Effects and mechanisms of cholecystokinin octapeptide on hippocampal injury during endotoxic shock / 中国应用生理学杂志

<p><b>AIM</b>To study the effects and the mechanisms of cholecystokinin octapeptide(CCK-8) on hippocampal injury during endotoxic shock (ES).</p><p><b>METHODS</b>Rabbits 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.</p><p><b>RESULTS</b>LPS 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.</p><p><b>CONCLUSION</b>CCK-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.</p>

Effects of cholecystokinin-octapeptide on the tension of pulmonary artery in rabbits with endotoxic shock / 生理学报

For investigation of the regulatory mechanism of cholecystokinin-octapeptide (CCK-8) on pulmonary circulation in rabbits with endotoxic shock (ES) induced by lipopolysaccharides (LPS), mean arterial pressure (MAP) and pulmonary arterial pressure (PAP) were evaluated for 5 h in five groups of rabbits: group of LPS (8 mg/kg, i.v.)-induced ES, group of CCK-8 pretreatment (15 microg/kg, i.v.) 15 min before LPS administration (8 mg/kg, i.v.), group of proglumide pretreatment (1 mg/kg, i.v.) 15 min before LPS administration (8 mg/kg, i.v.), group of CCK (15 microg/kg, i.v.) only, and normal saline (control) group. The pulmonary arterial tension was measured with isolated vascular ring technique. The results showed that LPS-induced pulmonary arterial hypertension was abolished by CCK-8. In contrast, proglumide, a nonspecific antagonist of CCK-8 receptor, potentiated the deleterious effect of LPS. The contractile response of isolated pulmonary artery to alpha-adrenoceptor agonist phenylephrine (PE) was enhanced and the relaxation response to acetylcholine (ACh) was depressed significantly after LPS was injected, but the effect could be reversed by CCK-8. These results suggest that pulmonary circulation is improved by CCK-8 in ES, and the regulatory effects of CCK-8 may be brought about by modulating the pulmonary arterial tension.