摘要
本试验利用高脂饮食联合链脲佐菌素构建Ⅱ型糖尿病(T2D)模型,旨在探究菊粉对T2D小鼠认知功能的影响。将45只小鼠随机分为3组,每组15只,单笼饲养。正常组(Con组)饲喂普通饲粮,模型组(T2D组)饲喂高脂饲粮,菊粉干预组(DI组)饲喂添加10%菊粉的高脂饲粮,适应性饲喂1周后进行8周的饲养试验。结果显示:菊粉可显著缓解T2D小鼠体重损失(从第4周开始)(P<0.05),显著或极显著降低空腹血糖(从第4周开始)(P<0.05或P<0.01);显著降低血清低密度脂蛋白胆固醇(LDL-C)和总胆固醇(TC)水平(P<0.05),并显著升高血清高密度脂蛋白胆固醇(HDL-C)水平(P<0.05)。此外,菊粉可改善T2D小鼠认知行为和海马神经元损伤;显著或极显著上调海马中核因子E2相关因子2(Nrf2)和血红素氧合酶-1(HO-1)的mRNA和蛋白相对表达量(P<0.05或P<0.01),极显著下调高迁移率族蛋白B1(HMGB1)的蛋白相对表达量(P<0.01);显著降低血清与海马中白细胞介素-1β(IL-1β)和肿瘤坏死因子-α(TNF-α)以及海马中白细胞介素-6(IL-6)含量(P<0.05);显著降低海马中丙二醛(MDA)含量(P<0.05),极显著升高超氧化物歧化酶(SOD)和谷胱甘肽过氧化物酶(GSH-Px)活性(P<0.01)。T2D小鼠结肠中乳球菌属(Lactococcus)、魏斯氏菌属(Weissella)、杜氏杆菌属(Dubosiella)、库特氏菌属(Kurthia)和丹毒丝菌科未分类属(unclassified_f_Erysipelotrichaceae)等富集,结肠内容物中乙酸、丁酸、异戊酸、戊酸、己酸和总短链脂肪酸(SCFAs)含量均极显著降低(P<0.01);菊粉的添加使T2D小鼠结肠中双歧杆菌属(Bifidobacterium)、粪杆菌属(Faecalibaculum)和回肠杆菌属(Ileobacterium)等富集,结肠内容物中乙酸、丁酸、异戊酸、戊酸和己酸含量显著或极显著增加(P<0.05或P<0.01)。综上可知,菊粉可调节结肠菌群结构及其代谢产物SCFAs的产生,改善T2D小鼠的体重和空腹血糖,调节血脂水平、血清与海马中炎症因子含量,调控海马中Nrf2、HO-1和HMGB1表达,同时改善海马中氧化应激指标,对T2D小鼠海马神经元损伤和认知行为起到改善作用。
This study aimed to explore the effects of inulin on cognitive function of type 2 diabetes(T2D)mice.The T2D model was constructed by high-fat diet combined with streptozotocin.Forty-five mice were randomly divided into 3 groups with 15 mice in each group,and each mouse was kept in a single cage.Mice in normal group(Con group)were fed with a normal diet,those in model group(T2D group)were fed a high-fat diet,and those in inulin intervention group(DI group)were fed the high-fat diet supplemented with 10%inulin.The feeding experiment was carried out for 8 weeks after adaptive feeding for 1 week.The results showed that inulin significantly alleviated the weight loss in T2D mice(starting from week 4,P<0.05),significantly reduced the fasting blood glucose(starting from week 4,P<0.05),significantly decreased serum low-density lipoprotein-cholesterol(LDL-C)and total cholesterol(TC)levels(P<0.05),and significantly increased serum high-density lipoprotein-cholesterol(HDL-C)level(P<0.05).In addition,inulin improved the cognitive behavioral and hippocampal neuronal damage in T2D mice,significantly or extremely significantly un-regulated the mRNA and protein relative expression levels of nuclear factor E2 related factor 2(Nrf2)and heme oxygenase-1(HO-1)(P<0.05 or P<0.01),and extremely significantly down-regulated the protein relative expression level of high mobility group box protein 1(HMGB1)(P<0.01).Inulin significantly decreased the contents of interleukin-1β(IL-1β)and tumor necrosis factor-α(TNF-α)in serum and hippocampus,and interleukin-6(IL-6)in hippocampus(P<0.05).Inulin significantly decreased the content of malondialdehyde(MDA)in hippocampus(P<0.05),and extremely significantly increased the activities of superoxide dismutase(SOD)and glutathione peroxidase(GSH-Px)in hippocampus(P<0.01).The enrichment of Lactobacillus,Weissella,Dubosiella,Kurthia and unclassified_f_erysipelotrichaceae in T2D mice,and resulted in an extremely significantly decrease in the contents of acetic acid,butyric acid,isovaleric acid,valeric acid,hexanoic acid and total short-chain fatty acids(SCFAs)in the colon contents(P<0.01);the addition of inulin enriched Bifidobacterium,Faecalibacterium and Ileobacterium in T2D mice,and significantly or extremely significantly increased the contents of acetic acid,butyric acid,isovaleric acid,valeric acid andhexanoic acid in the colon contents(P<0.05 or P<0.01).In conclusion,inulin can affect the structure of the colon microbiota and the production of its metabolites SCFAs,improve T2D mice’weight and FBG,regulate blood lipid level,serum and hippocampal inflammatory factor contents,regulate Nrf2,HO-1 and HMGB1 expression and improve oxidative stress-related indicators in the hippocampus,and it play an important role in reducing hippocampal neuronal damage and cognitive behaviors.
作者
冯焱
蒙爱
魏思昂
李旭旭
王磊
赵燕
薛智权
丁志文
FENG Yan;MENG Ai;WEI Siang;LI Xuxu;WANG Lei;ZHAO Yan;XUE Zhiquan;DING Zhiwen(College of Life Science,Shanxi Agricultural University,Taigu 030800,China;Zhongshan Hospital Affiliated to Fudan University,Shanghai 200030,China;College of Basic Medicine,Shanxi Medical University,Taiyuan 030001,China;College of Animal Science,Shanxi Agricultural University,Taigu 030800,China)
出处
《动物营养学报》
CAS
CSCD
北大核心
2024年第11期7305-7319,共15页
CHINESE JOURNAL OF ANIMAL NUTRITION
基金
山西省自然科学基金资助项目(20210302124081)
山西省科研基金项目(2022HX159)。
