八肽胆囊收缩素对内毒素休克时大脑皮质损伤的影响及其机制初探

Effects of cholecystokinin octapeptide on cerebral cortex injury during endotoxic shock

目的观察八肽胆囊收缩素(CCK-8)对内毒素休克(ES)时大脑皮质损伤的影响,并探讨其可能的机制。方法将日本大耳白兔经静脉注入脂多糖(LPS,8mg/kg)复制ES模型。32只家兔随机分为对照组、LPS组、CCK-8+LPS组和非特异性CCK受体拮抗剂丙谷胺(Pro)+LPS组,每组8只。监测平均动脉压(MAP)变化,光、电镜观察大脑皮质的组织形态学改变,比色法检测大脑皮质NOS和SOD活性、NO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大脑皮质iNOS和nNOS表达的变化。结果注入LPS后,MAP明显持续低于对照组(P<0.01),大脑皮质组织水肿,iNOS和nNOS表达增强,NOS活性、NO和MDA含量显著高于对照组(P<0.05、P<0.01和P<0.01),SOD活性显著低于对照组(P<0.01)。预先注入CCK-8可明显减轻上述变化,预先注入丙谷胺Pro则加剧以上变化。结论CCK-8可减轻ES时的大脑皮质损伤,其机制可能与其抗氧化作用和抑制NO的过量生成有关。

AIM： To study the effects of cholecystokinin octapeptide （CCK- 8） on cerebral cortex injury during endotoxic shock （ES） and its mechanisms. METHODS： Rabbits were injected intravenously with lipopolysaccharide （LPS, 8 mg/kg） to establish ES model. Rabbits （ n = 32, 8 in each group） were randomly assigned to receive one of four treatments intravenously： normal saline （as control）, LPS, CCK- 8 pretreatment 30 min before LPS, proglumide （Pro, nonspecific antagonist of CCK receptors） pretreatment 30 min before LPS. The changes of mean arterial pressure （MAP） were measured. The morphologic changes in cerebral cortex 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 cerebral cortex were assayed. The expressions of protein of inducible NOS （iNOS） and neuronal NOS （nNOS） were detected by immunohistochemistry staining in cerebral cortex in 4 groups of Sprague - Dawley （SD） rats （ n = 12. 3 in each group） which were grouped as that of the rabbits. RESULTS： LPS administration resulted in lower MAP than that in control group （ P 〈 0.01 ）. Hydropic degeneration of neurons and severe injuries to capillaries were observed in cerebral cortex of ES rabbits. LPS administration induced the expression of iNOS protein in the cytoplasm of neurocytes, and lead to stronger positive signals of nNOS than that in control group. NOS activity, NO2^-/NO3^- level and MDA content were higher （ P 〈 0.05, P 〈 0.01 and P 〈 0.01 ）, while SOD activity was lower in cerebral cortex of ES rabbits than those in control group （ P 〈 0.01 ）. CCK - 8 pre - administration alleviated the changes indueed by LPS, while Pro pre - administration aggravated those alterations. CONCLUSION： CCK- 8 protects brain tissues against the injury induced by LPS, which may be associated with its effects of suppressing the overproduction of NO and free radicals.