Propofol combined with hypoxia induces cognitive dysfunction in immature rats via p38 pathway

Abstract

To investigate the effects of propofol combined with hypoxia on cognitive function of immature rats and the possible role of p38 pathway and tau protein in mediating such effects. Ninety 7-day-old (P7) SD rats were randomized for daily intraperitoneal injection of propofol (50 mg/kg) or lipid emulsion (5.0 mL/kg) for 7 consecutive days. After each injection, the rats were placed in a warm box (38 ℃) with an oxygen concentration of 18% (hypoxia), 21% (normal air), or 50% (oxygen) until full recovery of the righting reflex. Another 90 P7 rats were similarly grouped and received intraperitoneal injections of p-p38 blocker (15 mg/kg) 30 min before the same treaments. The phosphorylated tau protein, total tau protein and p-p38 content in the hippocampus were detected using Western blotting. The spatial learning and memory abilities of the rats were evaluated with Morris water maze test. Compared with lipid emulsion, propofol injection resulted in significantly increased levels of p-p38, phosphorylated tau and total tau proteins in rats with subsequent hypoxic or normal air treatment (P < 0.05), but propofol with oxygen and injections of the blocker before propofol did not cause significant changes in the proteins. Without subsequent oxygenation, the rats receiving injections of propofol, with and without prior blocker injection, all showed significantly prolonged latency time and reduced platform-crossing times and third quadrant residence time compared with the corresponding lipid emulsion groups (P < 0.05). With oxygen treatment, the rats in propofoland blocker-treated groups showed no significant difference in the performance in Morris water maze test from the corresponding lipid emulsion group. The results of Morris water maze test differed significantly between blocker-propofol group and propofol groups irrespective of exposures to different oxygen levels (P < 0.05), but not between the lipid emulsion and blocker group pairs with exposures to different oxygen levels. Propofol combined with hypoxia can affect the expression of tau protein through p38 pathway to impair the cognitive function of immature rats, in which oxygen plays a protective role.