Ept Protects Against Low-Density Lipoprotein-Induced Endothelial Dysfunction

Objective: The protective effects of extractive of pericarpium trichosanthis (EPT)on vascular endothelial cells of rat and human umbilical vein were studied, and low density lipoprotein (LDL) or oxide low-density lipoprotein (ox-LDL) was used to damage vascular endothelium or endothelial cells. The endogenous related substances in blood plasma or cell culture medium were detected to prove that EPT has protective effect on vascular endothelium damaged by LDL.Methods: 1) Aortic ring model: the endoehilal injuried aortic ring was maded by a single dose of LDL (4 mg/kg) intravenously injected into the sublingual vein of male rat for 48 h, and physiological saline injection served as a control. Blood samples were collected from carotid artery in the state of anaesthetization. Vasodilator responses to acetylcholine (Ach) in the isolated aortic rings were determined, and serum concentrations of asymmetric dimethylarginine (ADMA), malondialdehyde (MDA), tumour necrosis factor-alpha (TNF-alpha), Nitric oxide (NO). 2) Cell culture and treatment: Incubation human umbilical vein endothelial cells (HUVECs) with ox-LDL (100 mu g/ml) for 24h, the medium levels of lactate dehydrogenase (LDH), ADMA, TNF-alpha, NO, MDA and the intracellular activity of DDAH were measured.Results: A single injection of LDL (4 mg/kg) significantly decreased vasodilator responses to Ach, increased the serum level of ADMA, MDA and TNF-alpha, and decreased the serum level of NO. EPT (4ml/kg) with 70% ethanol elution markedly reduced the inhibition of vasodilator responses to Ach by LDL, and the protective effect of EPT with 70% ethanol elution was greater compared with the another ethanol elution group. EPT with 70% ethanol elution inhibited the increased level of ADMA, MDA and TNF-alpha induced by LDL, and increased the serum level of NO. Incubation of HUVECs with ox-LDL (100 mu g/ml) for 24h and treated with EPT (0.1mg/ml) markedly decreased the medium levels of LDH, ADMA, MDA and TNF-alpha, and increased the level of NO in the medium and the intracellular activity of DDAH.Conclusions: EPT can protect the endothelium against damages elicited by LDL in vivo and in culture, the mechanism of protective effect of EPT on endothelium may be related to the DDAH/ADMA pathway.