Rapamycin improves renal injury induced by Iodixanol in diabetic rats by deactivating the mTOR/p70S6K signaling pathway

• DOI: 10.1016/j.lfs.2020.118284
• Publication Date: 2020-08-14T01:21:57Z
• Authors: Yan Wang; Haoyu Zhang; Tianshu Pang; Zhongfu Zuo; Ke Ren
• Keywords: Male; Sirolimus; 0301 basic medicine; TOR Serine-Threonine Kinases; Ribosomal Protein S6 Kinases, 70-kDa; Apoptosis; Acute Kidney Injury; Kidney; Streptozocin; Diabetes Mellitus, Experimental; Rats; 3. Good health; Rats, Sprague-Dawley; 03 medical and health sciences; Triiodobenzoic Acids; Autophagy; Animals; Phosphorylation; Signal Transduction

To study how to effectively prevent or reduce renal injury caused by contrast agents in diabetic patients.Sprague Dawley (SD) rats were bred with a high-fat diet for eight weeks, then intraperitoneally injected with Streptozotocin (STZ) to prepare the diabetes model. Rats were treated with Iodixanol to prepare a contrast-induced acute kidney injury (CIAKI) model. Moreover, 3-methyladenine (3-MA), an autophagy inhibitor, was administrated to diabetic rats with or without Rapamycin treatment. Serum creatinine (SCr) and blood urea nitrogen (BUN) were examined using Biochemical detector. Kidney injury molecule-1 (KIM-1), N-acetyl-β-D-amino glycosidase (NAG) in urine, inflammatory and oxidative stress factors in serum were determined by ELISA. The expression level of ROS was quantified by immunofluorescence (IF). The protein expressions of Bax, BCl-2, LC3, Beclin1, mTOR and p70S6K in renal tissue were detected by Western blot.Rapamycin was demonstrated to improve renal injury induced by Iodixanol diabetic rats, decrease the levels of SCr, BUN, KIM-1, NAG, improve renal functions, reduce inflammatory response and oxidative stress injury, down-regulate Bax, while up-regulate BCl-2 and inhibit apoptosis. Moreover, Rapamycin could inhibit the phosphorylation of mTOR/p70S6K pathway-associated proteins, activate autophagy and increase the levels of LC3 and Beclin1. After treatment with 3MA, an inhibitor of mTOR/p70S6K signaling pathway, the protective effects of Rapamycin on CIAKI were weakened.Rapamycin can alleviate renal injury induced by Iodixanol diabetic rats, and its regulatory mechanisms may be related to the regulation of mTOR/p70S6K signaling pathway and the activating autophagy.