Wei Peng, Ling Yi-Ling, Niu Zhi-Yun, Duan Guo-Chen, Yang Shi-Fang
Department of Pathophysiology, Hebei Medical University, Shijiazhuang 050017, China.
Zhongguo Ying Yong Sheng Li Xue Za Zhi. 2006 May;22(2):186-9.
To study the effects and the mechanisms of cholecystokinin octapeptide(CCK-8) on hippocampal injury during endotoxic shock (ES).
Rabbits were injected intravenously with lipopolysaccharide (LPS, 8 mg/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.
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.
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.
研究八肽胆囊收缩素（CCK - 8）对内毒素休克（ES）时海马损伤的影响及其机制。
静脉注射脂多糖（LPS，8 mg/kg）制备家兔ES模型。32只家兔随机分为4组（n = 8）：对照组（静脉注射生理盐水）、LPS组、CCK - 8 + LPS组（LPS注射前30 min静脉注射CCK - 8）、丙谷胺（Pro，CCK受体非特异性拮抗剂）+ LPS组（LPS注射前30 min静脉注射Pro）。测量平均动脉压（MAP）变化。通过光镜（LM）和透射电镜（TEM）观察海马形态学变化。检测海马中一氧化氮合酶（NOS）、超氧化物歧化酶（SOD）活性，一氧化氮（NO）、丙二醛（MDA）含量变化。选取12只Sprague - Dawley大鼠，分组同家兔，采用免疫组织化学染色法检测诱导型NOS（iNOS）和神经元型NOS（nNOS）蛋白表达。
LPS注射后MAP显著降低（与对照组相比，P < 0.01），海马神经元出现水样变性。与对照组相比，ES家兔海马中NOS活性、NO水平和MDA含量显著升高（P < 0.05、P < 0.01和P < 0.05），而SOD活性降低（P < 0.01）。LPS注射诱导海马神经元胞质中iNOS蛋白表达，nNOS阳性信号较对照组增强。预先注射CCK - 8可减轻LPS诱导的变化，而预先注射Pro则加重这些改变。
CCK - 8可保护ES时海马神经元免受LPS诱导的损伤，这可能与其抑制NO和自由基过度产生的作用有关。
