AIMTo study the effects and the mechanisms of cholecystokinin octapeptide(CCK-8) on hippocampal injury during endotoxic shock (ES).

METHODSRabbits were injected intravenously with lipopolysaccharide (LPS, 8 mg/kg) to establish ES model. Thirty-two Rabbits were divided into 4 groups at random (n = 8): control (saline, iv), LPS, CCK-8 + LPS (CCK-8 pre-administrated 30 min before LPS, iv), proglumide (Pro, nonspecific antagonist of CCK receptors) + LPS (Pro pre-administrated 30 min before LPS, iv) group. The changes of mean arterial pressure (MAP) were measured. The morphologic changes in the hippocampus were observed through light microscope (LM) and transmission electron microscope (TEM). The alterations of activities of nitric oxide synthase (NOS) and superoxide dismutase (SOD), contents of nitric oxide (NO) and malondialdehyde (MDA) in the hippocampus were assayed. Twelve Sprague-Dawley rats, grouped as that of the rabbits, were used to detect the expression of inducible NOS (iNOS) and neuronal NOS (nNOS) protein by immunohistochemistry staining.

RESULTSLPS administration resulted insignificant reduction in MAP (P < 0.01 vs control group) and hydropic degeneration of neurons in the hippocampus. Compared with those of control group, the NOS activity, NO level and MDA content were increased significantly (P < 0.05, P < 0.01 and P < 0.05), while SOD activity was reduced (P < 0.01) in the hippocampus of ES rabbits. LPS administration induced the expression of iNOS protein in the cytoplasm of hippocampus neurons, and lead to stronger positive signals of nNOS than that of control group. CCK-8 pre-administration could alleviate the changes induced by LPS, while Pro pre-administration aggravated those alterations.

CONCLUSIONCCK-8 could protect hippocampus neurons against the injury induced by LPS during ES, which might be associated with its effects of suppressing the over production of NO and free radicals.