Irbesartan Lysophospholipids Induced Vascular Endothelial Injury In Clinical And Basic Research

To explore the effects of Irbesartan on the plasma concertrations of lysophosphatidic acid(LPA), endothelin-1(ET-1), serum concertration of NO and its clinical efficacy in the patients with acute cerebral infarction. Methods All of the 53 patients were randomly assigned to Irbesartan therapy group(n=25) treated with Irbesartan 150mg/d+Aspirin 100mg/d and conventional therapy group(n=28) treated with Aspirin100mg/d. Both groups were treated for 14 days and the other measures of symptomatic therepy were the same. And another 30 persons without cerebrovascular diseases were taken as control group. The venous blood samples were taken for measureing the levels of LPA, ET-1, NO, while the scorces of neurological deficit(NDS) were evaluated before and after treatment.Results (1) Before treatment the levels of LPA, ET-1 in cerebral infarction (CI) group were significantly higher and the level of NO was significantly lower than that in control group (p＜0.05) and the NDS was negatively related with the NO expression in CI group( partial correlation coefficient=-0.4345, p＜0.05). (2)After treatment the levels ofLPA, ET-1, NDS were significantly lower and the level of NO was significantly higher than that before treatment in both CI groups p＜0.05). (3) Compared with the conventional therapy group the indexs of LPA, ET-1, NO were improved more significantly in Irbesartan therapy group (p＜0.05). Conclusion Irbesartan further decreased the levels of LPA, ET-1 and increase the level of NO, which implies the role of Irbesartan on inhibiting platelet activation and endothelial protection in the patients with acute cerebral infarction. To investigate the protective effects of irbesartan on cultured human umbilical vein endothelial cells (HUVECs) impaired by lysophosphatidylcholine(LPC). Methods HUVECs were cultured in vitro. The study was designated to 8 groups: (1)normal c ontro1, (2)low-concentration LPC group(10μg/L), (3)middle-concentration LPC group(20μg/L), (4)high-concentration LPC group (40μg/L), (5)Irb control group containing LPC(20μg/L), (6)low-concentration Irb group(10^-7μmol/L), (7)middle-concentration Irb group(10^-6μmol/L), (8)high-concentration Irb group(10^-5μmol/L). All of the groups were cultured for 24h and the groups of (6)～(8) were cultured with Irb for 2h before cultured with LPC(20μg/L) for 24h. The concentration of angiotensinⅡ(AngⅡ), mRNA expressions of AngⅡtypel receptor(AT1R) and AngⅡtype2 receptor(AT2R) were observed by radio-immunity and rt-PCR respectively. Production of nitrogen monoxidum(NO), activity of nitricoxide synthase(NOS) and superoxide dismutase(SOD) were determined by chromatometry. Also the intervention effects of Irb were observed. Results Compared with nomal control group, LPC could up-regulate the expression of AngⅡand AT₁RmRNA, and decrease the expression of NO and the activity of NOS, SOD significantly in a concentration depended manner (p＜0.05); Irb could significantly increase the expression of NO and the activity of NOS, SOD (p＜0.05). Conclusion Irb might play a protective role on the HUVECs impaired by LPC.