Effects of κ opioid receptor agonist on cognitive function and expression of p-tau and Aβ in hippocampus of rats undergoing cardiopulmonary bypass

Objective To investigate the effect of κ opioid receptors (KORs) on cognitive function and the expression of p-tau and Aβ in hippocampus of rats after cardiopulmonary bypass(CPB).

Methods A total of 40 clean grade adult male SD rats were randomly divided into four groups: sham operation group (n=10, group S), CPB group (n=10, group C), CPB+KORs agonists U50488H group (n=10, group U), CP B+KORs antagonist Nor-BNI+U50488H group (n=10, group N). Before operation, rats in each group were given water maze training for 5 days, four times a day. In group S, only arteriovenous catheterization was performed without CPB. In group C, arteriovenous catheterization was performed with CPB for 1 hour. In group U, U5-0488H for 1.5 mg/kg was intravenously injected 30 minutes before CPB, and the rest performance was the same to group C. In group N, Nor-BNI for 2 mg/kg was intravenously injected 1 hour before CPB, and the rest performance was the same as in group U. On the 3rd day of operation after the water maze training, rats were killed by bloodletting and hippocampus tissue was taken off. Enzyme-linked immunosorbent assay (ELISA) was used to detect the content of Aβ. Western blot was used to detect the expression of p-tau.

Results Compared with the group S, the escape latency of rats in the other three groups was prolonged, the number of crossing platform, swimming distance and stay time in target quadrant were significantly reduced, the expression of p-tau protein and the content of Aβ protein in hippocampus were significantly increased (P < 0.05); compared with the group C, the escape latency of rats in the group U was significantly shortened, the number of crossing platform and swimming distance in target quadrant were significantly increased, the stay time was longer, and the expression of p-tau and the content of Aβ decreased (P < 0.05), while there were no significant differences in above indicators between group N and group C (P>0.05).

Conclusion KORs agonists can reduce the expression of p-tau and Aβ proteins in hippocampal tissue, and may thus play a protective role in cognitive function of rats after CPB.