Protective roles of cholecystokinin in endotoxin-induced and peroxynitrite-mediated injury in pulmonary artery endothelial cells
- Author:
Zhenyong GU
;
Yiling LING
- Publication Type:Journal Article
- From:
Chinese Journal of Pathophysiology
2001;17(8):772-
- CountryChina
- Language:Chinese
-
Abstract:
Our previous experiments confirmed that endothelial derived ONOO- mediated injury to cultured BPAEC induced by LPS, and that CCK protected endothelial functions against the detrimental effect of LPS in vitro. In the present study, using cultured BPAEC, we investigated effect of CCK on LPS-induced generation of ONOO- in BPAEC and on injury to BPAEC induced by LPS. Results were as follows.(1)CCK inhibited increase in endothelial generation of ONOO- induced by LPS, for fluorescent intensity of NT in BPAEC reduced from (6.55±0.30) AU of LPS group to (4.37±0.08) AU (P＜0.01), the latter being still higher than (3.27±0.15) AU of vehicle group (P＜0.01). In contrast, the number and percentage of NT positive cells reduced a little. Proglumide, a nonspecific inhibitor of CCK receptors, might in part reverse the effect of CCK. (2)CCK markedly reduced MDA content in supernatant in LPS group (P＜0.01), which was completely reversed by proglumide(P＜0.01). Activities of LDH in supernatant in LPS, LPS+CCK group were (85.30±8.66) U/L and (71.33±4.07) U/L, respectively. Proglumide elicited increase in activity of LDH ［(81.00±6.35) U/L］. However, effect of CCK or proglumide was not significant in the alterations of activity of LDH. (3)CCK significantly inhibited increase in apoptotic rate in BPAEC induced by LPS, from 13.50%±0.60% of LPS group to 5.35%±0.25%(P＜0.001), the latter being completely reversed by proglumide with apoptotic rate of 11.45%±0.65%(P＜0.05).These results further confirmed that CCK afforded the cyoprotection for the mitigation lipoperoxide damage and inhibition of apoptosis in BPAEC induced by LPS. The cytoprotection of CCK may be mediated by CCK receptors and related to the reductive ability of endothelia to generate ONOO- induced by LPS.
