八肽胆囊收缩素对脂多糖诱导肺动脉内皮细胞凋亡的抑制作用

目的：探讨八肽胆囊收缩素（CCK－8）对脂多糖（LPS）诱导培养的肺动脉内皮细胞（BPAEC）凋亡的影响。方法：培养的BPAEC用LPS、CCK－8、CCK－8非特异性受体阻断剂丙谷胺分别或共同处理后，继续培养24小时。用流式细胞术和核荧光染色方法检测细胞凋亡，用生物化学方法检测培养上清中乳酸脱氢酶（LDH）活性和丙二醛（MDA）含量，用流式细胞术定量检测过氧亚硝基阴离子（ONOO^-)含量。结果：LPS可诱导BPAEC凋亡和坏死明显增多，培养上清中MDA含量增高；CCK－8抑制BPAEC凋亡和MDA含量的增高，此作用为CCK－8受体非特异性阻断剂丙谷胺翻转；CCK－8可抑制LPS诱导BPAEC生成ONOO^-增多；CCK－8和丙谷胺对LPS诱导的BPAEC坏死无明显影响。结论：CCK－8可抑制LPS诱导的BPAEC凋亡，此作用由其受体介导，并与CCK－8的抗氧化功能有关。

Inhibitory effect of cholecystokinin octapeptide on lipopolysaccharideinduced apoptosis of pulmonary artery endothelial cells

Objective:To investigate the effect of cholecystokinin octapeptide (CCK8) on lipopolysaccharide (LPS)induced apoptosis of cultured pulmonary artery endothelial cells (BPAEC).Methods:BPAEC were challenged with LPS,CCK8,proglumide and vehicle,respectively.Then the cells continued to be cultured for 24 hours.The cellular apoptosis was analyzed by flow cytometer and fluorecent stain,and the content of malondialdehyde (MDA) and lactate dehydrogenase(LDH) activity were measured by biochemical methods.The cellular necrosis was expressed by LDH activity in supernatant.The endothelialderived peroxynitrite (ONOO -),a strong oxidant resulted from the reaction of nitric oxide and superoxide,was measured by the assay of ONOO - marker molecule nitrotyrosine (NT) with flow cytometer.Results:LPS could significantly induce increased apoptosis and necrosis in BPAEC,and elevate MDA contents in supernatant.CCK8 reversed LPSinduced increase in apoptosis and MDA contents,however these effects were abolished by proglumide,a nonspecific antagonist of CCK8 receptors.In contrast,CCK8 and proglumide had minimal effect on LPSinduced LDH activity,indicating that there was no significant change of necrosis in BPAEC.CCK8 inhibited LPSinduced ONOO - generation in BPAEC.Conclusions:LPSinduced apoptosis of BPAEC could be inhibited by CCK8,and it might be mediated by its receptors.Antioxidation activity of CCK8 might also play a role.