MCP-1诱导认知功能障碍大鼠模型制作方法的建立

Establishment of a method for making a rat model of cognitive impairment induced by MCP-1

目的:通过双侧海马内注射单核细胞趋化蛋白-1(MCP-1)建立认知功能障碍大鼠模型,探索MCP-1对大鼠学习记忆及认知功能的影响。方法:将实验大鼠随机分为空白对照组、假手术组、模型组。模型组根据MCP-1的剂量分为5 ng、50 ng、150 ng和300 ng MCP-1组4个亚组。双侧海马内注射MCP-1制作认知功能障碍大鼠模型,通过HE染色观察大鼠海马组织神经元的形态结构并筛选MCP-1的适宜剂量,采用Morris水迷宫实验和新物体识别实验检测大鼠的学习记忆能力及认知功能。结果:HE染色结果显示,4个不同剂量的MCP-1对大鼠海马神经元均有形态学上的损伤;与假手术组相比,300 ng MCP-1组大鼠的逃避潜伏期及游泳距离显著延长,穿越次数显著减少,在平台所在象限的路程和时间百分比显著降低(均P<0.01);300 ng MCP-1组与假手术组的辨别指数相比,差异无统计学意义(P>0.05)。结论:在大鼠双侧海马内注射MCP-1能成功建立认知功能障碍大鼠模型,其中,对海马神经组织造成最显著损伤的300 ng MCP-1,能显著降低大鼠学习记忆能力,并损伤模型大鼠的认知功能。

Objective: To established a rat model of cognitive impairment by injecting monocyte chemoattractant protein-1 (MCP-1) into the bilateral hippocampus of rats to study the effects of MCP-1 on learning,memory and cognitive function in rats. Methods: Rats were randomly divided into control group,sham group,model group (5 ng,50 ng,150 ng and 300 ng MCP-1).A rat model of cognitive dysfunction was induced by injection of MCP-1 in bilateral hippocampus.The morphology of hippocampal neurons was observed by HE staining.Morris water maze test and new object recognition test were used to test the learning and memory ability and cognitive function of rats. Results: HE staining showed that four different doses of MCP-1 had a morphological effect on rat hippocampal neurons.Compared with the sham group,the escape latency and the swimming distance were significantly increased in 300 ng MCP-1 group,and the number of crossings,the percentage of distance and time in the quadrant of the platform were significantly reduced ( P <0.01).There was no significant difference in discrimination index between 300 ng MCP-1 group and sham group ( P >0.05). Conclusion: Different concentrations of MCP-1 injected in bilateral hippocampus could damage the hippocampal nerve tissue structure in varying degrees,and 300 ng MCP-1 caused the most significant damage to the hippocampal nerve tissue,reduced the learning and memory ability and impaired the cognitive function of model rats.