摘要
目的探讨外源性胰岛素样生长因子-1(IGF-1)对全脑缺血大鼠学习记忆能力的影响及其可能的作用机制。方法采用简单随机分组,将110只Wistar雄性大鼠分为正常组、假手术组、全脑缺血模型组、模型给药组1及模型给药组2,正常组和假手术组各10只,全脑缺血模型组、模型给药组1及模型给药组2各30只。各手术组大鼠置管于侧脑室,置管后第6天采用改良Pulsinelli四血管阻断法建立全脑缺血模型。全脑缺血模型组、模型给药组1、模型给药组2大鼠分别侧脑室注射生理盐水10μL、IGF-1(0.2μg/μL)10μL、IGF-1+PPP[腹腔注射阻断剂PPP (20 mg/kg)30 min后,侧脑室注射IGF-1(0.2μg/μL)10μL],1次/d,共7 d。假手术组大鼠侧脑室注射生理盐水10μL。造模前后分别以Morris水迷宫实验测试各组大鼠学习记忆能力;HE染色观察海马CA1区神经细胞凋亡情况;免疫组化法检测海马组织p-Akt和p-mTOR蛋白的表达。结果与全脑缺血模型组比较,模型给药组1平均逃避潜伏期显著缩短(P <0.05),跨跃平台次数和原平台象限游泳时间显著增加(P <0.05);海马CA1区细胞数增加,排列整齐均匀,结构较清晰;p-Akt、p-mTOR蛋白的表达更高(P <0.05)。结论外源性IGF-1能够改善全脑缺血大鼠学习记忆能力,可能与其抑制海马CA1区细胞凋亡,并提高PI3K/Akt信号通路中p-Akt、pmTOR蛋白的表达相关。
Objective To investigate the effect of exogenous insulin-like growth factor-1 （IGF-1） on learning and memory ability in rats with global cerebral ischemia and its possible mechanism. Methods A total of 110 Wistar male rats were divided into normal group, sham operation group, global cerebral ischemia model group, model administration group 1 and model administration group 2; there were 10 rats in each of the normal group and sham operation group. There were 30 rats in each of the whole cerebral ischemia model group, the model drug administration group 1 and the model drug administration group 2. All operated groups were embedded micro-injection catheter into the lateral ventricle, and the whole cerebral ischemia model was established on the 6th day after catheterization with modified Pusinelli four-vessel blockade. Rats in the global cerebral ischemia model group, model drug administration group 1, and model drug administration group 2 were injected with 10 μL of normal saline, IGF-1 （0.2 μg/μL） 10 μL, and IGF-1＋PPP （after intraperitoneal injection of blocker PPP 20 mg/kg for 30 min, IGF-1 （0.2 μg/μL） 10 μL was injected into the lateral ventricle）, once a day for 7 d. In the sham operation group, NS 10 μL was injected into the lateral ventricle of rats. Morris water maze test was used to test the learning and memory ability of rats in each group before and after administration. HE staining was used to observe the apoptosis of hippocampal CA1 neurons. Immunohistochemistry was used to detect the expression of p-Akt and p-mTOR proteins in hippocampus. Results Compared with the global cerebral ischemia model group, the average escape latency of the model administration group 1 was significantly shortened （P 〈 0.05）, the number of straddle platform and the original platform quadrant swimming time increased significantly （P 〈 0.05）; the number of cells in the hippocampal CA1 area increased. The arrangement was uniform and the structure was clear; the expression of p-Akt and p-mTOR protein were higher （P 〈 0.05）. Conclusion The learning and memory ability in rats with global cerebral ischemia was improved by exogenous IGF-1. This may be related to the inhibition of apoptosis in the hippocampal CA1 region and the enhancement of the expression of p-Akt and p-mTOR proteins in the PI3K/Akt signaling pathway.
作者
李永莉
赵婧
刘黎明
张全波
刘利
吴碧华
LI Yongli;ZHAO Jing;LIU Liming;ZHANG Quanbo;LIU Li;WU Bihua(Department of Geriatric,the Affiliated Hospital of North Sichuan Medical College,Sichuan Province,Nanchong,637000,China;Department of Pediatrics,the Affiliated Hospital of North Sichuan Medical College,Sichuan Province,Nanchong,637000,China)
出处
《中国医药导报》
CAS
2018年第31期8-11,共4页
China Medical Herald
基金
四川省卫生厅科研课题(130339)
