Department of Neurosurgery, Peking Union Medical College Hospital, Chinese Academy of Medical Science, Beijing 100730, China.
Chin Med J (Engl). 2009 Sep 5;122(17):2022-6.
Cholecystokinin (CCK) is one of the richest neuropeptides in the mammalian brain, which is mainly distributed in the cerebral cortex, hippocampus, thalamus and caudate-putamen. CCK is implicated in a variety of behavioral functions such as food intake, learning, memory, anxiety, pain and neuroprotection. The current research results for CCK are obtained mainly through injection of CCK peptide into the body. The key issues of whether CCK can regulate diet by a central pathway and whether there are long-term regulation effects on diet are still unresolved. In this study, the effects of CCK on food intake in transgenic mice were investigated.
Transgenic mice were created by microinjection of the PDGF-CCK construct into male pronucleus of the zygotes. The genomic phonetype of transgenic mice were identified by PCR. The expression of PDGF-CCK was analyzed by Western blotting. Body weight, plasma glucose, cholesterol and triglycerides were assayed and analyzed.
Two PDGF-CCK transgenic independent lines were established and exhibited a high-levels brain-specific transgene expression compared with that of nontransgenic littermate controls. The food intake of male CCK transgenic mice was decreased by 5% - 10% with the same levels of water consumed compared with wild type mice. The food intake in female mice was not obviously changed. In the transgenic mice the bodyweight was lower and plasma glucose was higher compared with the nontransgenic littermate controls.
The high expression of the CCK gene in the brain can decrease body weight and increase plasma glucose. The differences in food intake between the males and females require further study.
胆囊收缩素（CCK）是哺乳动物脑中最丰富的神经肽之一，主要分布于大脑皮层、海马体、丘脑和尾壳核。CCK 参与多种行为功能，如摄食、学习、记忆、焦虑、疼痛和神经保护。目前对 CCK 的研究结果主要通过向体内注射 CCK 肽获得。CCK 是否能通过中枢途径调节饮食以及对饮食是否有长期调节作用等关键问题仍未解决。本研究旨在探讨 CCK 对转基因小鼠摄食的影响。
通过将 PDGF-CCK 构建体微注射到受精卵的雄性原核中，创建转基因小鼠。通过 PCR 鉴定转基因小鼠的基因组音型。通过 Western blot 分析 PDGF-CCK 的表达。检测和分析体重、血浆葡萄糖、胆固醇和甘油三酯。
成功建立了两条 PDGF-CCK 转基因独立品系，与非转基因同窝仔鼠相比，其脑内的转基因表达水平显著升高。雄性 CCK 转基因小鼠的食物摄入量比野生型小鼠减少了 5%-10%，但饮水量相同。雌性小鼠的食物摄入量没有明显变化。与非转基因同窝仔鼠相比，转基因小鼠的体重较低，血浆葡萄糖水平较高。
脑内 CCK 基因的高表达可降低体重并增加血浆葡萄糖。雌雄小鼠摄食的差异需要进一步研究。
