title: Receptor-interacting protein kinase 3-mediated programmed cell necrosis in rats subjected to focal cerebral ischemia-reperfusion injury.
abstract: In the current study, the activation of tumor necrosis factor-α receptor 1 (TNFR1) and receptor-interacting protein kinase 3 (RIP3) were investigated following cerebral ischemia-reperfusion injury (CIRI). Healthy SD rats were randomly divided into 3 groups: Sham operation group, model group and inhibitor group. The model group and inhibitor group were further divided into 4 subgroups of 6, 12, 24 and 72 h following CIRI. Using right middle cerebral artery embolization, the CIRI model was generated. To confirm that the CIRI model was established, neurological scores, TTC staining and brain water content measurements were conducted. Immunohistochemistry and western blotting were conducted to investigate the expression of TNFR1 and RIP3 in the cerebral cortex. It was observed that nerve cell necrosis occurred following 6 h of CIRI. The appearance of necrotic cells was gradually increased with increasing CIRI duration. TNFR1 and RIP3 were positively expressed following 6 h of CIRI. With increasing durations of CIRI, the protein expression levels of TNFR1 and RIP3 were significantly increased. Pre‑administration with Z-VAD-FMK (zVAD) significantly increased the protein level of RIP3, however, had no effect on the levels of TNFR1, and was accompanied by a reduction in necrosis. In conclusion, RIP3‑mediated cell necrosis was enhanced by caspase blockade zVAD and the function of zVAD was independent of TNFR1 signaling following IR.
authors.affiliation: Department of Histology and Embryology, Liaoning Medical University, Jinzhou, Liaoning 121001, P.R. China.
authors.forename: Yanru
authors.initials: Y
authors.lastname: Dong
authors.affiliation: Key Laboratory of Molecular Cell Biology and New Drug Development, Liaoning Medical University, Jinzhou, Liaoning 121001, P.R. China.
authors.forename: Cuifen
authors.initials: C
authors.lastname: Bao
authors.affiliation: Department of Histology and Embryology, Liaoning Medical University, Jinzhou, Liaoning 121001, P.R. China.
authors.forename: Jingwei
authors.initials: J
authors.lastname: Yu
authors.affiliation: Department of Histology and Embryology, Liaoning Medical University, Jinzhou, Liaoning 121001, P.R. China.
authors.forename: Xia
authors.initials: X
authors.lastname: Liu
mesh_terms: D000818:Animals; D017209:Apoptosis; D020520:Brain Infarction / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D002545:Brain Ischemia / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D061945:Caspase Inhibitors / Q000008:administration & dosage; D020169:Caspases / Q000378:metabolism; D004195:Disease Models, Animal; D015870:Gene Expression; D008297:Male; D009336:Necrosis; D009842:Oligopeptides / Q000008:administration & dosage; D051381:Rats; D053422:Receptor-Interacting Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism*; D047888:Receptors, Tumor Necrosis Factor, Type I / Q000235:genetics / Q000378:metabolism; D015427:Reperfusion Injury / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*
chemical_list: D061945:Caspase Inhibitors; D009842:Oligopeptides; D047888:Receptors, Tumor Necrosis Factor, Type I; C517629:benzyloxycarbonyl-valyl-alanyl-aspartic acid; D053422:Receptor-Interacting Protein Serine-Threonine Kinases; C582791:Ripk3 protein, rat; D020169:Caspases