Protective mechanism of necrostatin-1 on acute tubular necrosis in rats

Abstract

Objective To observe the protective effect of Necrostatin-1 on acute tubular necrosis (ATN) rats, and to analyze the mechanism. Methods Forty-five SD male rats were enrolled to prepare ATN aninal model by intramuscular injection of glycerol production, and they were randomly divided into model group, low dose group and high dose group, with 15 rats in each group. Fifteen normal rats were selected as control group. Rats in low dose group and high dose group were given 0.4 mg/kg and 0.8 mg/kg Nec-1 (dissolved in DMSO) by tail vein. Rats in model group and control group were injected with equal DMSO. Serum creatinine (Scr), blood urea nitrogen (BUN) and renal failure index (RFI) were analyzed. Tumor necrosis factor alpha (TNF-α) and interleukin-1β (IL-1β) levels in peripheral blood were detected by ELISA method. Receptor interacting protein 1 (RIP1) and receptor interacting protein 3(RIP3) were detected by Western blot. Pathological changes of kidney were observed and analyzed by HE stain. Results Compared with control group, Scr level, BUN level and RFI of rats in model group, low dose group and high dose group were increased significantly (P<0.05), TNF-α, IL-1β, RIP1 and RIP3 levels in kidney tissues of rats were increased significantly (P<0.05). Compared with model group, Scr level, BUN level and RFI of rats in low dose group and high dose group were decreased significantly (P<0.05), TNF-α, IL-1β, RIP1 and RIP3 levels in kidney tissues of rats were decreased significantly (P<0.05). Compared with control group, pathological results showed that the kidney grew in varying degrees, renal tubular deformed obviously, protein tube type in lumen increased in model group, low dose group and high dose group. The pathological change of rats in model group were more significant than that of low dose group and high dose group (P<0.05). The changes of each index of the low dose and high dose group were dose dependent. Conclusions Necrostatin-1 can effectively improve Scr, BUN level and RFI of rats with acute renal tubular necrosis. It plays a role in protecting the kidney with the mechanism of the inhibition of the levels of inflammatory factors and programmed cell necrosis. Key words: Necrostatin-1; Acute tubular necrosis; Serum creatinine; Blood urea nitragen; Renal function index; Inflammatory factors