摘要
目的探讨四君子汤(SJZD)对糖尿病小鼠轻度认知障碍(MCI)的改善作用。方法高糖高脂饲料联合链脲佐菌素在C57小鼠中建立2型糖尿病(T2DM)模型,通过自发交替正确率筛选认知障碍小鼠。将T2DM合并MCI的小鼠随机分为空白(Control)组、T2DM组、罗格列酮(ROSI)组、多奈哌齐(DH)组、SJZD(7.5、15.0、30.0 g/kg)组,灌胃给药6 w。记录小鼠体质量和空腹血糖(FBG);自发交替实验观察对空间记忆能力影响;空腹血清胰岛素(FINS)和胰岛素抵抗指数(HOMA-IR)观察胰岛素抵抗(IR)作用;透射电镜观察血脑屏障(BBB)超微结构;免疫组化染色法观察β-淀粉样蛋白(Aβ)沉积;甘氨酸银染色法观察海马神经纤维缠结(NFTs);酶联免疫吸附试验(ELISA)检测血清FINS及海马Aβ和Tau蛋白含量。结果与Control组比较,T2DM组体质量和自发交替正确率明显降低,FBG、FINS和HOMA-IR明显增加,BBB超微结构受损,Aβ和Tau蛋白明显增加(P<0.01);与T2DM组相比,SJZD 30.0 g/kg组体质量和自发交替正确率(干预6 w)明显升高,FBG(干预6 w)、FINS和HOMA-IR均明显降低,BBB损伤情况改善,Aβ和Tau蛋白明显降低(P<0.05,P<0.01)。结论SZJD具有改善糖尿病小鼠MCI作用,其作用机制可能与调节血糖代谢、改善IR、促进BBB修复、减少脑内Aβ和Tau蛋白沉积有关。
Objective To explore the improvement effect of Sijunzi Decoction(SJZD)on mild cognitive impairment(MCI)in diabetic mice.Methods A high-sugar and high-fat diet combined with streptozotocin was used to establish a type 2 diabetes mellitus(T2DM)model in C57 mice,and cognitive impairment mice were screened by spontaneous alternating correctness.The T2DM with MCI mice were randomly divided into the blank(Control)group,T2DM group,Rosiglitazone(ROSI)group,Donepezil(DH)group and SJZD(7.5,15.0 and 30.0 g/kg)group,and administered by intragastric administration for 6 w.Mouse body mass and fasting blood glucose(FBG)were recorded;the effects on spatial memory capacity were observed in spontaneous alternation experiments;fasting serum insulin(FINS)and insulin resistance index(HOMA-IR)were used to observe the effect of insulin resistance(IR);the ultrastructure of the blood-brain barrier(BBB)was observed by transmission electron microscopy;β-amyloid(Aβ)deposition was observed by immunohistochemical staining;hippocampal neurofibrillary tangles(NFTs)were observed by glycine silver staining;the protein contents of FINS in serum,Aβand Tau protein in hippocampus were detected by enzyme-linked immunosorbent assay(ELISA).Results Compared with the Control group,body mass and spontaneous alternation correct rate were significantly lower,FBG,FINS and HOMA-IR were significantly increased,BBB ultrastructure was impaired,and Aβand Tau proteins were significantly increased in the T2DM group(P<0.01);compared with the T2DM group,body mass and spontaneous alternation correct rate(6 w of intervention)were significantly higher,FBG(6 w of intervention),FINS and HOMA-IR were significantly lower,BBB damage was improved,Aβand Tau proteins were significantly decreased in SJZD 30.0 g/kg group(P<0.05,P<0.01).Conclusions SZJD has the effect of improving MCI in T2DM mice,and its mechanism of action may be related to the regulation of glucose metabolism,improvement of IR,promotion of BBB repair,and reduction of Aβand Tau protein deposition in the brain.
作者
杨莉
孟令真
周秋玥
李辉
樊若溪
周宁娜
YANG Li;MENG Ling-Zhen;ZHOU Qiu-Yue(Yunnan University of Chinese Medicine&Yunnan Key Laboratory of Southern Medicine Utilization,Kunming 650500,Yunnan,China)
出处
《中国老年学杂志》
北大核心
2025年第4期887-893,共7页
Chinese Journal of Gerontology
基金
国家自然科学基金(82260775)
云南(昆明)杨国源专家工作站(YSZJGZZ-2020037)。
关键词
四君子汤
糖尿病
轻度认知障碍
血脑屏障
Β淀粉样蛋白
TAU蛋白
Sijunzi Decoction
Diabetes mellitus
Mild cognitive impairment
Blood-brain barrier
β-amyloid
Tau protein
