栀子苷对糖尿病模型大鼠认知功能障碍的改善作用研究

目的:研究栀子苷对糖尿病模型大鼠认知功能障碍的改善作用。方法:将50只大鼠随机分为空白对照组(蒸馏水)、模型组(蒸馏水)和栀子苷低、中、高剂量组(5、10、20 g/kg),每组10只。除空白对照组外,其余4组大鼠均饲以高糖高脂饲料+注射链脲佐菌素复制糖尿病模型。成模后,各组大鼠ig相应药物,每日1次,连续8周。末次给药后检测各组大鼠空腹血糖(FPG)、糖化血红蛋白(HbA_1c)水平,并检测Morris水迷宫实验的逃避潜伏期和Y迷宫实验的行为正确率。结果:与空白对照组比较,模型组大鼠FPG、HbA_1c水平明显升高,逃避潜伏期明显延长,Y迷宫行为正确率明显降低,差异均有统计学意义(P<0.05)。与模型组比较,栀子苷各剂量组大鼠上述指标均明显改善(P<0.05),且与剂量呈正相关(P<0.05)。结论:栀子苷可有效降低糖尿病模型大鼠血糖水平,改善其认知功能障碍。     

Exenatide对糖尿病大鼠认知功能的改善作用及机制研究

目的探讨Exenatide对糖尿病大鼠认知功能的改善作用及机制。方法SD大鼠随机分为正常组、糖尿病组(DM组)及Exenatide给药组(Ex+DM组)。Ex+DM组给药16周,水迷宫检测认知功能;电镜观察海马超微结构;检测与认知相关的p-tau(s202、s396)蛋白表达水平及氧化应激相关指标。结果与DM组比,Ex+DM组糖脂代谢、学习记忆能力、海马超微结构和氧化应激损伤改善,海马p-tau蛋白降低。结论Exenatide改善糖尿病大鼠认知功能,可能与改善糖脂代谢及海马氧化应激有关。     

精神分裂症伴发糖尿病患者认知功能损害的对照研究

目的:研究精神分裂症伴发糖尿病患者的认知功能损害情况.方法:采用mccb（精神分裂症认知功能成套测验共识版）评估精神分裂症伴发糖尿病患者的认知功能并与不伴发糖尿病的精神分裂症患者的认知功能进行对照研究.结果:伴发糖尿病的精神分裂症患者MCCB中的语义漉畅、言语记忆、视觉记忆、持续操作、迷宫、符号编码、数字序列较对照组存...     

非酶糖化抑制剂对糖尿病大鼠心肌细胞凋亡作用的研究

目的：观察非酶糖化抑制剂-氨基胍(AG)对糖尿病大鼠心肌细胞凋亡的影响。方法：54只SD大鼠分为12周对照组(8只)，24周对照组(10只)；糖尿病12周组(8只)，糖尿病24周组(10只)；AG治疗12周组(8只)，AG治疗24周组(10只)，观察糖尿病大鼠心肌病变过程中(12周及24周)心脏肥厚、心功能指标及心肌细胞凋亡的改变一结果：链尿佐菌素(STZ)诱导的糖尿病大鼠12周时出现心功能异常并可见凋亡的心肌细胞，随心衰的加重，24周时凋亡细胞数目明显增多。透射电镜检查，发现糖尿病大鼠左室心肌组织中可见凋亡的心肌细胞(具有凋亡形态学特征)。AG治疗组大鼠心功能和心肌超微结构明显改善，心肌细胞凋亡数目减少、结论：心肌细胞凋亡在糖尿病心肌病发生发展过程中起着重要作用，AG可有效减少心肌细胞凋亡，改善心肌病理形态学异常。     

白藜芦醇衍生物改善2型糖尿病大鼠血糖及胰岛素抵抗作用的研究

目的探讨白藜芦醇衍生物BTM-0512对2型糖尿病大鼠血糖及胰岛素抵抗作用的影响。方法单次腹腔注射链脲佐菌素（STZ,35mg·kg^-1）结合高脂饮食建立2型糖尿病大鼠模型。糖尿病大鼠分为3组（模型组、BTM-0512低剂量组、BTM-0512高剂量组）,药物灌胃3周。检测空腹血糖（FBG）、糖基化血红蛋白（HblAC）、空腹血清胰岛素（Fins）和口服糖耐量（OGTT）;计算HOME．IR、胰岛素敏感指数（1AD、胰岛素分泌指数（IS）,以此评价胰岛素抵抗（IR）。结果BTM-0512能剂量依赖性降低2型糖尿病大鼠FBG和HblAC,改善HOME．IR和IAI,但对OGTT与IS没有影响。结论BTM0512可以降低2型糖尿病大鼠血糖并改善IR。     

淫羊藿苷对精神分裂症模型大鼠认知功能的改善作用及机制

目的:研究淫羊藿苷(ICA)对精神分裂症模型大鼠认知功能的改善作用及机制。方法:将SD大鼠分为空白对照组、模型组和ICA低、中、高剂量组(15、30、60 mg/kg),除空白对照组外,其余组大鼠均腹腔注射N-甲基-D-天冬氨酸受体拮抗剂MK-801(0.2 mg/kg)复制精神分裂症模型,每天1次,连续14天。造模成功后,ICA各剂量组大鼠灌胃相应药物,空白对照组和模型组灌胃等体积水,每天1次,连续28天。采用Morris水迷宫实验、旷场实验、强迫游泳实验和Y迷宫实验观察大鼠行为学变化;采用Nissl法染色观察大鼠海马组织病理变化;采用酶联免疫吸附法(ELISA)检测大鼠脑组织中胆碱能相关指标[乙酰胆碱(Ach)、胆碱乙酰转移酶(ChAT)、乙酰胆碱酯酶(AchE)]的水平;采用实时荧光定量聚合酶链式反应(PCR)法检测大鼠脑组织中脑源性神经营养因子(BDNF)、细胞外信号调节蛋白激酶(ERK)、环磷腺苷反应元件结合蛋白(CREB)的mRNA的表达水平;采用Western blot法检测大鼠脑组织中BDNF、ERK、CREB蛋白和凋亡相关蛋白[B淋巴细胞瘤2(Bcl-2)及其相关X蛋白(Bax)、胱天蛋白酶3(Caspase-3)]的表达或磷酸化水平。结果:与空白组比较,模型组大鼠逃避潜伏期、T1~T3时段活动路程长度、累积不动时间和脑组织中Caspase-3蛋白的表达水平均显著增加或升高(P<0.05);穿台次数、交替率、海马组织中Nissl染色阳性神经元数以及脑组织中Ach和ChAT水平、Bcl-2/Bax比值、BDNF m RNA和蛋白的表达水平、ERK和CREB mRNA的表达水平、ERK1/2和CREB磷酸化水平均显著减少或降低(P<0.05)。与模型组比较,ICA高剂量组大鼠逃避潜伏期、T1~T3段活动路程长度、累积不动时间、Nissl染色阳性神经元数、脑组织中AchE水平和Caspase-3蛋白的相对表达量均显著减少或降低(P<0.05);穿台次数、交替率,脑组织中Ach和ChAT水平、Bcl-2/Bax比值、BDNF m RNA和蛋白的表达水平、ERK和CREB mRNA的表达水平、ERK1/2和CREB的磷酸化水平均显著增加或升高(P<0.05)。ICA低、中剂量组大鼠上述部分指标较模型组显著改善(P<0.05)。结论:ICA可改善精神分裂症模型大鼠的认知功能,其作用机制可能与调节胆碱能系统、抑制神经元凋亡、促进BDNF/ERK/CREB信号通路的表达有关。     

白藜芦醇对糖尿病及其并发症作用机制的研究进展

白藜芦醇是一种天然植物抗毒素,广泛存在于多种植物中。白藜芦醇对糖尿病及其并发症的药理作用机制多样,包括激活SIRT1和AMPK等增加胰岛素敏感性,改善胰岛素抵抗;激活Akt通路、增加GLUT2的表达以及抑制PDK,影响糖代谢进程降低血糖水平;激活SIRT1蛋白、PGC-1α蛋白以及参与线粒体途径,促进SOD1的生成、降低ROS的表达以及减少线粒体凋亡,减少胰岛β细胞的氧化应激损伤;也能通过激活AMPK通路、PPARα通路以及下调VEGF受体Flk-1的表达改善糖尿病肾病,抑制NF-κB而改善糖尿病性肝损伤和糖尿病视网膜病变等。综述了近5年来白藜芦醇对糖尿病及其并发症作用机制的研究进展,为进一步研究开发提供参考。     

白藜芦醇的生物学功能及作用机制

白藜芦醇又称芪三酚,是植物在遭受“逆境”时产生的一种植物抗毒素,属于非黄酮类的多酚化合物,广泛存在于自然界。白藜芦醇有顺、反2种结构,反式较顺式性质稳定、生理活性更强,在植物体内主要以反式构象存在,可以通过植物提取法、化学合成法、生物合成法等制得。白藜芦醇具有多种有益的生物学功能,引起了广大学者们的关注。研究发现,白藜芦醇具有抗氧化、抗炎、抗菌、抗病毒、抗肿瘤、免疫调节、调节糖脂代谢及抑制脂肪沉积、保护心脑血管系统等多种生物学功能。近年来,随着对白藜芦醇功能研究的深入,其在人类健康领域得到了广泛的应用。文章综述了白藜芦醇的理化性质、制备方法、所具备的生物活性及其作用机制,为白藜芦醇的研究与应用提供参考。     

白藜芦醇的生物学功能及作用机制

白藜芦醇又称芪三酚,是植物在遭受“逆境”时产生的一种植物抗毒素,属于非黄酮类的多酚化合物,广泛存在于自然界。白藜芦醇有顺、反2种结构,反式较顺式性质稳定、生理活性更强,在植物体内主要以反式构象存在,可以通过植物提取法、化学合成法、生物合成法等制得。白藜芦醇具有多种有益的生物学功能,引起了广大学者们的关注。研究发现,白藜芦醇具有抗氧化、抗炎、抗菌、抗病毒、抗肿瘤、免疫调节、调节糖脂代谢及抑制脂肪沉积、保护心脑血管系统等多种生物学功能。近年来,随着对白藜芦醇功能研究的深入,其在人类健康领域得到了广泛的应用。文章综述了白藜芦醇的理化性质、制备方法、所具备的生物活性及其作用机制,为白藜芦醇的研究与应用提供参考。     

Neuroprotective effects of resveratrol against intracerebroventricular colchicine-induced cognitive impairment and oxidative stress in rats

Alzheimer's disease is a complex and multifactorial neurodegenerative disease. Central administration of colchicine, a microtubule-disrupting agent, causes loss of cholinergic neurons and cognitive dysfunction that is associated with excessive free radical generation. The present study was aimed at evaluating the effects of trans-resveratrol in the prevention of colchicine-induced cognitive impairment and oxidative stress in rats. Intracerebroventricular administration of colchicine (15 microg/5 microl) induced impaired cognitive functions in both the Morris water maze task and the elevated plus-maze task. Chronic treatment with resveratrol (10 and 20 mg/kg, p.o.) for a period of 25 days, beginning 4 days prior to colchicine injection, significantly improved the colchicine-induced cognitive impairment. Intracerebroventricular colchicine injection resulted in free radical generation characterized by alterations in oxidative stress markers with a significant increase in malondialdehyde (MDA) and nitrite levels and depletion of reduced glutathione (GSH) activity in the rat brains. It also showed a significant decrease in acetylcholinesterase activity. Besides improving cognitive dysfunction, chronic administration of resveratrol significantly reduced the elevated MDA and nitrite levels and restored the depleted GSH and acetylcholinesterase activity. Results of the present study indicated that trans-resveratrol has a neuroprotective role against colchicine-induced cognitive impairment and associated oxidative stress.     

The effects of chronic resveratrol treatment on vascular responsiveness of streptozotocin-induced diabetic rats

Deficiency in the vasorelaxant capacity is a result of an oxidative stress in diabetic animals and seems to be an etiological factor of vascular complications of diabetes. The present study was designed to examine whether resveratrol (RSV), a polyphenolic compound which is naturally present in grape and red wine, has a protective effect on diabetic aorta. Resveratrol (5 mg/kg/d, i.p.) was administered for 42 d to streptozotocin (STZ) (60 mg/kg) induced diabetic rats. Loss of weight, hyperglycemia, and elevated levels of plasma malondialdehyde (MDA) were observed in diabetic rats. Resveratrol treatment was significantly effective for these metabolic and biochemical abnormalities. The contractile responses of the aorta were recorded. Compared with control subjects, the aorta showed significantly enhanced contractile responses to noradrenaline (NA), but not to potassium chloride (KCl), in diabetic rats. Treatment of diabetic rats with resveratrol significantly reversed the increases in responsiveness and sensitivity of aorta to noradrenaline. In diabetic aorta, the relaxation response to acetylcholine (Ach) was found to be significantly decreased compared with control subjects, and resveratrol treatment reversed this; no such change was observed in the relaxation response to sodium nitroprusside (SNP). These results indicated that resveratrol significantly improved not only glucose metabolism and oxidative injury but also impaired vascular responses in streptozotocin induced diabetic rats.     

Cerebroprotective effect of resveratrol through antioxidant and anti-inflammatory effects in diabetic rats

Oxidative stress and inflammation have been implicated in cerebral ischemia/reperfusion injury and complication of diabetes. The present study was designed to evaluate whether resveratrol has cerebroprotective action through antioxidant and anti-inflammatory actions in diabetic rats. Bilateral common carotid artery occlusion (30 min) and reperfusion (4 h) was employed to induce cerebral infarction in diabetic Wistar rats. Diabetes was induced by streptozocine (50 mg/kg) intraperitoneally at once. Diabetic animals were divided into groups as: normal, sham, ischemia–reperfusion, and resveratrol-treated (5, 10, 20, and 30 mg/kg). These were used for estimation of cerebral infarction. Furthermore, 20 mg/kg dose was selected for estimation of oxidative stress markers (malondialdehyde, superoxide dismutase, and catalase). Inflammatory markers like TNF-α, IL-6, IL-10, and myeloperoxidase were estimated and histological characters were studied. Resveratrol produced dose-dependent reduction in percent cerebral infarction. With resveratrol of 20 mg/kg dose, levels of oxidative stress markers and inflammatory markers like malondialdehyde, TNF-α, IL-6, and myeloperoxidase were reduced and there was a significant increase in the levels of antioxidant and anti-inflammatory markers like catalase, superoxide dismutase, and IL-10. In the present study, we found that mechanism(s) responsible for the cerebroprotective effect of resveratrol in the diabetic rat brain involves antioxidant and anti-inflammatory actions.     

认知功能训练改善轻度认知功能障碍的研究进展

阿尔茨海默病是最常见的神经系统退行性疾病之一,但其患者在达到痴呆症程度之前存在一定时期的轻度症状期,被称为阿尔茨海默病所致轻度认知功能障碍(mild cognitive impairment,MCI)阶段.不过,对MCI的治疗目前尚无统一的治疗原则或专家共识,且使用药物治疗MCI还存在一定的争议和风险.认知功能训练作为一种重要的非药物治疗手段,已逐渐成为早期干预认知功能减退的一种重要手段和研究热点.本文介绍对MCI患者进行认知功能训练的常用方式,具体论述了认知域和非认知域训练两种方法对MCI患者的认知功能和日常生活能力的影响,并讨论了认知功能训练效果的评估方法和训练设计的改良策略.     

Minocycline reverses diabetes-associated cognitive impairment in rats

BackgroundMinocycline a tetracycline antibiotic is known for anti-inflammatory and neuroprotective actions. Here we determine the therapeutic potential of minocycline against type 2 diabetes associated cognitive decline in rats.MethodsHigh fat diet (HFD) and low dose streptozotocin (STZ; 25 mg/kg) were used to induce diabetes in Sprague-Dawley rats. Fasting blood glucose and haemoglobin (Hb) A1c were measured in these animals. Cognitive parameters were measured using passive avoidance and elevated plus maze test. Hippocampal Acetylcholine esterase (AchE), reduced glutathione (GSH), cytokines, chemokine levels were measured and histopathological evaluations were conducted. The diabetic animals were then given minocycline (50 mg/kg; 15 days) and the above parameters were reassessed. MTT and Lactate dehydrogenase (LDH) assays were conducted on neuronal cells in the presence of glucose with or without minocycline treatment.ResultsWe induced diabetes using HFD and STZ in these animals. Animals showed high fasting blood glucose levels (>245 mg/dl) and HbA1c compared to control animals. Diabetes significantly lowered step down latency and increased transfer latency. Diabetic animals showed significantly higher AchE, Tumor necrosis factor (TNF)-α, Interleukin (IL)-1β and Monocyte chemoattractant protein (MCP)-1 and lower GSH levels and reduced both CA1 and CA3 neuronal density compared to controls. Minocycline treatment partially reversed the above neurobehavioral and biochemical changes and improved hippocampal neuronal density in diabetic animals. Cell line studies showed glucosemediated neuronal death, which was considerably reversed upon minocycline treatment.ConclusionsMinocycline, primarily by its anti-inflammatory and antioxidant actions prevented hippocampal neuronal loss thus partially reversing the diabetes-associated cognitive decline in rats.     

Beneficial effects of an Andrographis paniculata extract and andrographolide on cognitive functions in streptozotocin-induced diabetic rats

Context Andrographolide containing Andrographis paniculata (Burm. F.) Wall. Ex Nees (Acanthaceae) extracts is often used for treatments of diabetes and other inflammatory disorders commonly accompanying cognitive and other psychiatric disorders.

Objective To compare the efficacies of a standardised A. paniculata extract (AP) and pure andrographolide on cognitive functions, oxidative stress and cholinergic function in diabetic rats.

Materials and methods Streptozotocin-induced diabetic Charles Foster albino rats treated orally with a hydro-methanolic A. paniculata leaf extract (50, 100 and 200?mg/kg/day), or with pure andrographolide (15, 30 and 60?mg/kg/day) for 10 consecutive days, were subjected to Morris water maze test. After the test, acetylcholinesterase, superoxide dismutase (SOD), and catalase (CAT) activities and lipid peroxidation (LPO) in brain tissues were assessed.

Results Acetylcholinesterase activity in pre-frontal cortex and hippocampus of diabetic rats was 2.1 and 2.6 times higher compared to nondiabetic rats. LPO was 1.6 times higher and decreased SOD (56.3%) and CAT (44.9%) activities in pre-frontal cortex of diabetic rats compared to nondiabetic rats. AP or andrographolide treatments dose dependently attenuated cognitive deficits, reduced acetylcholinesterase activity, oxidative stress, improved diabetic hyperglycemia and insulin deficiency. All observed effects of AP were quantitatively almost equal to those expected from its analytically quantified andrographolide content.

Discussion and conclusion Reported observations are the very first ones suggesting beneficial effects of andrographolide against diabetes associated cognitive deficits, increased acetylcholinesterase activity and deteriorated antioxidative status. Efforts to exploit A. paniculata extracts enriched in andrographolide as preventive measures against such disorders can be warranted.     

The effects of galanin on neuropathic pain in streptozotocin-induced diabetic rats

Diabetic neuropathy is a common complication associated with diabetes and is frequently painful. However, mechanisms responsible for diabetic neuropathic pain are still unclear. Experimental evidence has shown that the galanin and its receptor are involved in pain sensitization. The objective of the present study was to investigate the role of galanin and its receptor antagonist or agonist on neuropathic pain in streptozotocin-induced diabetic rats. The expression of galanin, galanin receptors 1 and 2 in dorsal root ganglion (DRG) and spinal dorsal horn (SDH) in diabetic rats were detected by Western blot assay. The effects of galanin, galanin receptor antagonist M35, galanin receptor 1 agonist M617, and galanin receptor 2 agonist AR-M1896 on neuropathic pain were evaluated by mechanical stimuli. The results showed that (1) the diabetic rats showed a significant mechanical hyperalgesia between 4 and 12weeks; (2) galanin receptor 1 expression decreased in SDH in diabetic rats; (3) galanin receptor 2 expression decreased in DRG and SDH in diabetic rats; (4) intrathecal administration of exogenous galanin attenuated diabetic neuropathic pain, this effect could be blocked by pre-treatment with galanin receptor antagonist M35; and (5) intrathecal administration of galanin receptor 1 agonist M617, but not galanin receptor 2 agonist AR-M1896, attenuated diabetic neuropathic pain. These results imply that galanin acts through receptor 1, but not galanin receptor 2, to exert analgesic effect in diabetic neuropathic pain and is one of the potential therapeutic targets on diabetic neuropathic pain sensitization.     

利拉鲁肽对2型糖尿病轻度认知功能障碍患者炎性因子及认知功能的影响

目的：探讨利拉鲁肽对2型糖尿病轻度认知功能障碍患者炎性因子及认知功能的影响。方法：选取使用门冬胰岛素30治疗的2型糖尿病（T2DM）伴轻度认知功能障碍（MCI）患者86例，分为治疗组（43例）与对照组（43例），疗程1年。对照组维持原门冬胰岛素30治疗，治疗组改为利拉鲁肽治疗。治疗前和治疗12，24，36，48周末测定患者身高、体质量、血压水平，计算体重指数（BMI），并记录血糖达标[糖化血红蛋白（Hb A1c）≤ 8%]、低血糖情况、实验室检查（血糖、糖化血红蛋白、白细胞介素-1β（IL-1β）、白细胞介素-6（IL-6）、肿瘤坏死因子（TNF-α）水平），并采用简易精神状态量表（MMSE）、蒙特利尔认知量表（MoCA）评估认知功能。结果：对照组和治疗组各完成42例和41例。治疗12，24，36，48周末，治疗组IL-1β、IL-6、TNF-α水平显著低于对照组（P< 0.01），36，48周末HbA1c水平低于对照组（P<0.05），MMSE及MoCA量表评分高于对照组（P<0.05）。对照组和治疗组血糖达标率分别为76.19%（32/42）和82.93%（34/41），痴呆发生率均为0，差异均无显著意义（P>0.05）；低血糖发生率分别为59.52%（25/42）和7.32%（3/41），治疗组低于对照组（P<0.01）。结论：和门冬胰岛素30相比，利拉鲁肽治疗2型糖尿病MCI患者，能更好地控制FPG、2hPG、HbA1c，降低炎性因子水平（IL-1β、IL-6、TNF-α），低血糖发生率更低，并能改善患者认知功能。