Protective effects of penehyclidine hydrochloride on lipopolysaccharide-induced endothelial cells injury / 中华急诊医学杂志

ABSTRACT

Objective To investigate the effects of penehyclidine hydrochloride ( PHC) on lipopolysaccharide (LPS) -induced endothelial cells injury and its mechanism. Methods ECV-304 was cultured in RPMI1640 in a 5% humidified CO2 atmosphere at 37 ℃. Then cultured cells were used to assess the following treatments control group, LPS group (1 μg/mL) and PHC group(2 μg/mL). At the end of the experiments, supernatant was collected for determination of lactate dehydrogenase ( LDH), and cells were collected for determination of malondialdehyde (MDA), superoxide dismutase (SOD), and nitric oxide (NO) levels. And extracellular regulated kinasel/2( ERKl/2)and JNK MAPK (mitogen-activated protein kinases, MAPK) protein expressions were determined using Western blot technique. Analysis of variance (ANOVA) was used for statistical analysis to compare values among all groups. A significant difference was presumed for a probability value < 0.05. Results Compared with control group, LDH leakage [(1642 ± 367) U/L vs (169±33)U/L], the contents of MDA[(13. 2 ± 1. 2) nmol/L vs (7. 2 ±0. 8)nmol/mL] and NO levels [(143.2 ± 10.3) μmol/L vs(85.5 ±4.1) μmol/L], expressions of ERK1/2 and JNK were remarkably increased and SOD activities[(41.2 ±2.7) U/mL vs (61. 1 ±2.8) U/mL] were obviously decreased in LPS group. PHC markedly decreased LDH leakage [(392 ±90) U/L], MDA contents [(8. 6 ± 1. 3) nmol/ mL] and NO levels [(92.1 ±6.6) μmol/L], ERK1/2 activation and enhanced SOD activities [(58.0± 3.0) U/mL]. Conclusions PHC could protect endothelial cells against LPS-induced cell injury. The effect of PHC is likely mediated through inhibition of ERK1/2 MAPK activation.