【摘要】 目的 探究有氧运动是否通过影响核因子-κB(NF-κB)/Nod样受体蛋白3(NLRP3)信号通路缓解睡眠剥夺诱导的老年大鼠焦虑和认知功能障碍。方法 随机数字表法将大鼠分为空白对照组、模型组、有氧运动组,每组12只。大鼠通过改良多平台水环境法复制慢性睡眠剥夺大鼠模型。有氧运动组进行12周的有氧运动,空白对照组及模型组安静饲养。通过高架十字迷宫实验评估大鼠焦虑样行为,通过新物体识别实验评估大鼠短期识别记忆能力,ELISA实验检测大鼠海马组织中促炎和免疫激活因子白细胞介素-1β(IL-1β)、白细胞介素-18(IL-18)、巨噬细胞炎症蛋白-2(MIP-2)蛋白表达水平,采用免疫荧光标记海马中星形胶质细胞标记物胶质纤维酸性蛋白(GFAP),并检测分别与补体C3~+、S100A~+的共标情况,以了解海马中星形胶质细胞A1、A2分型情况,Western blot检测大鼠海马组织中p-NF-κB/NF-κB、NLRP3、半胱氨酸天冬氨酸蛋白酶1(Caspase-1)、脑源性神经营养因子(BDNF)蛋白的表达。结果 相对于空白对照组,模型组在封闭臂上的停留时间、进入封闭臂的次数、后肢直立次数显著增加(均P<0.01),在开放臂上的停留时间、进入开放臂的次数、平均梳理时间显著减少(均P<0.01),大鼠探索新物体的时间、对新物体的分辨比显著降低(均P<0.01),大鼠海马组织中促炎和免疫激活因子IL-1β、IL-18、MIP-2蛋白表达显著增加(均P<0.01),大鼠海马区域A1型星形胶质细胞数量显著增加(均P<0.01),A2型星形胶质细胞数量显著减少(均P<0.01),大鼠海马组织中p-NF-κB/NF-κB、NLRP3、Caspase-1蛋白表达显著增加(均P<0.01)、BDNF表达显著降低(均P<0.01);相对于模型组,有氧运动组在封闭臂上的停留时间、进入封闭臂的次数、后肢直立次数显著减少(均P<0.01),在开放臂上的停留时间、进入开放臂的次数、平均梳理时间显著增加(均P<0.01),大鼠探索新物体的时间、对新物体的分辨比显著升高(均P<0.01),大鼠海马组织中促炎和免疫激活因子IL-1β、IL-18、MIP-2蛋白表达显著降低(均P<0.01),大鼠海马区域A1型星形胶质细胞数量显著减少(均P<0.01),A2型星形胶质细胞数量显著增加(均P<0.01),大鼠海马组织中p-NF-κB/NF-κB、NLRP3、Caspase-1蛋白表达显著降低(均P<0.01)、BDNF表达显著增加(均P<0.01)。结论 有氧运动抑制NF-κB/NLRP3信号通路缓解睡眠剥夺诱导的老年大鼠焦虑和认知功能障碍。更多还原

【Abstract】 Objective To explore whether aerobic exercise alleviates anxiety and cognitive dysfunction induced by sleep deprivation in elderly rats by affecting the nuclear factor-κB(NF-κB) /NODlike receptor protein3( NLRP3) signaling pathway. Methods Rats were randomly divided into the blank control group,the model group and the aerobic exercise group by random number table method,with12rats in each group.Rats replicated the rat model of chronic sleep deprivation by the modified multi-platform water environment method.The aerobic exercise group underwent12weeks of aerobic exercise,while the blank control group and the model group were raised quietly.The anxiety-like behaviors of rats were evaluated by the elevated cross maze experiment,and the short-term recognition and memory abilities of rats were evaluated by the new object recognition experiment.ELISA experiment was used to detect the expression levels of pro-inflammatory and immune activator factors interleukin-1β(IL-1β),interleukin-18(IL-18),and macrophage inflammatory protein-2(MIP-2) proteins in the hippocampal tissue of rats.The astrocyte marker glial fibrillary acidic protein(GFAP)in the hippocampal tissue was labeled by immunofluorescence.And the co-labeling conditions with complement C3~+ and S100A~+ respectively were detected to understand the typing of astrocytes A1and A2in the hippocampus.Western blot was applied to detect the expressions of p-NF-κB/NF-κB, NLRP3, caspase-1 and brain-derived neurotrophic factor(BDNF) proteins in the hippocampal tissue of rats. Results Compared with the blank control group, the residence time on the closed arm, the number of times entering the closed arm, and the number of times the hind limb stood upright in the model group significantly increased (all P<0. 01), while the residence time on the open arm,the number of times entering the open arm,and the average grooming time significantly decreased(all P<0.01). The time for rats to explore new objects and the resolution ratio of new objects were significantly decreased(all P<0.01), the protein expressions of pro-inflammatory and immune activating factors IL-1β,IL-18,and MIP-2in the hippocampal tissue of rats were significantly increased(all P<0.01), and the number of type A1 astrocytes in the hippocampal region of rats was significantly increased(all P<0.01). The number of type A2 astrocytes decreased significantly(all P<0.01), and the protein expressions of p-NF-κB/NF-κB, NLRP3,and Caspase-1in the hippocampal tissue of rats increased significantly(all P<0.01), while the expression of BDNF decreased significantly(all P<0.01). Compared with the model group, the stay time on the closed arm, the number of times entering the closed arm,and the number of times the hind limb stood upright in the aerobic exercise group were significantly reduced(all P<0.01), while the stay time on the open arm, the number of times entering the open arm, and the average grooming time were significantly increased(all P<0.01). The time for rats to explore new objects and the resolution ratio of new objects were significantly increased(all P<0.01), the protein expressions of pro-inflammatory and immune activator factors IL-1 β, IL-18, and MIP-2 in the hippocampal tissue of rats were significantly decreased(all P<0.01), and the number of type A1 astrocytes in the hippocampal region of rats was significantly reduced(all P<0.01). The number of type A2 astrocytes increased significantly(all P<0.01), while the protein expressions of p-NF-κB/NF-κB, NLRP3 and Caspase-1 in the hippocampal tissue of rats decreased significantly(all P<0.01), and the expression of BDNF increased significantly(all P<0.01). Conclusion Aerobic exercise inhibits the NF-κB/NLRP3 signaling pathway to alleviate anxiety and cognitive dysfunction induced by sleep deprivation in elderly rats.更多还原