Effect of necrostatin-1 pre-treatment on postoperative cognitive function in aged rats with chronic pain due to knee arthritis / 中华麻醉学杂志

ABSTRACT

Objective:To evaluate the effect of necrostatin-1 (Nec-1)pre-treatment on postoperative cognitive function in aged rats with chronic pain due to knee arthritis.Methods:One hundred and twenty healthy male Sprague-Dawley rats, aged 22 months, weighing 550-600 g, were divided into 4 groups ( n=30 each) using a random number table method: chronic pain due to knee arthritis group(group P), chronic pain due to knee arthritis + operation group (group PS), dimethyl sulfoxide (DMSO) + chronic pain due to knee arthritis + operation group (DMSO+ PS group), and necrostatin-1 + chronic pain due to knee arthritis + operation group (Nec-1+ PS group). The inflammation-induced knee arthritis model was developed by injecting monosodium iodoacetate (MIA) into the left joint cavity.The exploratory laparotomy under sevoflurane anesthesia was performed at 12 weeks after intra-articular MIA injection. In Nec-1+ PS group and DMSO+ PS group, necrosstatin-1 6.25 mg/kg and the equal dose of DMSO were intraperitoneally injected at 1 h before surgery, respectively. At 7 days after surgery, the Morris water maze test was used to evaluate the cognitive function, the activation of microglial cells in the dentate gyrus of hippocampus was observed by immunofluorescent staining, and the activation rate of microglia cells was calculated, the necrosis rate of neurons was determined by flow cytometry, the expression of receptor-interacting protein kinase 1 (RIPK1)and phosphorylated mixed lineage kinase domain-like protein (p-MLKL) was determined by Western blot, and the contents of tumor necrosis factor-alpha (TNF-α), interleukin-1beta (IL-1β) and IL-6 were determined by enzyme-linked immunosorbent assay. Results:Compared with P group, the escape latency was significantly prolonged, the time of staying at the original platform quadrant was shortened, and the number of crossing the original platform was reduced, the activation rate of microglia cells in the hippocampal dentate gyrus and necrosis rate of hippocampal neurons were increased, the expression of RIPK1 and p-MLKL was up-regulated, and the contents of pro-inflammatory factors TNF-α, IL-1β and IL-6 in hippocampus were increased in PS, DMSO+ PS and Nec-1+ PS groups ( P<0.05). Compared with PS group and DMSO+ PS group, the escape latency was significantly shortened, the time of staying at the original platform quadrant was prolonged, and the number of crossing the original platform was increased, the activation rate of microglia cells in the hippocampal dentate gyrus and necrosis rate of hippocampal neurons were decreased, the expression of RIPK1 and p-MLKL was down-regulated, and the contents of pro-inflammatory factors TNF-α, IL-1β and IL-6 in hippocampus were decreased in Nec-1+ PS group ( P<0.05). Conclusions:Necrostatin-1 pre-treatment can improve postoperative cognitive function in aged rats with chronic pain due to knee arthritis, and the mechanism may be related to inhibition of necrosis in hippocampal neurons and reduction of neuroinflammation.