κ-opioid receptor activation inhibits endothelial injury induced by sodium palmitate via caveolin-eNOS pathway

AIM To investigate the effect of κ-opioid receptor activation on sodium palmitate (SP)-induced human umbilical vein endothelial cells (HUVECs) injury and the underlying mechanism. METHODS HUVECs were divided into 6 groups: control group, U50,488H group (a selective κ-opioid receptor agonist), SP group, SP+U50,488H group, SP+U50,488H+nor-BNI (a selective κ-opioid receptor antagonist) group and SP+U50,488H+L-NAME (an eNOS inhibitor). Caveolin-1 and eNOS protein expressions were detected by Western blot, respectively. Cell survival rate was assayed by cell counting kit (CCK-8), apoptotic cells were determined by flow cytometry and NO production was analyzed by nitric oxide assay kit. RESULTS Compared with the control group, SP group showed a lower cell survival rate (P<0.01), significantly higher caveolin-1 protein expression (P<0.01), impaired eNOS activity (P<0.05), reduced NO production (P<0.01) and increased cell apoptosis (P<0.01). SP-induced HUVECs injury was ameliorated by U50,488H, as evidenced by a higher cell survival rate (P<0.01), reduced caveolin-1 protein expression (P<0.01), restored eNOS expression (P<0.05), increased NO production (P<0.01) and lower cell apoptosis (P<0.01). The protective effect of U50,488H against SP-induced HUVECs injury was abolished by nor-BNI or L-NAME. CONCLUSION κ-opioid receptor activation protects HUVECs against SP-induced injury by down-regulation of caveolin-1 and up-regulation of eNOS activity.