摘要
目的:观察小檗碱对糖尿病认知功能障碍模型小鼠AGEs/RAGE/NF-κB信号通路的作用,并探讨小檗碱缓解糖尿病认知功能障碍的相关机制。方法:将实验小鼠随机分为空白组,模型组,小檗碱低、中、高剂量组,除空白组外,其他各组制备糖尿病认知功能障碍模型。造模成功后小檗碱低、中、高剂量组分别给予不同剂量的小檗碱,空白组和模型组给予等体积的生理盐水。Morris水迷宫检测小鼠的学习记忆能力,尼氏染色观察小鼠海马病理形态变化,ELISA检测小鼠血清中肿瘤坏死因子α(tumor necrosis factor-α,TNF-α)和白细胞介素1β(interleukin-1β,IL-1β)的表达,Real time-PCR和Western bolt检测海马中晚期糖基化终末产物(advanced glycation end products,AGEs)、晚期糖蛋白终末产物受体(receptor for advanced glycation end products,RAGE)、核因子κB(nuclear factor-κB,NF-κB)的基因和蛋白表达水平。结果:与空白组比较,模型组小鼠上平台潜伏期、游泳总路程和第1次抵原平台时间明显增加(P<0.01),穿越平台次数、目标象限时间则明显减少(P<0.01)。与模型组相比,小檗碱高剂量组小鼠上平台潜伏期、游泳总路程和第1次抵原平台时间均有不同程度减少(P<0.05),穿越平台次数、目标象限时间则有不同程度增加(P<0.05)。空白组小鼠海马CA3区神经元排列均匀整齐,细胞核饱满,尼氏体染色均匀,大小均一。模型组小鼠海马CA3区神经元减少,尼氏体固缩、深染。小檗碱高剂量组神经元恢复较好,排列较整齐,尼氏体固缩、深染明显好转。与空白组相比,模型组小鼠血清中TNF-α、IL-1β表达水平及海马中AGEs、RAGE、NF-κB的mRNA和蛋白表达水平均升高(P<0.05),与模型组相比,小檗碱高剂量组小鼠血清中TNF-α、IL-1β水平及海马中AGEs、RAGE、NF-κB的mRNA和蛋白表达均下降(P<0.05)。结论:小檗碱能缓解糖尿病认知功能障碍模型小鼠的记忆缺陷,其机制可能�
Objective:To observe the effect of berberine on AGEs/RAGE/NF-κB signaling pathway in diabetic cognitive impairment(DCI)mice model,and to explore the possible mechanism of berberine in alleviating diabetic cognitive impairment.Methods:The experimental mice were randomly divided into the blank group,the model group,low,moderate and high doses groups of berberine,except the blank group,the mice in other groups were prepared into DCI models.After successfully establishing the models,low,moderate and high doses groups of berberine were given different doses of berberine,the blank group and the model group were given equivalent volume of physiological saline.Morris water maze was used to detect learning and memory ability in mice,Nissl staining to observe pathological changes of mice hippocampus,ELISA method to measure the expressions of TNF-αand IL-1βin the serum of mice,Real time-PCR and Western blot to deteet the expressions of AGEs,RAGE and NF-κB gene and protein in hippocampus.Results:Compared with the blank group,the incubation period of mice on platform,total swimming distance and the time of first arrival at the original platform of the mice in the model group increased notably(P<0.01),times of crossing platform and target quadrant time decreased notably(P<0.01).Compared with the model group,the incubation period of mice on platform,total swimming distance and the time of first arrival at the original platform of the mice in the high dose group of berberine reduced to different degrees(P<0.05),times of crossing platform and target quadrant time increased to different degrees(P<0.05).In the blank group,the neurons in CA3 area of hippocampus were evenly arranged,the nucleus was full,Nissl body staining was uniform,and the size was uniform.In the model group,the number of neurons in hippocampal CA3 area decreased,Nissl body pyknosis and hyperchromatism were observed.The neurons in high dose group of berberine recovered well,arranged orderly,and Nissl body pyknosis and hyperchromatism improved notably.Compared
作者
马月娥
刘春秋
MA Yuee;LIU Chunqiu(Chongqing Three Gorges Central Hospital,Wanzhou 404000,China)
出处
《西部中医药》
2021年第2期26-31,共6页
Western Journal of Traditional Chinese Medicine
基金
重庆市万州区科委项目(wzstc-2017012)。
