短管兔耳草总黄酮降低阿尔茨海默病模型小鼠大脑皮层及海马组织炎性细胞因子的水平

Total flavones derived from Lagotis brevituba maxim reduce the levels of inflammatory cytokines in cerebral cortex and hippocampus of Alzheimer's disease mice

目的探讨短管兔耳草总黄酮(TF-LBM)治疗阿尔茨海默病(AD)的作用机制。方法 8月龄SAMP8小鼠50只,随机分为模型组,阳性药物组,低、中、高剂量TF-LBM组5组,每组10只;8月龄SAMR1小鼠10只为正常老化组。低、中、高剂量TF-LBM组以(150、300、600)mg/kg TF-LBM灌胃,阳性药物组以0.65 g/kg盐酸多奈哌齐灌胃,模型组和正常老化组用溶解TF-LBM等量蒸馏水灌胃。8周后,进行Morris水迷宫实验,计算各组小鼠定位航行潜伏期。行为学实验后进行取材,分别取各组小鼠大脑皮层组织及海马CA1区组织进行检测,应用放射免疫法检测药物对小鼠大脑皮层及海马白细胞介素1β(IL-1β)、白细胞介素6(IL-6)、肿瘤坏死因子α(TNF-α)含量的影响。结果短管兔耳草总黄酮对小鼠行为学干预结果观察:与模型组相比,正常老化组、阳性药物组、高剂量组小鼠逃逸潜伏期明显缩短;与正常老化组相比,模型组小鼠皮层组织中IL-1β、IL-6、TNF-α显著增高;与模型组相比,低剂量TF-LBM组IL-1β含量无明显差异,而中剂量TF-LBM组、高剂量TF-LBM组及阳性对照组IL-1β含量降低。低剂量TF-LBM组、中剂量TF-LBM组、高剂量TF-LBM组及阳性对照组IL-6含量均降低。低剂量TF-LBM组及中剂量TF-LBM组TNF-α含量无明显差异,而高剂量TF-LBM组及阳性对照组TNF-α含量降低。与正常老化组相比,模型组小鼠海马组织中IL-1β、IL-6、TNF-α显著增高;与模型组相比,低、中、高剂量TF-LBM组及阳性对照组IL-1β、IL-6、TNF-α含量均降低。结论短管兔耳草总黄酮可以使SAMP8小鼠行为学得到改善,TF-LBM能够降低脑皮层及海马CA1区组织IL-1β、IL-6、TNF-α含量。

Objective To investigate the mechanism behind the treatment of Alzheimer＇s disease （AD） with total flavones derived from Lagotis brevituba maxim （TF-LBM）. Methods Fifty SAMP8 mice （aged 8 months） were randomly divided into 5 groups, （150, 300, 600） mg/kg TF-LBM groups, 0.65 g/kg donepezil HCI group and AD model group; 10 SAMR1 mice （aged 8 months） were used as a control group of normal aging. The AD model group and the normal aging control group were given the same volume of distilled water as TF-LBM groups. Eight weeks after intragastric administration, Morris water maze experiment was conducted to calculate the latency of place navigation. After the behavioral experiment, the brain cortical tissue and hippocampus （CA1 region） of the mice from various groups were taken to observe the morphological changes of the cortical tissue and hippocampus and test IL-1β, IL-6, TNF-α content. Results Compared with the model group, the escape latency of the normal aging group, the high-dose TF-LBM group and the donepezil HCI group were evidently shortened; compared with the normal aging group, IL-1β, IL-6, TNF-α of the model group increased significantly; compared with the model group, IL-1β content of the low-dose TF-LBM group had no obvious difference, while IL-1β content of the median-dose and high-dose TF-LBM groups and the donepezU HCI group decreased significantly; IL-6 content decreased in all TF-LBM groups and the donepezil HCI group; TNF-α level in the low-dose and median-dose TF-LBM groups had no evident difference, while it was reduced significantly in the high-dose TF-LBM group and the donepezil HCI group. Compared with the normal aging group, IL-1β, IL-6 and TNF-α content of the model group increased significantly; compared with the model group, IL-1β, IL-6 and TNF-α content of all TF-LBM groups and the donepezil HCI group decreased. Conclusion TF-LBM can improve the behavior change of SAMP8 mice with AD. TF-LBM can reduce the content of IL-6, IL-1β and TNF-α in cerebral cortex and hippocampus CA1.