Niclosamide ethanolamine improves kidney injury in db/db mice

被引：23

作者：

Han, Pengxun ^{[1
]}

Zhan, Hongyue ^{[1
]}

Shao, Mumin ^{[2
]}

Wang, Wenjing ^{[1
]}

Song, Gaofeng ^{[1
]}

Yu, Xuewen ^{[2
]}

Zhang, Chunlei ^{[3
]}

Ge, Na ^{[1
]}

Yi, Tiegang ^{[1
]}

Li, Shunmin ^{[1
]}

Sun, Huili ^{[1
]}

机构：

[1] Guangzhou Univ Chinese Med, Clin Med Coll 4, Shenzhen Tradit Chinese Med Hosp, Dept Nephrol, 1 Fuhua Rd, Shenzhen 518033, Guangdong, Peoples R China

[2] Guangzhou Univ Chinese Med, Clin Med Coll 4, Shenzhen Tradit Chinese Med Hosp, Dept Pathol, Shenzhen, Guangdong, Peoples R China

[3] Guangzhou Univ Chinese Med, Clin Med Coll 4, Shenzhen Tradit Chinese Med Hosp, Dept Clin Lab, Shenzhen, Guangdong, Peoples R China

来源：

DIABETES RESEARCH AND CLINICAL PRACTICE | 2018年 / 144卷

基金：

中国国家自然科学基金;

关键词：

Diabetic kidney disease; Niclosamide ethanolamine salt; mTOR/4E-BP1; KINASE-C-ALPHA; DIABETIC-NEPHROPATHY; MAMMALIAN TARGET; MTOR; INHIBITION; ACTIVATION; MECHANISMS; BLOCKADE; DISEASE; GROWTH;

D O I：

10.1016/j.diabres.2018.08.003

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

Aims: Early diabetic kidney disease (DKD) is characterized by renal hypertrophy and albuminuria. The mTOR signal pathway is closely related to DKD. This study was performed to determine the renal protection of niclosamide ethanolamine salt (NEN) which was identified as mTOR inhibitor. Methods: Type 2 diabetes (T2D) db/db mice were used and divided into db/db and db/db + NEN groups. Lean wild type mice served as T2D-control. NEN treatment lasted for 12 weeks. The kidney morphological changes, urine indices, blood glucose and metabolic symptoms were evaluated. In addition, the effects of NEN on kidney mitochondria and mTOR/4E-BP pathway were also measured. Results: NEN could prevent diabetic kidney hypertrophy and alleviate glomerular mesangial expansion, attenuate GBM and TBM thickening in db/db mice. It also restored podocyte dysfunction, reduced urinary albumin, NAG, NGAL, and TGF-beta 1 excretion. Specifically, it could uncouple kidney mitochondria and significantly inhibit renal cortical activation of mTOR/4E-BP1 pathway. Conclusions: This study demonstrated that NEN could improve kidney injury in db/db mice and has the potential to translate to future clinical studies. (C) 2018 Elsevier B.V. All rights reserved.

引用

页码：25 / 33

页数：9

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