腹腔注射LPS建立认知功能障碍相关的中枢神经系统免疫炎症小鼠模型

Model of neuroinflammation associated with cognitive dysfunction established by intraperitoneal injection of LPS

目的:建立认知功能障碍相关的中枢神经系统免疫炎症小鼠模型。方法:实验采用9~11周的C57/6J雄性小鼠,腹腔注射脂多糖(lipopolysaccharide,LPS)500μg/kg或750μg/kg。采用Morris水迷宫和避暗实验评价小鼠的认知功能,爬杆试验检测小鼠的运动协调性。免疫荧光法观察小鼠海马区神经元特异性微管相关蛋白2(microtubule-associated protein 2,MAP-2)的表达和小胶质细胞的形态和数量。Western blot实验检测小鼠脑组织匀浆液中环氧合酶2(cyclo-oxygenase-2,COX-2)和诱导型一氧化氮合酶(inducible nitric oxide synthase,iNOS)蛋白的表达。结果:Morris水迷宫结果提示,与对照组相比,LPS组小鼠逃避潜伏期延长,目标象限停留时间及穿越目标象限次数减少(P<0.05);避暗实验结果提示LPS组均能使小鼠的潜伏期缩短,错误次数增加(P<0.05);爬杆实验结果提示LPS组小鼠爬完全程时间高于正常对照组;LPS组小鼠海马区的神经元减少,小胶质细胞增加,COX-2和i NOS蛋白表达增加(P<0.01)。结论:腹腔注射LPS可引起小鼠认知功能障碍,模拟认知功能障碍相关的中枢炎症动物模型。

AIM： To establish a mouse model of immuno-inflammation in central nervous system （CNS） associated with cognitive dysfunction.METHODS： C57BL/6J male mice were divided into 3 groups.Lipopolysaccharide （LPS） was intraperitoneally injected into the mice to induce cognitive impairment. Morris water maze test, passive avoidance test and pole test were used to observe the behavioral changes of mice. The histomorphology was analyzed by the method of immunofluorescence. The detailed molecular mechanism was determined by Western blot.RESULTS： Compared with saline group, LPS induced mouse sickness behavior and memory loss. Microglia activation and neuronal loss in the hippocampus were observed. The expression of neuroinflammatory proteins COX-2 and iNOS in the brain of LPS-induced mice was increased.CONCLUSION： Intraperitoneal injection of LPS induces cognitive dysfunction in mice.