Effect of exogenous free N^(ε)-(carboxymethyl)lysine on diabetes-associated cognitive dysfunction:neuroinflammation,and metabolic disorders

Diabetes-associated cognitive dysfunction has already been attracted considerable attention.Advanced glycation end products(AGEs)from daily diets are thought to be a vital contributor to the development of this diseases.However,the effect of one of the best-characterized exogenous AGEs N^(ε)-(carboxymethyl)lysine(CML)on cognitive function is not fully reported.In the present study,diabetical Goto-Kakizaki(GK)rats were treated with free CML for 8-weeks.It was found that oral consumption of exogenous CML significantly aggravated diabetes-associated cognitive dysfunction in behavioral test.In details,exogenous CML increased levels of oxidative stress,promoted the activation of glial cells in the brain,up-regulated the release of inflammatory cytokines interleukin-6,inhibited the protein expression of the brain-derived neurotrophic factor and thus led to neuroinflammation.Furthermore,exogenous CML promoted the amyloidogenesis in the brain of GK rats,and inhibited the expression of GLUT4.Additionally,several tricarboxylic acid cycle and glutamate-glutamine/γ-aminobutyric acid cycle intermediates including pyruvate,succinic acid,glutamine,glutamate were significantly changed in brain of GK rats treated with exogenous free CML.In conclusion,exogenous free CML is a potentially noxious compounds led to aggravated diabetes-associated cognitive dysfunction which could be possibly explained by its effects on neuroinflammation,energy and neurotransmitter amino acid homeostasis.

Small extracellular vesicles secreted by induced pluripotent stem cell-derived mesenchymal stem cells improve postoperative cognitive dysfunction in mice with diabetes

Postoperative cognitive dysfunction(POCD)is a common surgical complication.Diabetes mellitus(DM)increases risk of developing POCD after surgery.DM patients with POCD seriously threaten the quality of patients’life,however,the intrinsic mechanism is unclear,and the effective treatment is deficiency.Previous studies have demonstrated neuronal loss and reduced neurogenesis in the hippocampus in mouse models of POCD.In this study,we constructed a mouse model of DM by intraperitoneal injection of streptozotocin,and then induced postoperative cognitive dysfunction by transient bilateral common carotid artery occlusion.We found that mouse models of DM-POCD exhibited the most serious cognitive impairment,as well as the most hippocampal neural stem cells(H-NSCs)loss and neurogenesis decline.Subsequently,we hypothesized that small extracellular vesicles secreted by induced pluripotent stem cell-derived mesenchymal stem cells(iMSC-sEVs)might promote neurogenesis and restore cognitive function in patients with DM-POCD.iMSC-sEVs were administered via the tail vein beginning on day 2 after surgery,and then once every 3 days for 1 month thereafter.Our results showed that iMSC-sEVs treatment significantly recovered compromised proliferation and neuronal-differentiation capacity in H-NSCs,and reversed cognitive impairment in mouse models of DM-POCD.Furthermore,miRNA sequencing and qPCR showed miR-21-5p and miR-486-5p were the highest expression in iMSC-sEVs.We found iMSC-sEVs mainly transferred miR-21-5p and miR-486-5p to promote H-NSCs proliferation and neurogenesis.As miR-21-5p was demonstrated to directly targete Epha4 and CDKN2C,while miR-486-5p can inhibit FoxO1 in NSCs.We then demonstrated iMSC-sEVs can transfer miR-21-5p and miR-486-5p to inhibit EphA4,CDKN2C,and FoxO1 expression in H-NSCs.Collectively,these results indicate significant H-NSC loss and neurogenesis reduction lead to DM-POCD,the application of iMSC-sEVs may represent a novel cell-free therapeutic tool for diabetic patients with postoperative cognitive dysfunction.

Expert Consensus on Cognitive Dysfunction in Diabetes

The incidence of diabetes is gradually increasing in China,and diabetes and associated complications,such as cognitive dysfunction have gained much attention in recent time.However,the concepts,clinical treatment,and prevention of cognitive dysfunction in patients with diabetes remain unclear.The Chinese Society of Endocrinology investigated the current national and overseas situation of cognitive dysfunction associated with diabetes.Based on research both in China and other countries worldwide,the Expert Consensus on Cognitive Dysfunction in Diabetes was established to guide physicians in the comprehensive standardized management of cognitive dysfunction in diabetes and to improve clinical outcomes in Chinese patients.This consensus presents an overview,definition and classification,epidemiology and pathogenesis,risk factors,screening,diagnosis,differential diagnosis,treatment,and prevention of cognitive dysfunction in patients with diabetes.

Three-dimensional-arterial spin labeling perfusion correlation with diabetes-associated cognitive dysfunction and vascular endothelial growth factor in type 2 diabetes mellitus rat

BACKGROUND Type 2 diabetes mellitus(T2DM) has been strongly associated with an increased risk of developing cognitive dysfunction and dementia.The mechanisms of diabetes-associated cognitive dysfunction(DACD) have not been fully elucidated to date.Some studies proved lower cerebral blood flow(CBF) in the hippocampus was associated with poor executive function and memory in T2DM.Increasing evidence showed that diabetes leads to abnormal vascular endothelial growth factor(VEGF) expression and CBF changes in humans and animal models.In this study,we hypothesized that DACD was correlated with CBF alteration as measured by three-dimensional(3D) arterial spin labeling(3D-ASL) and VEGF expression in the hippocampus.AIM To assess the correlation between CBF(measured by 3D-ASL and VEGF expression) and DACD in a rat model of T2DM.METHODS Forty Sprague-Dawley male rats were divided into control and T2DM groups.The T2DM group was established by feeding rats a high-fat diet and glucose to induce impaired glucose tolerance and then injecting them with streptozotocin to induce T2DM.Cognitive function was assessed using the Morris water maze experiment.The CBF changes were measured by 3D-ASL magnetic resonance imaging.VEGF expression was determined using immunofluorescence.RESULTS The escape latency time significantly reduced 15 wk after streptozotocin injection in the T2DM group.The total distance traveled was longer in the T2DM group;also,the platform was crossed fewer times.The percentage of distance in the target zone significantly decreased.CBF decreased in the bilateral hippocampus in the T2DM group.No difference was found between the right CBF value and the left CBF value in the T2DM group.The VEGF expression level in the hippocampus was lower in the T2DM group and correlated with the CBF value.The escape latency negatively correlated with the CBF value.The number of rats crossing the platform positively correlated with the CBF value.CONCLUSION Low CBF in the hippocampus and decreased VEGF expression might be crucial in DACD.CBF measured by 3D-ASL might serve as a noninvasive imaging biomarker for cognitive impairment associated with T2DM.

The relationship between cognitive function and having diabetes in patients treated with hemodialysis

Purpose:Patients undergoing maintenance hemodialysis(MHD)have a higher prevalence of cognitive impairment and inferior cognitive performance than the general population,and those with cognitive impairment are at higher risk of death than those without cognitive impairment.Having diabetes has been associated with an increased risk of cognitive decline in end-stage kidney disease patients treated with peritoneal dialysis or kidney transplant.However,these findings may not extend to the hemodialysis population.Thus,we aim to investigate the relationship between having diabetes and cognitive function in MHD patients.Methods:This was a cross-sectional study.A total of 203 patients treated with MHD from two blood purification centers were enrolled as subjects.The Chinese version of the Montreal Cognitive Assessment(MoCA)was utilized to assess cognitive function.Results:MHD patients with diabetes had a significantly higher prevalence of global cognitive impairment and inferior performance in global cognition,visuospatial/executive function,naming,language,abstraction and orientation tasks compared with those without diabetes.According to the multiple linear analyses,having diabetes was significantly associated with lower global cognitive function,naming,and language scores,withβcoefficients and 95%CIs of-1.30[-2.59,-0.01],-0.25[-0.47,-0.02],and-0.32[-0.58,-0.07],respectively(all P<0.05).Having diabetes could not independently predict an increased risk of global cognitive impairment.Conclusions:In MHD patients,having diabetes is significantly associated with lower cognitive function scores.Medical staff should evaluate early and focus on the decline of cognitive function in MHD patients with diabetes,in order to achieve early diagnosis and earlv intervention.

Diabetic cognitive dysfunction： a long and strenuous way from bench to clinical

Type 2 diabetes increase the risk of development of cognitive dysfunction in the elderly, in the form of short-term memory and executive function deficits. Genetic and diet-induced models of type 2 diabetes further sup- port this link displaying deficits in working memory, learning, and memory performance. The risk factors for dia- betic cognitive dysfunction include vascular disease, hypoglycemia, hyperlipidemia, adiposity, lifestyle factors, and genetic factors. Using neuronimage technologies, diabetic patients with cognitive dysfunction shows whole brain atrophy, gray matter atrophy, hippocampal atrophy, and amygdala atrophy, increased ventricular volume and white matter volume, brain infarcts, impaired network integrity, microstructural abnormality, reduced cerebral blood flow and amplitude of low-frequency fluctuations. The pathogenesis mechanisms of type 2 diabetes with cognitive dys- function involve hyperglycemia, macrovascular and microvascular diseases, insulin resistance, inflammation, apop- tosis, impaired neurogenesis, impaired blood-brain barrier, and disorder neurotransmitters. Some antidiabetic drugs and Traditional Chinese Medicine partly improve diabetic cognitive dysfunction, but more clinical investigations are demanded to verify their efficiencies and novel drugs are urgent need to develop. Large clinical studies will provide further evidences of risks factors and biomarkers for diabetic cognitive dysfunction. Both novel disease animal mod- els and advanced neuronimage technologies will help to investigate the exact pathogenesis mechanisms and to devel- op better therapeutic interventions and treatment.

Blood Pressure Variability and Its Relationship with Cognitive Function in Elderly Patients with Essential Hypertension and Type 2 Diabetes

Objective: To investigate blood pressure variability of Elder hypertensives with type 2 diabetes and its relationship with cognition. Methods: A total of 143 elderly hypertensives were enrolled and divided into diabetic group (59 cases) and non-diabetic group (84 cases). The difference of general clinical characteristics, biochemical parameters, carotid ultrasound, a neuropsychological Scales and 24-hour ambulatory blood pressure (24hABPM) parameters between the two groups of subjects were compared. Then, the two groups (diabetic group and non-diabetic group) were further divided into (Mild cognitive dysfunction) subgroup (MMSE>26) and normal cognition subgroup (MMSE≤26), respectively. On the basis of MMSE scores, the difference of the parameters of ABPM between the two subgroups was analyzed. Results: Compared with the control group, 24hSBP, 24hPP, dSBP, dPP, nSBP, nPP, 24hSSD, dSSD, nSSD, 24hSCV, dSCV and nSCV were significantly higher in the diabetic group (p<0.05). However, cognition was lower in the diabetic group. No significant difference was found in the circadian pattern of blood pressure between the two groups. 24hSSD, dSSD, nSSD, 24hSCV, dSCV, nSCV were significantly higher in the MCI subgroup than normal cognition subgroup in both diabetic and non-diabetic groups(p<0.05), and they were negatively associated with scores of MMSE, the correlation coefficient were -0.235,-0.246,-0.341,-0.158,-0.222,-0.238 (0.001≤P<0.05). Conclusion: The study showed that in the elderly with hypertension, the mean systolic blood pressure and blood pressure variability were both higher in the diabetic group, and the cognition was lower instead. Whether or not with diabetes, blood pressure variability was always higher in the MCI subgroup. Blood pressure variability increased in patients with diabetes, and was associated with cognitive decline.

2型糖尿病患者认知功能障碍风险预测模型的构建

目的探讨2型糖尿病患者认知功能障碍的影响因素并构建风险预测模型。方法采用便利抽样法选取2022年6—12月延安大学附属医院133例2型糖尿病患者为研究对象,分为非认知功能障碍组(n=63)和认知功能障碍组(n=70)。通过Logistic回归分析评估认知功能障碍的影响因素并构建风险预测模型,通过Hosmer-Lemeshow检验检测模型的拟合度,通过受试者工作特征曲线、曲线下面积等判断预测模型对认知功能障碍的诊断价值。结果2型糖尿病患者认知功能障碍患病率为52.6%。基于Logistic回归分析结果,将受教育时间(OR=0.297)、糖尿病病程(OR=3.141)、纤维蛋白原水平(OR=5.118)纳入风险预测模型。结论利用受教育时间、糖尿病病程和纤维蛋白原水平可以有效预测2型糖尿病患者发生认知功能障碍的风险。

基于“浊菀清窍”病机学说论治糖尿病认知功能障碍

随着糖尿病患病率的不断升高,糖尿病认知功能障碍已成为糖尿病常见的重要并发症之一,并严重影响患者的生活质量,给个人家庭和社会带来沉重的负担。糖尿病认知障碍的现代病理及细胞分子生物学基础是痴呆发病过程中的级联反应,包括但不限于糖脂代谢异常、β淀粉样蛋白沉积、tau蛋白过度磷酸化、胰岛素抵抗、神经炎症等导致的脑血管和血脑屏障损伤、脑神经元损伤。囿于糖尿病认知障碍目前并无明显有效的诊疗方法,蔡业峰教授基于其创新的“浊菀清窍”疾病病机假说,认为“浊菀清窍”是糖尿病认知功能障碍的病机关键,并揭示了贯穿于糖尿病认知障碍始终的病理实质“浊”和“菀”,并提出“化浊菀,开清窍”为治疗该疾病的核心治疗大法。为糖尿病认知障碍的临床诊治和学术研究提供了新的思路和方法。

允许性高碳酸血症对老年糖尿病患者术后认知功能的影响

目的探讨允许性高碳酸血症对老年糖尿病患者术后认知功能的影响。方法选择全麻下行腹腔镜上腹部手术的老年糖尿病患者60例,将患者随机分为两组:允许性高碳酸血症通气糖尿病组(DH组)和常规通气糖尿病组(DR组),每组30例。另选择全麻下行腹腔镜上腹部手术非糖尿病老年患者60例,将患者随机分为两组:允许性高碳酸血症通气非糖尿病组(NH组)和常规通气非糖尿病组(NR组),每组30例。麻醉诱导后行机械通气,调控呼吸参数使DH组和NH组维持PaCO_(2)45~65 mmHg,DR组和NR组维持PaCO_(2)35~45 mmHg。记录气腹前5 min及气腹后5、15、30 min的PETCO_(2),并采集以上时点桡动脉、颈内静脉血样行血气分析,记录pH值、PaCO_(2),计算动脉-颈内静脉血氧含量差(Da-jvO_(2))和脑氧摄取率(CERO_(2))。检测麻醉诱导前及术后3 d的血清S100β蛋白浓度。记录术前1 d和术后1、3、7 d的蒙特利尔认知评估量表(MoCA)评分和术后认知功能障碍(POCD)的发生情况。结果与气腹前5 min比较,四组气腹后5、15、30 min时PETCO_(2)和PaCO_(2)明显升高,pH值、Da-jvO_(2)和CERO_(2)明显降低(P<0.05)。与麻醉诱导前比较,四组术后3 d血清S100β蛋白浓度均明显升高(P<0.05)。与术前1 d比较,四组术后1、3 d MoCA评分均明显降低(P<0.05)。与DR组比较,DH组气腹前5 min及气腹后5、15、30 min时PETCO_(2)明显升高,pH值、Da-jvO_(2)和CERO_(2)明显降低,术后3 d血清S100β蛋白浓度明显降低,术后1、3 d MoCA评分明显升高,POCD发生率明显降低(P<0.05)。与NR组比较,NH组气腹前5 min及气腹后5、15、30 min时PETCO_(2)明显升高,pH值、Da-jvO_(2)和CERO_(2)明显降低,术后3 d血清S100β蛋白浓度明显降低,术后1、3 d MoCA评分明显升高,POCD发生率明显降低(P<0.05)。与NH组比较,DH组气腹前5 min及气腹后5、15、30 min时Da-jvO_(2)和CERO_(2)明显升高,术后3 d血清S100β蛋白浓度明显升高,术后1、3 d MoCA评分明显降低(P<0.05)。结论允许性高碳酸血症可改善老年糖尿病患者术中脑氧代谢,降低术后血清S100β蛋白浓度,降低术后认知功能障碍的发生率。

糖尿病合并TREM2突变相关认知功能障碍的生物信息学分析

目的通过生物信息学分析探寻糖尿病(DM)合并髓系细胞触发受体-2(TREM2)突变相关认知功能障碍的核心基因及可能的治疗靶点。方法利用微阵列数据分析,分别得到糖尿病合并TREM2突变相关认知功能障碍2个疾病的差异基因并交集得到共同的差异基因。对其进行GO分析、KEGG和Reactome通路分析,利用在线数据库构建蛋白质-蛋白质相互作用网络(PPI);最后利用水迷宫检测糖尿病和TREM2对小鼠空间学习记忆能力的影响;利用蛋白质免疫印迹检测SNAP25表达的变化。结果在这2个数据集中,有19个基因变化相同,这些基因主要在与神经元和代谢相关的生物过程和通路富集。根据PPI分析结果,确定DNER、GFAP、GRM5、SNAP25为核心基因。Trem2敲除加重糖尿病模型小鼠空间学习记忆障碍,糖尿病小鼠海马SNAP25表达明显增加,Trem2敲除后SNAP25表达显著降低。结论本研究发现19个糖尿病合并认知功能障碍中TREM2相关基因,得到4个核心基因。这些结果为治疗糖尿病合并认知功能障碍患者提供新的实验依据。

T2DM患者丘脑微观结构改变与轻度认知功能障碍及肠道短链脂肪酸的相关性

目的 利用扩散峰度成像(diffusion kurtosis imaging, DKI)评估2型糖尿病(type 2 diabetes mellitus, T2DM)患者背侧丘脑的微观结构改变,探讨DKI的参数变化与认知功能评分及肠道短链脂肪酸改变的相关性。材料与方法 对57例T2DM患者[其中T2DM伴轻度认知障碍(mild cognitive impairment,MCI)患者(T2DM-MCI组) 29例、 T2DM不伴MCI患者(T2DM-nonMCI组)28例]和30例健康对照(healthy control, HC)(HC组)双侧丘脑进行DKI数据采集,测量其各向异性分数(fractional anisotropy, FA)值、平均峰度(mean kurtosis, MK)值、径向峰度(radial kurtosis, RK)值及峰度分数各向异性(fractional anisotropy of kurtosis, FAK)值;同时行肠道代谢物短链脂肪酸检测;将3组间差异脑区的平均DKI参数值与认知功能评分及短链脂肪酸行相关性分析。结果 T2DM-MCI组左侧丘脑MK值均低于T2DM-nonMCI及HC组,且T2DM-MCI与T2DM-nonMCI组间差异具有统计学意义(P<0.05);与HC组比较,T2DM-MCI组左侧丘脑RK、右侧丘脑FA、KFA值均减低(P<0.05),两两比较显示左侧丘脑RK值在HC与T2DM-nonMCI组间差异有统计学意义(P<0.05),右侧丘脑FA、KFA值在T2DM-nonMCI与T2DM-MCI组间差异有统计学意义(P<0.05)。此外,T2DM患者右侧丘脑FA、FAK值与MoCA评分呈正相关(r=0.328,P=0.015;r=0.435,P=0.001);左侧丘脑RK值与己酸浓度呈正相关(r=0.431,P=0.001);左侧丘脑MK值与MoCA评分及己酸浓度呈正相关(r=0.294,P=0.030;r=0.287,P=0.033);右侧丘脑FAK值与TMT-A评分之间呈负相关(r=-0.318,P=0.018)。结论 T2DM患者丘脑微观结构改变可能是引起认知障碍的重要生理机制,且肠道己酸含量或可在一定程度上影响左侧丘脑微观结构完整性。

糖尿病认知功能障碍病因病机制论框架研究

糖尿病认知功能障碍(diabetic cognitive dysfunction,DCD)是由糖尿病引发的中枢神经系统病变,是糖尿病常见的并发症之一,基于中医经典及各个医家著作,结合现代医学理论及实验进展,以中医基础理论为指导,深入研究与探索DCD病因病机,研究认为DCD的病位主要责之脾、心、肾三脏;并从脾、心、肾入手进行探讨,提出了脾不散精、浊毒伤络,心血不足、神明失所,肾精不足、脑髓失养等因机制论,疾病后期则因脏腑虚弱而导致痰浊、血瘀、脂毒等病理产物的形成。故该病以脏腑功能失调为本,痰浊、血瘀等病理产物为标,而这些病理产物又可以进一步损伤脏腑,该文就这种虚实夹杂的病情变化进行分析与阐明,讨论DCD的发病机制,以完善该病在中医理论体系的框架结构,为疾病的治疗提供理论基础。

基于AMPK/mTOR信号通路探讨中药复方益糖康对db/db小鼠血脑屏障通透性及紧密连接蛋白的影响

目的基于AMPK/mTOR信号通路,探讨中药复方益糖康对db/db小鼠血脑屏障通透性的影响及对紧密连接蛋白Occludin和ZO-1的调控作用。方法24只db/db小鼠随机分为模型组(db/db组)、利拉鲁肽组(LIRA组)以及益糖康组(YTK组),每组8只。另取8只db/m小鼠作为正常对照组(db/m组)。YTK组予以益糖康煎剂30 g·kg^(-1)·d^(-1)灌胃,LIRA组每日腹腔注射利拉鲁肽200μg·kg^(-1)·d^(-1),db/m组和db/db组给予等量蒸馏水灌胃。实验期间,对小鼠空腹血糖和体质量进行观察。给药6周后,通过Morris水迷宫任务和旷场实验对小鼠进行行为学检测;随后对小鼠进行处死取材,采用Elisa检测小鼠血脂相关指标,EB法观察小鼠血脑屏障通透性,Western blot法检测小鼠脑组织中AMPK/mTOR信号通路、紧密连接蛋白Occludin、ZO-1蛋白的表达情况。结果与db/m组比较,db/db组空腹血糖、血脂、体质量明显升高(P<0.05),逃避潜伏期和摸索距离显著增加,穿越次数和目标象限活动时间则明显减少,血脑屏障通透性明显增加(P<0.05),脑组织中AMPK、mTOR、Occludin、ZO-1蛋白的表达显著降低(P<0.05);与db/db组比较,YTK组小鼠血糖、血脂、体质量明显升高显著降低(P<0.05),逃避潜伏期和摸索距离显著下降,穿越次数和目标象限活动时间则明显增加,血脑屏障通透性明显降低,脑组织中AMPK、mTOR、Occludin、ZO-1蛋白的表达显著降低显著上调(P<0.05)。结论益糖康可能通过AMPK/mTOR信号通路,改善糖脂代谢情况,同时上调Occludin、ZO-1蛋白表达,从而保护BBB功能完整性,最终改善db/db小鼠认知功能障碍。

跑台运动对不同性别1型糖尿病小鼠代谢和慢性神经炎症的影响

背景:运动在糖尿病防治中已经得到广泛认可,有氧运动已经成为1型糖尿病治疗的重要组成部分之一,但是跑台运动对不同性别1型糖尿病代谢和慢性神经炎症的影响有待进一步探讨。目的:研究跑台运动对不同性别1型糖尿病小鼠代谢和慢性神经炎症的影响。方法:将40只C57BL/6小鼠按照性别分组为雄性组和雌性组,每组各20只,随后按照80 mg/kg连续注射链脲佐菌素3 d建立糖尿病小鼠模型。在雄性组和雌性组中各随机选取10只进行6周跑台运动设为糖尿病+运动组,另外10只设为糖尿病组。观察小鼠血清性激素、肝脏组织氧化应激、脑组织炎性因子、肝脏病理和Morris水迷宫检测行为学变化。结果与结论:(1)与糖尿病组相比,糖尿病+运动组延缓1型糖尿病小鼠的血糖升高(P<0.05),血清促卵泡激素、促黄体生成素、肝脏超氧化物歧化酶、丙二醛、脑组织肿瘤坏死因子α、白细胞介素6和白细胞介素1β水平明显下降(P<0.01),血清雌二醇、孕酮和雌激素和肝脏谷胱甘肽过氧化物酶蛋白显著升高(P<0.01,P<0.05)。(2)与雄性1型糖尿病小鼠相比,雌性1型糖尿病小鼠雌二醇水平显著较高,促黄体生成素水平较低(P<0.05)。(3)与雄性糖尿病+运动组小鼠相比,雌性糖尿病+运动组小鼠肝脏谷胱甘肽过氧化物酶水平低(P<0.05)。(4)与1型糖尿病组小鼠相比,运动训练小鼠的逃逸潜伏期持续更短(P<0.01);在雄性小鼠中,运动锻炼显著提升了1型糖尿病小鼠在目标象限所花的时间和平台穿越次数(P<0.01或P<0.05),在雌性小鼠中,运动锻炼显著提升了1型糖尿病小鼠在目标象限所花的时间(P<0.05)。(5)相关性分析表明,促卵泡激素、促黄体生成素、孕酮和超氧化物歧化酶、丙二醛、肿瘤坏死因子α、白细胞介素6和白细胞介素1β呈正相关(P<0.05或P<0.01),而雌二醇、孕酮与超氧化物歧化酶、丙二醛、肿瘤坏死因子α、白细胞介素6和白细胞介素1β呈负相关(P<0.05或P<0.01)。(6)上述结果证实,跑台运动对糖尿病小鼠代谢指标和慢性神经炎症调节的影响存在性别差异,性激素是跑台运动对糖尿病小鼠代谢、炎症和认知反应的一个重要变量。

中药治疗糖尿病认知障碍探析

目的:通过挖掘整理中医药治疗糖尿病认知障碍的相关文献,为临床和科研提供参考。方法:计算机检索中国知网、万方、维普、中国生物医学文献数据库等数据库中治疗糖尿病认知障碍的方药,运用Execl、SPSS 18.0软件对挖掘的中药进行药物频次、频率、性味归经及核心药对的分析。结果:共收集数据库中相关方药54首,涉及中药96味。出现频次前10味的药物依次为石菖蒲、茯苓、人参、熟地黄、川芎、丹参、山药、远志、甘草、黄连。四气以温、平、微温为主;五味以甘、苦、辛、酸为主;归经以肾经、脾经、肝经、心经、肺经、胃经为主。核心药对为川芎-当归、熟地黄-山茱萸、石菖蒲-山茱萸、石菖蒲-三七、川芎-枸杞子、熟地黄-枸杞子、山药-山茱萸、石菖蒲-山药、酸枣仁-远志-熟地黄、人参-丹参-石菖蒲、山药-丹参-石菖蒲。出现最多的药对为石菖蒲+补益药。结论:中医药治疗糖尿病认知障碍较西医存在一定的优势,具有疗效显著、价格低廉、操作简易、不良反应小等特点,治疗时多以补脾益肾、理气活血药物为主。

跑台运动通过p38 MAPK信号通路调控泛凋亡改善糖尿病小鼠认知功能障碍

认知功能障碍是2型糖尿病的严重并发症之一,运动干预改善糖尿病认知具有一定的疗效,但具体作用机制尚不清楚。本研究旨在探究跑台运动干预改善2型糖尿病小鼠认知功能障碍的作用及分子机制。取雄性8周龄m/m小鼠10只作为对照组,db/db小鼠40只随机分为4组,每组10只,分别为db/db组(模型组)、db+Exe组(运动组)、db+Exe+SB203580组(运动联合p38 MAPK抑制剂组)、db+SB203580组(p38 MAPK抑制剂组)。db+Exe组和db+Exe+SB203580组进行运动干预(40 min/次,5次/周,共8周);db+Exe+SB203580组和db+SB203580组在运动干预前2 h腹腔注射SB203580,(5 mg/kg,5次/周,共8周)。体重及空腹血糖测量结果显示,8周跑台运动干预可降低糖尿病小鼠体重及空腹血糖(P<0.01);水迷宫结果显示,跑台运动改善了糖尿病小鼠的认知功能障碍(P<0.05);免疫荧光染色结果显示,跑台运动降低了海马组织NLRP3的荧光强度,其中CA1区和CA3区具有显著性差异(P<0.05);跑台运动降低了海马组织PI的荧光强度,其中DG区具有显著性差异(P<0.01)。qRT-PCR结果显示,跑台运动降低了小鼠海马组织中IL-1β和IL-18 mRNA的表达,其中IL-1βmRNA的表达具有显著性差异(P<0.05);Western印迹结果显示,跑台运动减少了海马组织中凋亡相关蛋白质胱天蛋白酶3、胱天蛋白酶9和Bax的表达(P<0.01);降低了TXNIP(P<0.01)和焦亡相关蛋白质NLRP3、GSDMD-N、IL-1β、IL-18、切割胱天蛋白酶1和胱天蛋白酶1的表达(P<0.05);减少了坏死性凋亡相关蛋白质p-RIPK1、RIPK1、p-RIPK3、RIPK3的表达(P<0.05)。加入p38抑制剂后,跑台运动联合p38抑制剂干预更进一步地抑制了胱天蛋白酶3、TXNIP、GSDMD-N、IL-18的表达(P<0.05),胱天蛋白酶9、Bax、NLRP3、IL-1β、切割胱天蛋白酶1、胱天蛋白酶1的表达水平也呈现下降趋势;RIPK1、p-RIPK3的表达显著增加(P<0.05),p-p38、p-RIPK1、RIPK3的蛋白质表达水平呈上升趋势。综上所述,跑台运动干预可有效改善2型糖尿病小鼠的认知功能障碍,其作用机制部分是通过p38 MAPK信号通路调控细胞泛凋亡。

2型糖尿病患者前扣带回功能连接的静息态fMRI研究

目的:采用静息态f MRI探讨不伴轻度认知功能障碍(MCI)的2型糖尿病(T2DM)患者前扣带回功能连接(FC)的变化特点。方法:纳入56例T2DM及人口学资料相匹配的60例健康被试(HC),行静息态fMRI检查及神经心理学评估量表,以前扣带回不同亚区为种子点行全脑FC分析,将差异脑区的FC值与临床资料及神经心理学评分行相关性分析。结果:与HC相比,不伴MCI的T2DM患者膝前部前扣带回(pACC BA32)与双侧海马FC值减低,与双侧外侧前额叶及左侧中央前回FC值增高(P均<0.05)。T2DM组pACC(BA32)与左侧海马FC强度与颜色连线测试2(CTT-2)评分呈负相关(P=0.002,r=-0.410)。结论:不伴MCI的T2DM患者pACC(BA32)与双侧海马及双侧外侧前额叶FC紊乱,提示T2DM患者可能存在一种涉及记忆功能的代偿机制。

2型糖尿病伴脑小血管病相关认知功能障碍的MRI研究进展

认知功能障碍是2型糖尿病(T2DM)的常见并发症。脑微血管功能障碍是T2DM认知功能障碍的发病机制之一,脑小血管病(CSVD)是其主要表现形式。目前常采用MRI技术检测CSVD,包括常规MRI、扩散加权成像(DWI)、磁敏感加权成像(SWI)等。CSVD的MRI特征包括腔隙性梗死、脑白质高信号(WMH)、脑微出血(CMB)、血管周围间隙扩大(EPVS)、脑萎缩等,这些MRI特征与T2DM认知功能障碍密切相关。综述T2DM伴CSVD认知功能障碍的发病机制及MRI研究进展。

2型糖尿病患者血清GLP-1、Aβ1-42、MCP-1水平与认知功能障碍的相关性

目的 探究2型糖尿病(T2DM)患者血清胰高血糖素样肽-1(GLP-1)、β淀粉样蛋白1-42(Aβ1-42)、单核细胞趋化蛋白-1(MCP-1)水平与认知功能障碍的相关性。方法 分析2020年2月至2023年2月期间南京市江宁医院收治的102例T2DM患者的临床资料,根据蒙特利尔认知评估量表(MoCA)评分分为认知功能正常组(n=53)与认知功能障碍组(n=49)。比较两组患者血清GLP-1、Aβ1-42、MCP-1水平,并绘制ROC曲线评估上述指标单一及联合检测对T2DM患者出现认知功能障碍的预测价值。结果 两组GLP-1水平:认知功能正常组>认知功能障碍组,差异具有统计学意义(t=6.738,P<0.05)。两组血清Aβ1-42、MCP-1、FPG、HbA1 c水平:认知功能障碍组>认知功能正常组,差异均有统计学意义(t=6.042、8.255、3.985、2.259,P<0.05)。建立相关性模型,T2DM患者认知功能与GLP-1水平呈正相关(r=0.486,P<0.05),与Aβ1-42、MCP-1水平呈负相关(r=-0.558、0.601,P<0.05)。多因素Logistic回归分析显示,GLP-1、Aβ1-42、MCP-1是T2DM患者认知功能障碍的独立影响因素(P<0.05)。ROC曲线显示,GLP-1、Aβ1-42、MCP-1三者联合检测时,预测T2DM患者出现认知功能障碍的AUC为0.990,敏感性、特异性分别为0.910、0.952,优于单一检测(P<0.05)。结论 T2DM认知功能障碍患者血清MCP-1水平明显显著升高,Aβ1-42、GLP-1水平显著降低,三者联合检测可为T2DM患者预防认知功能损害提供重要的参考依据。