八肽胆囊收缩素对内毒素休克时海马损伤的影响及其机制初探

目的：观察八肽胆囊收缩素（CCK-8）对内毒素休克（ES）时海马损伤的影响,并探讨其可能的作用机制。方法：将日本大耳白兔经静脉注入内毒素的主要活性成分脂多糖（LPS,8mg／kg）复制ES模型。动物（32只）随机分为对照组、LPS组、CCK-8＋LPS组和非特异性CCK受体拮抗剂丙谷胺（Pro）＋LPS组（n=8）。监测平均动脉压（MAP）的变化,光、电镜观察海马的组织形态学改变,比色法检测海马NOS和SOD活性、N0和MDA含量的改变．用SD大鼠（12只,同上复制模型及分组）以免疫组织化学染色法观察海马iNOS和nNOS表达的变化。结果：与对照组相比,注入LPS后出现MAP显著而持续下降（P〈0．01）;海马部位神经元损伤明显;iNOS和nNOS表达增强,NOS活性、NO和MDA含量显著升高（P〈0．05、P〈0．01和P〈0．01）,SOD活性则降低（P〈0．01）。预先注入CCK-8可明显减轻上述变化,预先注入Pro则加剧以上变化。结论：CCK-8可减轻ES时脑内海马部位的损伤。其机制可能与其抗氧化作用和抑制NO的过量生成有关。

Effects and mechanisms of cholecystokinin octapeptide on hippocampal injury during endotoxic shock

Aim: To study the effects and the mechanisms of cholecystokinin octapeptide(CCK-8) on hippocampal injury during endotoxic shock(ES).Methods: Rabbits were injected intravenously with lipopolysaccharide(LPS,8mg/kg) to establish ES model.Thirty-two Rabbits were divided into 4 groups at random(n=8): control(saline,iv),LPS,CCK-8+LPS(CCK-8 pre-administrated 30 min before LPS,iv),proglumide(Pro,nonspecific antagonist of CCK receptors)+LPS(Pro pre-administrated 30 min before LPS,iv) group.The changes of mean arterial pressure(MAP) were measured.The morphologic changes in the hippocampus were observed through light microscope(LM) and transmission electron microscope(TEM).The alterations of activities of nitric oxide synthase(NOS) and superoxide dismutase(SOD),contents of nitric oxide(NO) and malondialdehyde(MDA) in the hippocampus were assayed.Twelve Sprague-Dawley rats,grouped as that of the rabbits,were used to detect the expression of inducible NOS(iNOS) and neuronal NOS(nNOS) protein by immunohistochemistry staining.Results: LPS administration resulted insignificant reduction in MAP(P<0.01 vs control group) and hydropic degeneration of neurons in the hippocampus. Compared with those of control group,the NOS activity,NO level and MDA content were increased significantly(P<0.05,P<0.01 and P<0.05),while SOD activity was reduced(P<0.01) in the hippocampus of ES rabbits. LPS administration induced the expression of iNOS protein in the cytoplasm of hippocampus neurons,and lead to stronger positive signals of nNOS than that of control group.CCK-8 pre-administration could alleviate the changes induced by LPS,while Pro pre-administration aggravated those alterations.Conclusion: CCK-8 could protect hippocampus neurons against the injury induced by LPS during ES,which might be associated with its effects of suppressing the over production of NO and free radicals.