes mellitus and delay the progression of diabetic kidney disease by reducing endoplasmic reticulum stress and enhancing autophagy.

关键词

肾气丸2型糖尿病糖尿病肾脏疾病内质网应激自噬GRP78Zucker糖尿病肥胖大鼠

Keywords

Shenqi Wantype 2 diabetes mellitusdiabetic kidney diseaseendoplasmic reticulum stressautophagyGRP78Zucker diabetic fatty rats

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