Abstract: Abstract: Objective To study the relationship between receptor interacting protein (RIP)1 and hepatocyte necroptosis in isoniazid (INH) induced mouse model. Methods Kunming male mice were randomly divided into three groups. Control group (C) received 0.3 mL of normal saline one time per day. INH group (INH) was injected intraperitoneally INH 100 mg/kg body weight, one time per day. Nec-1 + INH group was injected intraperitoneally Nec-1 in 0.1% DMSO and 1 mg/kg body weight one time/12 hours, and INH was injected intraperitoneally at the same dose with that of INH group. All animals were treated for 7 days. Pathological changes of liver tissues were studied by HE staining. RIP1 expression was detected by immunohistochemical, Western blot and real-time PCR analysis. Levels of malondialdehyde (MDA), reactive oxygen species(ROS), glutathione (GSH) and superoxide dismutase (SOD) in liver homogenate were determined by colorimetric method. Results Hepatocytes were arranged orderly in C group. The degeneration and necrosis of hepatocytes were found in Nec-1+INH group, and severe degeneration and necrosis of hepatocytes were found in INH group. Compared with C group, the expression levels of RIP1, ROS and MDA were increased significantly, and the expression levels of GSH and SOD were decreased significantly in INH group (P＜0.05). INH-induced acute liver necroptosis was significantly alleviated after treatment with Nec-1. Compared with INH group, the expression levels of RIP1, MDA and ROS were significantly decreased, and the expression levels of GSH and SOD were significantly increased in Nec-1+INH group (P＜0.05). Conclusion These results suggest that RIP1 is involved in INH-induced hepatocyte necroptosis in mice. The inhibition of RIP1 expression might be a treatment strategy for prohibition of INH-induced acute liver necroptosis.

Key words: isoniazid, hepatocyte, necroptosis, receptor interacting protein1