摘要
目的 观察黄芪-知母对糖尿病认知功能障碍(DCI)大鼠的影响,评价其神经保护作用并探讨其机制.方法 空白组大鼠采用普通饲料喂养,其余大鼠采用高脂高糖饲料联合腹腔注射链脲佐菌素(STZ)(35 mg·kg-1)建立DCI大鼠模型.造模成功后将大鼠随机分成模型组(Model)、黄芪-知母低剂量组[HQ-ZM-L,2.4 g/(kg·d)]、黄芪-知母高剂量组[HQ-ZM-H,4.8 g/(kg·d)]和二甲双胍组[Met,0.02 g/(kg·d)],每组6 只,给药 30d,给药期间每周测量大鼠体重及空腹血糖,给药结束后采用Morris水迷宫检测DCI大鼠空间记忆能力,测试结束后取大鼠全脑进行病理切片,苏木素-伊红(HE)染色观察大鼠海马组织形态变化,ELISA检测大鼠海马血清中胰岛素(INS)、白细胞介素-1β(IL-1β)、肿瘤坏死因子-α(TNF-α)和丙二醛(MDA)、超氧化物歧化酶(SOD)含量,蛋白免疫印迹法检测大鼠海马组织中JAK2、STAT3、p-JAK2、p-STAT3蛋白表达情况.结果 与空白组相比,模型组大鼠体重显著下降,空腹血糖显著上升;逃避潜伏期显著延长,穿越平台次数显著减少;海马组织神经细胞形态被破坏;IL-1β、TNF-α、MDA水平显著升高,INS水平及SOD含量显著下降;大鼠海马组织中p-JAK2、p-STAT3蛋白表达水平升高.与模型组相比,给药各组大鼠体重、空腹血糖均得到控制;逃避潜伏期均显著缩短,穿越平台次数及在目标区域活动时间和距离均增加;大鼠海马组织神经细胞形态破坏程度明显改善;IL-1β、TNF-α、MDA水平下降,INS水平及SOD含量升高;p-JAK2、p-STAT3蛋白表达水平降低.结论 黄芪-知母可以显著改善DCI大鼠的认知障碍,其机制可能与抑制JAK2/STAT3蛋白磷酸化水平,减轻炎症反应,修复大鼠海马神经损伤有关.
Abstract
Objective To determine the combined impact of Astragalus and Anemarrhenae(HQ-ZM)on diabetic cognitive impairment(DCI)rats,evaluate its neuroprotective effect,and elucidate the underlying mechanism.Methods The rats in the blank group were given a standard diet,while the remaining rats were subjected to a high-fat and high-sugar diet along with intraperitoneal injection of streptozotocin(STZ,35 mg·kg-1)to establish diabetes cognitive impairment(DCI)rat model.Once the modeling was successfully finished,the rats were randomly divided into a model group(Model),an Astragalus-Anemarrhenae low-dose group[HQ-ZM-L,2.4 g/(kg·d)],an Astragalus-Anemarrhenae high-dose group[HQ-ZM-H,4.8 g/(kg·d)],and a metformin group[Met,0.02 g/(kg·d)],with 6 rats in each group.Their respective treatments lasted 30 days.During the administration,the body weight and fasting blood glucose(FBG)levels of the rats were measured weekly.After the administration,the spatial memory of the DCI rats was tested with the Morris water maze.After the test,the whole brains of the rats were taken for pathological sections.The morphological changes in the rat hippocampus tissue were observed with hematoxylin-eosin(HE)staining.Insulin(INS)in the rat hippocampal serum was detected by ELISA.Furthermore,the levels of interleukin 1β(IL-1β),tumor necrosis factor α(TNF-α),malondialdehyde(MDA),and superoxide dismutase(SOD)were measured.The expression of JAK2,STAT3,p-JAK2,and p-STAT3 proteins in the rat hippocampus tissue was detected with Western blot.Results Compared with the blank group,the body weight of rats in the model group was greatly decreased,and the FBG was significantly increased;the escape latency was significantly prolonged,and the number of platform crossings was significantly reduced;the morphology of the hippocampal nerve cells was destroyed;the levels of IL-1β,TNF-α and MDA were significantly increased,while the content of INS and SOD was significantly decreased;the expression levels of p-JAK2 and p-STAT3 proteins in the hippocampal tissue of the rats were increased.Compared with the model group,the body weight and FBG of rats in the treatment groups were controlled;the escape latency was much shortened,and the number of platform crossings as well as the activity time and distance in the target area were increased;the morphological destruction of the hippocampal nerve cells of the rats was greatly improved;the levels of IL-1β,TNF-α,and MDA were decreased,and the content of INS and SOD was increased;and the expression levels of p-JAK2 and p-STAT3 proteins were decreased.Conclusion Combination of Astragalus and Anemarrhenae can improve the cognitive impairment in DCI rats,whose mechanism may be related to inhibiting JAK2/STAT3 protein phosphorylation levels,reducing inflammatory responses,and repairing the hippocampal nerve damage in rats.
基金项目
陕西省教育厅2022年度服务地方专项科研计划项目(22JC029)
陕西省重点研发计划项目(2021SF-072)
维普
万方数据