葡萄糖对胰岛细胞胰腺-十二指肠同源盒基因-1表达的影响

目的 研究不同浓度葡萄糖对大鼠胰岛细胞胰腺-十二指肠同源盒基因-1(PDX-1)表达的调节作用.方法 用不同浓度葡萄糖分别刺激胰岛细胞1、4、7、14d,运用RT-PCR技术检测PDX-1基因表达的变化.结果 与对照组相比(葡萄糖浓度为5.5mmol/L),刺激胰岛细胞1d时,葡萄糖浓度为2.2mmol/L时,PDX-1表达显著降低,当葡萄糖浓度高于对照组时,PDX-1基因的表达量呈浓度依赖性升高;4d时,低糖浓度仍然显著抑制PDX-1基因表达,浓度升至11.1mmol/L,PDX-1基因表达量呈显著升高,浓度为16.7mmol/L时,PDX-1基因表达量呈下降趋势,浓度升至33.3mmol/L时,PDX-1基因表达量明显降低;7d时,除浓度11.1mmol/L外,其余浓度PDX-1基因表达均降低;刺激时间延长到14d,非生理浓度葡萄糖均表现为对PDX-1基因的抑制作用.结论 低血糖可以抑制PDX-1基因表达.短期的血糖升高可以一定程度地刺激PDX-1基因表达,但长期的高血糖则使PDX-1基因表达明显受抑.     

罗布麻叶水提取物对链脲佐菌素致糖尿病小鼠的治疗作用及对肠道GLP-1蛋白表达的影响

目的 探讨罗布麻叶水提取物（WEAVL）对链脲佐菌素（STZ）致糖尿病模型小鼠的治疗作用。方法 随机将ICR小鼠分为对照组和WEAVL（2.34 g/kg）组,每天ig给药1次,连续30 d,检测空腹血糖和体质量。ICR小鼠按200 mg/kg ip 2% STZ溶液制备糖尿病模型,造模成功的小鼠按血糖值随机分为模型组、盐酸二甲双胍（阳性药,130 mg/kg）组和WEAVL低、中、高剂量（0.58、1.17、2.34 g/kg）组,另设对照组,连续给药30 d,测定体质量、空腹血糖、糖耐量及血糖曲线下面积（AUC）;称取肝、肾质量,计算脏器系数;取胰腺组织进行HE染色、组织病理学检查;Western blotting检测肠道组织胰高血糖素样肽-1（GLP-1）蛋白的表达水平。结果 与对照组比较,单纯给予WEAVL对正常动物空腹血糖无明显影响,可显著降低小鼠体质量（P<0.01）。与对照组比较,模型组小鼠血糖显著升高（P<0.01）,各组小鼠体质量均显著降低（P<0.01）;与模型组比较,WEAVL高剂量组给药第2~4周体质量显著降低（P<0.05、0.01）,3个剂量组2 h血糖、血糖AUC均显著降低（P<0.01）,高剂量组肝脏系数显著降低（P<0.05）、肾脏系数显著升高（P<0.05）,中、高剂量组动物胰岛细胞空泡变性例数减少,中、高剂量组肠道组织GLP-1蛋白的表达显著上调（P<0.05）。结论 WEAVL对STZ致糖尿病小鼠有一定治疗作用,其作用机制可能与上调肠道组织中GLP-1的表达有关。     

雷公藤多甙对链脲佐菌素诱导糖尿病鼠胰岛α、β细胞的保护作用

为探讨雷公藤多甙对 I型糖尿病胰岛β细胞的保护作用 ,应用 SPTM免疫组织化学法检测糖尿病鼠胰岛α、β细胞。结果显示 ,T 治疗组鼠胰岛 β细胞的 AGV高于糖尿病组 ,而低于对照组 ;胰岛 α细胞结果与此相反。提示 T 可有效阻止免疫反应性细胞对胰岛 β细胞的破坏作用     

酮替芬对链脲佐菌素诱导的糖尿病模型大鼠胰岛功能的影响

目的:探讨酮替芬对链脲佐菌素诱导的糖尿病模型大鼠胰岛功能的影响及其作用机制.方法:以高糖高脂饲料对SD大鼠饮食诱导6周,随后一次性i.p.给予链脲佐菌素(STZ)制备糖尿病大鼠模型.模型建立后,实验组给予酮替芬0.09 mg·kg-1·d-1,分别在第0、4、8周宰杀实验大鼠,检测空腹血糖(FBG)、空腹胰岛素(FINS),计算胰岛素敏感指数(ISI)、胰岛素抵抗指数(HOMA-IR),检测炎症因子IL-6、TNF-α,并留取胰腺组织,制片染色进行光镜、电镜观察.分离胰岛细胞线粒体,检测细胞色素C氧化酶(Cytochrome C oxidase,CCO)、琥珀酸脱氢酶(Succinate dehydrogenase,SDH)活性.结果:酮替芬降低糖尿病大鼠的血糖水平(P＜0.05),增加ISI和降低HOMA-IR(P＜0.01),降低IL-6和TNF-α水平,增加胰腺组织中CCO和SDH活性(P＜0.01),还可以改善胰岛细胞形态结构.结论:酮替芬能改善糖尿病大鼠的胰岛功能,其作用机制可能是通过抑制NF-кB激活实现抗炎及改善β细胞线粒体的能量代谢.     

链脲佐菌素诱导1型糖尿病小鼠模型的研究

目的 探讨多次小剂量链脲佐菌素(MLD-STZ)诱导的1型糖尿病小鼠模型特点.方法 腹腔注射40 mg/kg体质量的STZ,每天1次连续5 d,观察小鼠血糖、尿糖及胰岛病理组织学改变.结果 模型制备成功率为65%,与正常对照组相比造模成功小鼠血糖、尿糖明显升高,有明显胰岛炎改变,且血糖自STZ末次注射后第4周至第8周一直维持在较高水平.结论 MLD-STZ腹腔注射能成功诱导1型糖尿病小鼠模型,且该模型血糖稳定时间较长.     

胰腺-十二指肠同源框-1与糖尿病的研究新进展

糖尿病是以胰岛素绝对或相对不足为主要特征的临床综合征,而胰岛素是由胰岛β细胞分泌的体内唯一降血糖激素。胰腺-十二指肠同源框-1(PDX-1)在胰腺的早期发育和晚期分化、胰岛β细胞正常功能的维持及胰岛素的分泌等方面均有重要作用。此外,PDX-1可诱导非胰岛细胞如肝细胞、成肌细胞等向胰岛素分泌细胞分化,提示PDX-1在糖尿病的治疗领域有重要作用。     

富硒木耳水提物对链脲佐菌素诱导的小鼠糖尿病肾损伤的保护作用

目的研究富硒木耳水提物(aqueous of Se-enriched Auricularia auricular,AESAA)对链脲佐菌素(streptozotocin,STZ)诱导的糖尿病肾损伤的保护作用及机制。方法给予小鼠高脂饮食联合STZ (80 mg·kg~(-1))建立糖尿病肾病(diabetic nephropathy,DN)模型。将60只C57B/6J小鼠随机分为空白组、模型组、二甲双胍组(metformin,Met,400 mg·kg~(-1))、AESAA低剂量组(500 mg·kg~(-1))、AESAA高剂量组(1 000 mg·kg~(-1))、普通木耳水提物组(aqueous extracts of Auricularia auricular,AEAA,1 000 mg·kg~(-1)),灌胃给药8周后,取血及肾脏组织。检测小鼠血清中总胆固醇(total cholesterol,TC)、甘油三酯(triglyceride,TG)、低密度脂蛋白(low density lipoprotein cholesterol,LDL-C)、尿素氮(blood urea nitrogen,BUN)、肌酐(creatinine,Cr)及尿酸(uric acid,UA)的含量;HE染色评价肾脏组织病理学变化;Western blot检测肾脏组织中高迁移率族蛋白1(high mobility group box 1 protein,HMGB1)、晚期糖基化终产物受体(the receptor of advanced glycation end products,RAGE)和核因子-κB(NF-κB)磷酸化的表达。结果与模型组相比,AESAA能改善肾脏病理性损伤;降低血清中TC、TG、LDL-C、Cr、BUN的含量(P<0.01)和UA的含量(P<0.05);抑制肾组织HMGB1、RAGE蛋白表达(P<0.01)和p-NF-κB蛋白表达(P<0.05)。结论 AESAA能逆转STZ诱导的糖尿病肾损伤,其机制可能与其调控HMGB1/RAGE/NF-κB信号通路有关。     

虎杖多糖对链脲佐菌素诱导糖尿病模型的降血糖作用研究

目的 研究虎杖多糖对链脲佐菌素诱导的糖尿病大鼠模型的降血糖作用。方法 采用水提醇沉法和乙醇提取两种方法提取并测定虎杖多糖的提取率;制备链脲佐菌素诱导的糖尿病大鼠模型,并给以虎杖多糖,观察对大鼠饮水量、排尿量、体重变化、空腹血糖、糖耐量的影响,分析链脲佐菌素诱导糖尿病模型动物一般情况、空腹血糖、口服糖耐量的变化。结果 乙醇提取法较水提醇沉法可显著提高虎杖多糖提取率;链脲佐菌素诱导的糖尿病模型组大鼠出现多饮、多食、多尿及体重减轻的现象;与模型组相比,虎杖多糖组大鼠饮水量、体重、排尿量有所改善,口服糖耐量及空腹血糖明显降低(P<0.05)。结论 虎杖多糖能够改善糖尿病大鼠“三多一少”的症状,显著降低糖耐量和空腹血糖,在糖尿病药物及保健食品的研究及开发中具有潜在的经济价值。     

链脲佐菌素诱导大鼠糖尿病肾病动物模型

随着世界各国社会经济的发展和居民生活水平的提高,糖尿病（DM）已成为继心血管病和肿瘤之后的第三大非传染病,其微血管并发症糖尿病肾病（diabetic nephropathy,DN）已成为终末期肾衰竭主要原因之一。由于DN发病机制尚未完全阐明,防治不完善,因此正确建立较理想的动物模型以深入研究是非常重要的。     

人工虫草对链脲佐菌素所致小鼠1型糖尿病的降糖作用及机制

目的:探讨人工虫草(蝙蝠蛾拟青霉人工发酵菌丝培养物,PHC)对小鼠1型糖尿病的降糖作用及机制。方法:采用少量多次腹腔注射STZ的方法建立1型糖尿病模型,观察药物对胰腺组织、血糖、肝脏SOD、LPO含量、血清IL-2和IL-10分泌以及小鼠脾T淋巴细胞增殖的影响。结果:低剂量PHC能明显降低糖尿病高血糖,升高血清SOD活力,降低LPO含量,且明显降低IL-2水平,抑制脾T淋巴细胞增殖反应。结论:低剂量PHC对STZ所致小鼠1型糖尿病有明显降糖作用,降糖机制与抑制T细胞应答或细胞因子对胰岛β细胞的破坏,以及清除自由基有关。     

诺和龙联合地特胰岛素治疗2型糖尿病的疗效观察

目的通过研究诺和龙联合地特胰岛素治疗继发性药物失效的2型糖尿病患者的治疗效果,为临床提供一种切实有效的治疗磺脲类药物继发性失效的方法。方法诺和龙每日3次口服,联合地特胰岛素每日睡前皮下注射(地特组,26例),诺和灵30R(诺和灵组,30例),分别于治疗前及治疗8周后检测HbA1C、FBG及2hPBG。结果两组治疗后指标均明显改善,差异有统计学意义(P<0.01)。地特胰岛素组HbA1C、FBG及2hPBG较治疗前明显改善,与诺和灵组治疗效果相同。结论使用诺和龙联合地特胰岛素对继发性药物失效的2型糖尿病患者非常安全,而且有明显疗效。     

格列美脲联合甘精胰岛素治疗2型糖尿病的疗效

目的:观察磺脲类药物继发性失效者联合甘精胰岛素治疗2型糖尿病的疗效及胰岛β细胞功能变化。方法:对磺脲类药物继发性失效患者改用格列美脲,睡前分别注射甘精胰岛素(甘精组,24例)、优泌林30R(优泌林组,30例),12周后比较两组血糖、糖化血红蛋白(HbA1c)以及血清C肽的变化。结果:两组血糖和HbA1c均有下降(P<0.01或P<0.05),治疗后C肽升高(P<0.05)。结论:联合甘精胰岛素治疗2型糖尿病有较好疗效,并有可能改善β细胞的功能。     

Efficacy and safety of sotagliflozin in treating diabetes type 1

Introduction: Sotagliflozin is the first dual SGLT1/SGLT2 inhibitor developed for use in diabetes. Sotagliflozin blocks SGLT2 in the kidneys and SGLT1 in the intestines resulting in reduced early phase glucose absorption and increased blood levels of GLP-1 and PYY. Urinary glucose excretion is lower than with other agents as a result of decreased glucose absorption. The primary development effort to date has been in Type 1 diabetes.

Areas covered: The published information on sotagliflozin is reviewed, along with the recent results of several pivotal Type 1 diabetes trials.

Expert opinion: Sotagliflozin treatment lowers HbA1c and reduces glucose variability, with a trend to less hypoglycemic events. In the Type 1 trials, sotagliflozin treated individuals experienced DKA at a higher rate than placebo treated patients. An additional safety issue arises from the as yet unknown potential risks in women of child bearing potential in whom DKA is of utmost concern. The sotagliflozin development program has now been extended to trials in Type 2 diabetes, and long term studies will be needed to assess the benefits and risks of the agent in comparison to other currently marketed SGLT2 inhibitors.     

贝前列素钠联合甲钴胺治疗老年2型糖尿病患者周围神经病变的疗效

目的 探讨贝前列素钠联合甲钴胺治疗老年2型糖尿病(T2DM)伴周围神经病变(DPN)的疗效.方法 老年T2DM伴DPN患者87例,在常规治疗基础上随机分为两组:A组44例,应用贝前列腺素钠联合甲钴胺治疗;B组43例,单用甲钴胺治疗.两组连续治疗14 d.观察临床症状、神经传导速度及不良反应.结果 A组总有效率为84.0%,高于B组的46.5%(P<0.01);A组部分尺神经、胫神经和腓总神经传导速度恢复优于B组(P<0.01).治疗过程中无明显不良反应.结论 贝前列素钠联合甲钴胺治疗老年T2DM伴DPN有效,无明显不良反应.     

Beneficial role of telmisartan on cardiovascular complications associated with STZ-induced type 2 diabetes in rats

We studied the effect of an eight-week treatment with telmisartan (5 mg kg(-1)day(-1)) on cardiovascular complications that are associated with type 2 diabetes in a neonatal rat model. Type 2 diabetes was induced by the administration of 90 mg/kg streptozotocin (STZ), ip, in two-day-old rats. The development of diabetes was checked 12 weeks after STZ administration, and the animals were divided into different groups. Telmisartan treatment was given for eight weeks. At the end of the eight-week treatment, various biochemical and cardiac parameters were measured. Diabetic rats exhibited hyperglycemia, hyperinsulinemia, hyperlipidemia, increased blood pressure and heart rate, increased creatinine, cardiac enzyme and C-reactive protein (CRP) levels, a reduction in the rate of pressure development and decay, cardiac hypertrophy and oxidative stress. Chronic treatment with telmisartan significantly prevented STZ-induced hypertension and tachycardia and elevated fasting glucose and insulin levels. It significantly prevented the dyslipidemia and significantly reduced the elevated creatinine and CRP levels and the levels of other cardiac enzyme markers, like lactate dehydrogenase and creatinine kinase, in diabetic rats. There was an increase in rate of blood pressure development and decay with telmisartan treatment. Telmisartan also produced beneficial effects by preventing cardiac hypertrophy, which was evident from left ventricular collagen levels, the cardiac hypertrophy index and the left ventricular hypertrophy index in diabetic rats. Telmisartan successfully prevented oxidative stress, which was evidenced by a decrease in malondialdehyde and an increase in glutathione, catalase, superoxide dismutase levels. In conclusion, our data suggest that telmisartan prevented STZ-induced metabolic abnormalities and cardiovascular complications in type 2 diabetes.     

Efficacy of N-methanocarbathymidine in treating mice infected intranasally with the IHD and WR strains of vaccinia virus

N-Methanocarbathymidine [(N)-MCT] is a newly identified inhibitor of orthopoxvirus replication in cell culture and in mice. Limited published animal studies indicated the compound is effective by intraperitoneal (i.p.) route at 10-100 mg/(kg day). More extensive studies using different treatment regimens in intranasally infected mice were conducted in order to further explore the potential of this compound compared to cidofovir in treating vaccinia virus infections. (N)-MCT was given twice a day for 7 days, whereas cidofovir was administered once a day for 2 days, each starting 24h after virus exposure for most experiments. (N)-MCT was not toxic up to 1000 mg/(kg day) by the i.p. treatment route. Oral and i.p. treatment regimens with (N)-MCT were directly compared during a vaccinia virus (IHD strain) infection, indicating that the nucleoside has good oral bioavailability in mice. Treatments by i.p. route with (N)-MCT (100 mg/(kg day)) reduced lung, nasal, and brain virus titers during an IHD virus infection, but not nearly to the same extent as i.p. cidofovir (100 mg/(kg day)). Treatment with both compounds decreased liver, spleen, and kidney virus titers, as well as reduced lung consolidation scores and lung weights. Onset of treatment could be delayed by 2 days with (N)-MCT and by 3 days with cidofovir, providing significant survival benefit during the IHD virus infection. Against a vaccinia virus (WR strain) infection in mice, i.p. (N)-MCT treatment prevented death at 500 mg/(kg day), which was comparable in activity to i.p. cidofovir (100 mg/(kg day)). Significant reductions in tissue virus titers occurred with both treatment regimens. (N)-MCT could be further pursued for its potential to treat orthopoxvirus infections in humans.     

香芹酚对STZ诱导的1型糖尿病小鼠糖脂代谢的影响

目的观察香芹酚对糖尿病小鼠糖脂代谢的影响。方法腹腔注射链脲佐菌素(streptozotocin,STZ)建立1型糖尿病C57BL/6小鼠模型,成模小鼠随机分成3组(糖尿病组、香芹酚10、20 mg·kg~(-1)低、高剂量组),以同周龄同性别正常小鼠为对照组。糖尿病组和对照组腹腔注射生理盐水,其余组每天腹腔注射香芹酚,每周测体重和随机血糖,分别在给药2、4、6周后处死,收集小鼠血清,检测血糖、血脂、血总胆固醇、肝功能指标。结果香芹酚可有效降低糖尿病小鼠的随机血糖、血脂和乳酸脱氢酶水平。结论香芹酚可降低1型糖尿病小鼠血糖、血脂,保护受损器官,对糖尿病及其并发症有一定的治疗作用。     

STZ引起的短期Ⅰ型糖尿病对大鼠背根神经节CGRP mRNA水平的影响

糖尿病时,感觉神经元和血浆中的降钙素基因相关肽(calcitonin gene-related peptides, CGRP)会发生改变,血管对CGRP的反应性减弱[1],CGRP的改变是糖尿病时疼痛增加和发生损伤性炎症的重要原因[2].但关于短期糖尿病状态下,CGRP mRNA的动态变化如何,尚无文献报道.本文着重探讨短期糖尿病背根神经节(dorsal root ganglion, DRG)中CGRP mRNA的早期动态变化.     

埃索美啦唑与法莫替丁联合治疗非糜烂性胃食管反流病

目的观察埃索美啦唑与法莫替丁联合治疗非糜烂性胃食管反流病（NERD）的疗效。方法86例NERD患者根据24h动态pH监测分为：阳性组及阴性组,各随机分为治疗组和对照组,治疗组清晨顿服埃索美啦唑40mg,夜间睡前服法莫替丁40mg,对照组仅清晨顿服埃索美啦唑40mg,两者均予西沙比利5mg,1日3次,疗程8周。治疗前及疗程结束后行胃镜检查,24h动态pH监测,观察其胃镜表现及反流症状的改善程度。结果阳性治疗组23例中治愈17例,有效5例,无效1例,总有效率95.7%,对照组23例中治愈10例,有效6例,无效7例,总有效率69.6%。阴性治疗组20例治愈8例,有效7例,无效5例,总有效率为75%,对照组20例治愈7例,有效5例,无效8例,总有效率为60%。结论埃索美啦唑与法莫替丁联合治疗NERDPH监测阳性的患者的疗效明显优于单用埃索美啦唑者（P〈0.05）,而对于PH阴性的患者无明显差异。     

二甲双胍对STZ诱导小鼠AD样症状的保护作用的研究

目的研究二甲双胍对侧脑室注射链脲佐菌素(STZ)所诱导的阿尔采末病(Alzheimers disease,AD)动物模型的保护作用。方法选用Morris水迷宫试验评估二甲双胍对STZ侧脑室注射诱导的AD动物模型的学习记忆能力的影响;采用蛋白免疫印迹法分析二甲双胍对AD动物模型脑内细胞骨架蛋白神经丝蛋白及Tau蛋白磷酸化的表达水平的影响。结果二甲双胍对链脲佐菌素侧脑室注射所诱导的AD模型小鼠的学习记忆能力有明显的改善作用。①Morris水迷宫:定位航行试验中,STZ组平均逃避潜伏期和路径长度较对照组明显增加,二甲双胍治疗组平均逃避潜伏期和路径长度较STZ组明显减少;空间探索试验中,STZ组穿越隐匿平台次数较对照组明显减少,二甲双胍治疗组穿越隐匿平台次数较STZ组明显增加(P均<0.05)。②Westernblot:与对照组相比,STZ组细胞骨架神经丝和tau蛋白的磷酸化较正常组表达明显增多,二甲双胍治疗组细胞骨架神经丝和tau蛋白的磷酸化较STZ组明显减少(P均<0.05)。结论二甲双胍可以改善小鼠阿尔采末病(AD)样的学习记忆能力的减退和早期细胞骨架的病理学改变。