Aminophylline suppresses chronic renal failure progression by activating SIRT1/AMPK/mTOR-dependent autophagy  

作　　者：Xin Liao Jieyi Lu Zhifeng Huang Jinai Lin Miao Zhang Huanru Chen Xiaoqing Lin Xia Gao Sitang Gong 

机构地区：[1]Pediatric Department,the First Affiliated Hospital of Jinan University,Guangzhou 510030,China [2]Department of Nephrology,Guangzhou Women and Children’s Medical Center,Guangzhou Medical University,Guangzhou 510623,China [3]Department of Burns and Wound Repair Surgery,Guangdong Provincial People’s Hospital,Guangdong Academy of Medical Sciences,Guangzhou 510080,China

出　　处：《Acta Biochimica et Biophysica Sinica》2024年第9期1311-1322,共12页生物化学与生物物理学报（英文版）

基　　金：supported by the grant from the Project of Guangzhou's Science and Technology Research(No.201904010476).

摘　　要：Chronic renal failure(CRF)is a severe syndrome affecting the urinary system for which there are no effective therapeutics.In this study,we investigate the effects and mechanisms of aminophylline in preventing CRF development.A rat model of chronic renal failure is established by 5/6 nephrectomy.The levels of serum creatinine(SCR),urinary protein(UPR),and blood urea nitrogen(BUN)are detected by ELISA.Histological evaluations of renal tissues are performed by H&E,Masson staining,and PAS staining.Functional protein expression is detected by western blot analysis or immunofluorescence microscopy.Glomerular cell apoptosis is determined using the TUNEL method.Results show that Aminophylline significantly reduces the levels of SCR,UPR,and BUN in the CRF model rats.Histological analyses show that aminophylline effectively alleviates renal tissue injuries in CRF rats.The protein expression levels of nephrin,podocin,SIRT1,p-AMPK,and p-ULK1 are greatly increased,while p-mTOR protein expression is markedly decreased by aminophylline treatment.Additionally,the protein level of LC3B in CRF rats is significantly increased by aminophylline.Moreover,aminophylline alleviates apoptosis in the glomerular tissues of CRF rats.Furthermore,resveratrol promotes SIRT1,p-AMPK,and p-ULK1 protein expressions and reduces p-mTOR and LC3B protein expressions in CRF rats.Selisistat(a SIRT1 inhibitor)mitigates the changes in SIRT1,p-AMPK,p-ULK1,p-mTOR,and LC3B expressions induced by aminophylline.Finally,RAPA alleviates renal injury and apoptosis in CRF rats,and 3-MA eliminates the aminophylline-induced inhibition of renal injury and apoptosis in CRF rats.Aminophylline suppresses chronic renal failure progression by modulating the SIRT1/AMPK/mTOR-mediated autophagy process.

关 键 词：chronic renal failure aminophyline SIRT1 MTOR AUTOPHAGY 

分 类 号：R692.5[医药卫生—泌尿科学]